Benzimidazole, benzothiazole and benzoxazole derivatives and use thereof as lta4h modulators

FIELD: chemistry.

SUBSTANCE: invention relates to inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), their enatiomers, racemates and pharmaceutically acceptable salts, as well as a pharmaceutical composition based on said inhibitors and method of treating, preventing or suppressing inflammation and other conditions which are mediated by activity of leukotriene A4-hydrolase. In general formula (II) , X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is O; Z is chosen from a group which consists of O and a bond; W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to the nitrogen atom which is bonded to the said W; R4 is chosen from a group which consists of H, OCH3 and Cl; R6 is H or F; and R2' and R3' are each independently chosen from a group which consists of: A) H, C1-7alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-7alkyl, where each of substitutes (A) is independently substituted with 0 or 1 RQ, where each of said RQ is a carbon atom substitute, which is at least one carbon atom, separate from nitrogen atom; B) HetRa substitute; C) -C1-7alkyl-C(O)Rx; H) -C0-4alkyl-Ar5, where Ar5 is a 5-member heteroaryl, which has one heteroatom, chosen from a group >NRY, and 0 or 1 additional heteroatom -N=, and optionally contains two carbonyl groups, and optionally benzo-condensed; I) -C0-4alkyl-Ar5' , where Ar5' is a 5-member heteroaryl, which contains 3 or 4 nitrogen atoms; M) SO2C1-4alkyl; alternatively, R2' and R3', taken together with a nitrogen atom with which they are bonded, form a heterocyclic ring which contains at least one heteroatom, which is the said bonded nitrogen atom, where the said heterocyclic ring is chosen from a group which consists of i) 4-7-member heterocyclic ring HetRb, where the said 4-7-member heterocyclic ring HetRb has one heteroatom, which is the said bonded nitrogen atom, and is substituted with 0, 1 or 2 identical or different substitutes, where the said substitutes are chosen from a group which consists of -RY, -CN, -C(O)RY, -C0-4alkyl-CO2RY, -C0-4alkyl-C(O)CO2RY, -C0-4alkyl-ORY, -C0-4alkyl-C(O)NRYRZ-, -C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY, -C0-4alkyl-NRYCO2RY, -C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4alkyl-NRWSO2RY, 1,3-dihydrobenzoimidazol-2-on-1-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol- 5-yl, -C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY, -C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, , ,; ii) 5-7-member heterocyclic ring HetRC which has one additional heteroatom separated from the said bonded nitrogen atom by at least one carbon atom, where the said additional heteroatom is chosen from a group which consists of O, S(=O)2 and >NRM, where the said 5-7-member heterocyclic ring HetRC has 0 or 1 carbonyl group and is substituted with 0, 1 or 2 substitutes at identical or different substituted carbon atoms, where the said substitutes are chosen from a group which consists of -C(O)RY and RZ; iii) one of 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl is substituted at the carbon atom by 0 or 1 substitute such as -C0-4alkyl-RZ, -C0-4alkyl-CO2RY; and iv) one of benzimidazol-1-yl, 2,8-diazospiro[4.5]decan-1-on-8-yl, 4-{[(2-tert-butoxycarbonylaminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 4-{[(2-aminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 9-yl-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid, 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl, and where substitute HetRa is a 6-member heterocyclic ring, with a carbon atom at the bonding site and contains a >NRM group as a heteroatom, where the said heteroatom is separated from the said carbon atom at the bonding site with at least 1 additional carbon atom; Rk is chosen from a group which consists of H and -C1-4alkyl; RL is chosen from a group which consists of -CO2RS; RS is hydrogen; RM is chosen from a group which consists of RZ, -C(O)RY; RN is chosen from a group which consists of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3 and NO2; RQ is chosen from a group which consists of -CN, -C0-4alkyl-ORY, -C0-4alkyl-CO2RY, -C0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY; RW is chosen from a group which consists of RY; RX is chosen from a group which consists of -ORY, -NRYRZ, -C1-4alkyl and -C1-4alkyl-RAr; RY is chosen from a group which consists of H, C1-4alkyl, -C0-4alkyl-RAr and -C0-4alkyl-RAr', each of which is substituted with 1 or 2 RN substitutes; RZ is chosen from a group which consists of RY, -C1-2alkyl-CO2RY ; RAr is a radical with a carbon atom at the bonding position, where the said radical is chosen from a group which consists of phenyl, pyridyl and pyrazinyl, where each carbon atom with permissible valence in each of the said groups is independently substituted with at least 0, 1 or 2 RN or 0 or 1 RL; RAr' is a 5-6-member ring which has 1 or 2 heteroatoms, chosen from a group which consists of O, S, N and >NRY, and has 0 or 2 unsaturated bonds and 0 or 1 carbonyl group, where each member with permissible valence in each of the said rings is independently substituted with 0 or 1 or 2 RK; Description is given of inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), a composition which contains these inhibitions, and their use for inhibiting activity of the LTA4H enzyme, as well as for treating, preventing or suppressing inflammation and/or conditions which are associated with such inflammation. In the said formula (I): X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is chosen from a group which consists of CH2 and O, W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to a nitrogen atom; R4 is chosen from a group which consist of H, OCH3, CI, F, Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently chosen from different groups.

EFFECT: new compounds have useful biological activity.

43 cl, 8 tbl, 12 dwg, 484 ex

 

The scope to which the invention relates.

The present invention relates to inhibitors of leukotriene A4-hydrolases (L4), used to treat inflammation. More specifically, the present invention relates to certain benzoxazol-2-ilen, benzothiazole-2-ilen and 1H-benzoimidazol-2-ilen compounds used as selective inhibitors of the enzyme L4 for the treatment of inflammatory conditions.

Prior art

Normally, inflammation is an overreaction of the immune system to invasion by microbial pathogens, exposure to chemicals or physical damage. However, in some cases, the inflammatory response can evolve into a chronic condition and cause an inflammatory disease. Therapeutic treatment of such chronic inflammation in various diseases is a serious health problem.

Leukotrienes (L) are biologically active metabolites of arachidonic acid (B. Samuelsson, Science 1983, 220(4597):568-575), which are involved in the development of inflammatory diseases, including asthma (D.A. Munafo et al., J. Clin. Invest. 1994, 93(3):1042-1050), inflammatory bowel disease (IBD)(P.Sharon & W.F. Stenson, Gastroenterology 1984, 86(3):453-460), chronic obstructive pulmonary disease (COPD) (P.J. Barnes, Respiration 2001, 68(5):441-448), arthritis (R.J. Griffiths et al., Proc. Natl. Acad. Sci., UA, 1995, 92(2):517-521; F. Tsuji et al., Life Sci. 1998, 64(3):L51-L56), psoriasis (K. Ikai, J. Dermatol. Sci. 1999, 21(3):135-146; Y.I. Zhu & M.J. Stiller, Skin Pharmacol. Appl. Skin Physiol. 2000, 13(5):235-245) and atherosclerosis (Friedrich E.B. et al., Arterioscler. Thromb. Vasc. Biol. 23, 1761-7(2003); K. Subbarao et al., Arterioscler. Thromb. Vasc. Biol. 24, 369-75 (2004); A. Helgadottir et al., Nat. Genet. 36, 233-9 (2004); Jala V.R. et al., Trends in Immun. 25, 315-322 (2004)). The leukotriene synthesis is initiated by the conversion of arachidonic acid to the unstable epoxide intermediate connection, leukotriene A4 (L4), under the action of 5-lipoxygenase (5-L) (A.W. Ford-Hutchinson et al., Annu. Rev. Biochem. 1994, 63:383-347). This enzyme is expressed predominantly by cells of myeloid origin, and in particular, neutrophils, eosinophils, monocytes/macrophages and mast cells (G.K. Reid et al., J. Biol. Chem. 1990, 265(32):19818-19823). L4 can be either anywhereman with glutathione under the action of leukotriene C4 (L4)-synthase with producing cysteinyl-leukotriene, L4 or hydrolyzed with the formation of the diol, leukotriene B4 (L4) (B. Samuelsson, Science 1983, 220(4597):568-575). L4 and its metabolites, LD4 and L4, induce contraction of smooth muscles, bronchostenosis and vascular permeability, and L4 is a strong chemoattractant and activator of neutrophils.

Stereospecific hydrolysis L4 education L4 catalyzed by leukotriene-A4-hydrolases (L4), zinc-containing cytosolic enzyme. This enzyme is expressed in all tissues, with high levels of E. what about the expression observed in the epithelial cells of the small intestine, in the lungs and in the aorta (B. Samuellson & C.D. Funk, J. Biol. Chem. 1989, 264(33):19469-19472). Moderate expression L4 observed in leukocytes, and in particular, neutrophils (T. Yokomizo et al., J. Lipid Mediators Cell Signaling 1995, 12(2,3):321-332).

Leukotriene B4 is a key proinflammatory mediator that promotes recruitment of inflammatory cells such as neutrophils and eosinophils, as well as activation of neutrophils (F.A. Fitzpatrick et al., Ann. N.Y. Acad. Sci. 1994, 714:64-74; S.W. Crooks & R.A. Stockley, Int. J. Biochem. Cell. Biol. 1998, 30(2):173-178; A. Klein et al., J. Immunol. 2000, 164:4271-4276). L4 mediates Pro-inflammatory effects by binding to receptors associated with G-protein, i.e. receptor leukotriene B4 (BLT1) 1 and the receptor for leukotriene B4 (BLT2) 2 (T. Yokomizo et al., Arch. Biochem. Biophys. 2001, 385(2):231-241). The first of the identified receptors, L1, associated with L4with high affinity, resulting in the production of the intracellular signal and chemotaxis. L1 is expressed mainly in peripheral leukocytes, and in particular, neutrophils, eosinophils, macrophages (W.W. Huang et al., J. Exp. Med. 188, 1063-74 (1998)) and monocytes (Yokomizo T. Izumi, T. & Shimizu, T. Life Sci 68, 2207-12 (2001)). Mouse receptor is also expressed on effector T cells and has recently been shown that it mediates L4dependent migration of effector CD8+-T-cells (Goodarzi K., Goodarzi M. Tager, A.M., Luster, A.D. & von Andrian, Uriah Heep show; Nat. Immunol, 4, 965-73 (2003), Ott, V.L., Cambier, J.C. Kappler, J., Marrack, P. ∓ Swanson, B.J. Nat. Immunol, 4, 974-81 (2003)) and early chemotaxis of effector CD4+-T cells-helper type 1 (TN1) and (TN2) and their adhesion to endothelial cells and early recruitment of effector CD4+- and CD8+-T-cells in animal models of asthma (A.M. Tager et al., Nat. Immunol, 4, 982-90 (2003)). L4-receptor L2 (S. Wang et al., J. Biol. Chem. 2000, 275(52):40686-40694; T. Yokomizo et al., J. Exp. Med. 2000, 192(3):421-431) has 42%homology with the receptor L1 in amino acid sequence, but detects a wider range of expression in tissues, including peripheral tissues such as spleen, ovary and liver, as well as in leukocytes. L2 associated with L4 with a lower affinity than L1, mediates chemotaxis at higher concentrations L4 and differs from L1 their affinity to some of the antagonists. Although antagonists of the receptor L4 can differ in their affinity to L1 and L2, however, it is expected that blocking the production of L4 using inhibitors L4 will lead to the suppression of subsequent events, mediated as L1 and L2.

Studies have shown that the introduction of exogenous L4 in normal tissue can induce inflammatory symptoms (R.D.R. Camp et al., Br. J. Pharmacol. 1983, 80(3):497-502; R. Camp et al., J. Invest. Dermatol. 1984, 82(2):202-204)). Elevated levels L4 was observed in various inflammatory diseases, including the gears, COPD, psoriasis, rheumatoid arthritis (RA), cystic fibrosis and asthma (S.W. Crooks & R.A. Stockley, Int. J. Biochem. Cell Biol. 1998, 30(2):173-178). Therefore, we can assume that the reduction in production L4 under the action of the inhibitor L4 activity will have a therapeutic effect on diseases of the wide range.

This idea is confirmed by research conducted on L4-deficient mice models, which, if not observed full recovery, still showed a noticeable reduction in the influx of neutrophils into the area of the ear inflammation induced by arachidonic acid, and in the area of peritonitis induced zinasanam (RS Byrum et al., J. Immunol. 1999, 163(12):6810-6819). In preclinical studies it has been shown that inhibitors L4 are effective anti-inflammatory agents. So, for example, oral administration of an inhibitor L4 S57461 led to the inhibition induced by ionophores production L4 in the blood of miceex vivoand in the peritoneum of ratsin vivo(J.K. Kachur et al., J. Pharm. Exp. Ther. 2002, 300(2), 583-587). After 8-week treatment with the same connection-inhibitor showed a significant reduction in symptoms of colitis in Oedipus Tamarin (marmoset) (T.D. Penning, Curr. Pharm. Des. 2001, 7(3):163-179). Spontaneous colitis that developed in these animals is very similar to IBD in humans. Therefore, these results indicate that the inhibitor is L4 must have a therapeutic effect on the disease and other inflammatory diseases.

Events, inducing an inflammatory response include the formation of Pro-inflammatory mediator leukotriene B4. Hydrolase L4 catalyzes the production of this mediator, and inhibitors L4 block the production of Pro-inflammatory mediator L4 to prevent state-mediated leukotriene, such as inflammation, and/or conduct their effective treatment. The inflammatory response is characterized by pain, fever, redness, swelling or reduction of tissue functions, or combinations of two or more of these symptoms. As for the start and the subsequent development of inflammation, inflammatory diseases or mediated inflammation diseases or conditions include, but are not limited to, acute inflammation, allergic inflammation and chronic inflammation.

Description inflammation of the subjects can be found, for example, in: J.I. Gallin & R. Snyderman, Inflammation: Basic Principles and Clinical Correlates, 3rd Edition (Lippincott Williams & Wilkins, Philadelphia, 1999); V. Stvrtinova, J. Jakubovsky & I. Hulin, “Inflammation and Fever”, Pathophysiology Principles of Diseases (Textbook for Medial Students, Academic Press, 1995); Cecil et al., In Textbook Of Medicine, 18thEdition (W.B. Saunders Company, 1988) and Steadmans Medical Dictionary.

The known data and the review of available data related to inflammation and associated with inflammation conditions can be found in the following papers: C. Nathan, Points of control in inflammation, ature 2002, 420:846-852; K.J. Tracey, The inflammatory reflex, Nature 2002, 420:853-859; L.M. Coussens & Z. Werb, Inflammation and Cancer, Nature 2002, 420:860-867; P.Libby, Inflammation in atherosclerosis, Nature 2002, 420:868-874; C. Benoist &D. Mathis, Mast cells in autoimmune disease, Nature 2002, 420:875-878; H.L. Weiner & D.J. Selkoe, Inflammation and therapeutic vaccination in CNS diseases, Nature 2002, 420:879-884; J. Cohen, The immunopathogenesis of sepsis, Nature 2002, 420:885-891; D. Steinberg, Atherogenesis in perspective: Hypercholesterolemia and inflammation as parthers in crime, Nature Medicine 2002, 8(11):1211-1217. All cited in the present description of work put into the form of a link.

Inflammation is caused by any of a variety of conditions such as asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), or psoriasis, each of which is characterized by heavy or prolonged inflammatory reaction at certain stages of this disease.

The authors have obtained benzoxazol-2-silt, benzothiazole-2-ilen and 1H-benzoimidazol-2-ilen compounds and their derivatives, and found that they can be used as inhibitors of enzyme activity, such as enzyme L4 involved in the production of proinflammatory mediators, such as the mediator L4, and that they can also be used to treat inflammatory conditions and pharmaceutical compositions for treatment of inflammation.

The description of the things the spine inventions

The present invention relates to inhibitors of the enzyme L4, which have the following General formula (I):

where:

X is selected from the group consisting of NR5, O and S, where R5represents one of N and CH3;

Y is selected from the group consisting of CH2and;

Z is selected from the group consisting of O and communication;

W is selected from the group consisting of CH2and R1-CH2where R1represents H or HE, and where associated with R1carbon group in the specified R1-CH2not directly linked to the nitrogen atom is linked to the specified W;

R4selected from the group consisting of H, och3, Cl, F, Br, I, HE, NH2, SP, CF3and CH3;

R6represents H or F; and

R2and R3each independently selected from the group consisting of:

A) H, C1-7of alkyl, C3-7alkenyl, where the carbon atom at the specified alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom in the specified quinil, which is linked to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; -C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl and phenyl, where each of the substituents (a) independently Zam is converted to 0, 1 or 2, RQwhere each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;

C) Deputy tRand;

C) -C1-7alkyl-C(O)Rx, optionally substituted CH2RAror CH2RAr';

D) -C2-5alkyl-C(O)Rxwhere two carbon atoms with a valid valence b-C2-5the alkyl specified With2-5alkyl-C(O)or SIGxare part saturated With3-6carbocycle;

E) -C2-5alkyl-HE, where two carbon atoms with a valid valence b-C2-5the alkyl specified With2-5alkyl-C(O), IT is part saturated With3-6carbocycle;

F) -C0-4alkylphenyl, where phenyl in the specified-C0-4alkylphenyl fused with Rfon two adjacent carbon atoms in the specified phenyl, or is benzododecinium;

G) -C0-4alkyl-AG6where Ar6represents a 6-membered heteroaryl, which has a carbon atom at the connection point and one or two-N= heteroatoms, and is benzododecinium;

N) -C0-4alkyl-AG5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group consisting of O, S and >NRYand 0 or 1 additional heteroatom-N=, and not necessarily the soda is separated by two carbonyl groups, and optional benzododecinium;

I) -C0-4alkyl-AG5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom, optionally substituted RYand is permitted by the valency of the position of the connection;

J) -C0-4alkyl-AG6-6where Ar6-6represents a C0-4alkyl-substituted phenyl condensed with 6-membered heteroaryl in allowed by valency position where the specified 6-membered heteroaryl has one or two-N= heteroatoms;

K) -C0-4alkyl-AG6-5where Ar6-5represents a C0-4alkyl-substituted phenyl, fused with 5-membered heteroaryl in allowed by valency positions where the specified 5-membered heteroaryl has one heteroatom selected from the group consisting of O, S and >NRYand where specified 5-membered heteroaryl has 0 or 1 additional heteroatom, which is-N=,

L) one 2-(4-ethylenoxy)benzothiazole, 2-(4-ethylenoxy)benzoxazole and 2-(4-ethylenoxy)-1H-benzoimidazole,

M) SO2With1-4of alkyl;

and alternative, R2and R3taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is attached to the nitrogen atom, where the aforementioned heterocyclic ring selected from g is PI, consisting of

i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY, -CN, -C(O)RY- 0-4alkyl-CO2RY,

-C0-4alkyl-C(O)CO2RY- 0-4alkyl-or SIGY- 0-4alkyl-C(O)NRYRz-,

-C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY- 0-4alkyl-NRYC(O)CH2ORY,

-C0-4alkyl-NRYC(O)CH2C(O)RY- 0-4alkyl-NRYCO2RY,

-C0-4alkyl-NRYC(O)NRYRY- 0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY,

-NRYRZ- 0-4alkyl-NRWSO2RY1,3-dihydroindol-2-on-1-yl,

1,3-dehydrobenzperidol-2-on-1-yl, tetrazol-5-Il,

1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-Il,

pyrrolidin-2-tion-1-yl, piperidine-2-tion-1-Il,

-C0-4alkyl-C(O)N(RY)(SO2RY)- C0-4alkyl-N(RY)(SO2)NRYRY,

-C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, ,,and;

ii) a 5-7 membered heterocyclic ring HetRwithhaving one additional heteroatom separated from the specified attached nitrogen, at least one carbon atom, where the specified additional heteroatom selected from the group consisting of O, S(=O)0-2and >NRMwhere specified 5-7-membered heterocyclic ring tRWithis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RY, -CO2RY- 3-4alkyl-CO2RYand RZ;

(iii) one of imidazolidin-1-yl, 2-imidazolin-1-yl, pyrazole-1-yl, imidazol-1-yl, 2H-tetrazol-2-yl, 1H-tetrazol-1-yl, pyrrol-1-yl, 2-pyrrolin-1-yl and 3-pyrrolin-1-yl, where each of these 2N-tetrazol-2-yl and 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as -With0-4alkyl-RZ- 0-4alkyl-SRY- 0-4alkyl-CO2RYand Deputy HetRa; and

iv) one of the 1,2,3,4-tetrahydroquinolin-1-Il,

1,2,3,4-tetrahydroisoquinoline-2-yl, indol-1-yl, isoindole-2-Il,

indolin-1-yl, benzimidazole-1-Il,

2,8-diaza-Spiro[4.5]Decan-1-one-8-Il,

4-{[(2-tert-butoxycarbonylamino balanceball)amino]methyl}piperidine-1-Il,

4-{[(2-aminocyclohexanol)amino]methyl}piperidine-1-Il,

9-Il-tert-butyl ether 3,9-diaza-Spiro[5.5]undecane-3-carboxylic acid,

4-oxo-1-phenyl-1,3,8-triaza-Spiro[4.5]Dec-8-yl, and

4-oxo-1,3,8-diazaspiro[4.5]Dec-8-yl,

where the Deputy HetRandis a 4-7-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas heteroatom, where said heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;

RKselected from the group consisting of H, -C1-4of alkyl, -C0-4alkyl-RAr, each of which is optionally substituted by 1, 2 or 3 substituents RN;

RLselected from the group consisting of-CO2RSand-C(O)NRSRS';

RMselected from the group consisting of RZ, indol-7-yl, -SO2RY- 3-4alkyl-CO2RY, -CO2RY, -C(O)NRZORY-C(O)RY-C(O)0-4alkyl-or SIGY- 0-4alkyl-C(O)NRSRS'- 0-4alkyl-C(O)CO2RY1,3-dihydroindol-2-on-1-yl, 1,3-dehydrobenzperidol-2-on-1-yl, tetrazol-5-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-yl-s0-4alkyl-C(O)N(RY)(SO2RY), each of which is optionally substituted , 2 or 3 substituents RN;

RNselected from the group consisting of co3, Cl, F, Br, I, OH, NH2CN, CF3CH3, OC(O)CH3and NO2;

RRselected from the group consisting of RY- 2-4alkyl-or SIGY, RAr- 1-2alkyl-CO2RY- 1-2alkyl-NRSRS', indol-7-yl and-SO2With1-4of alkyl;

RQselected from the group consisting of fluorine, chlorine, bromine, iodine, trifloromethyl, trichloromethyl, -CN, -C1-4of alkyl, -C0-4alkyl-RAr- 0-4alkyl-RAr'- 0-4alkyl-or SIGY- 0-4alkyl-CO2RY- 0-4alkyl-NRYRY- 0-4alkyl-NRYCORY- 0-4alkyl-NRYCONRYRZ- 0-4alkyl-NRYSO2RYand-C0-4alkyl-SRY;

RSand RS'independently selected from the group consisting of H, C1-4the alkyl and C0-4alkylphenyl; alternatively, RSand RS'taken together with the nitrogen atom to which they are bound, form a 4-7-membered heterocyclic ring having 0 or 1 additional heteroatom, selected from the group consisting of O, S and >NRYprovided that the additional heteroatom is separated from the nitrogen atom, which is associated with the specified RSand RS'at least two carbon atoms, and provided that the EU is and R Yrepresents-C0-4alkyl-RY, RArnot substituted RL;

RWselected from the group consisting of RYand C3-7cycloalkyl;

RXselected from the group consisting of-or SIGY, -NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;

RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1, 2 or 3 substituents RN;

RZselected from the group consisting of RY- 2-4alkyl-or SIGY- 1-2alkyl-CO2RY- 1-2alkyl-C(O)NRSRS'and-C2-4alkyl-NRSRS';

moreover, if RYand RZlinked to the nitrogen atom, the RYand RZselected as defined above, or RYand RZtaken together with the nitrogen atom to which they are bound, form a 4-7-membered heterocyclic ring HetRdhaving 0 or 1 additional heteroatom, selected from the group consisting of O, S and >NRMwhere specified 4-7-membered heterocyclic ring HetRdis 0 or 1 carbonyl group, and where the specified 4-7-membered heterocyclic ring HetRdhas 0 or 1 carbon atom with a valid valence, substituted, at least one of RM, -CO2H and-C0-1alkyl-or SIGY;

RArthe present is the focus of a radical, having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, pyridyl, pyrimidyl and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0, 1, 2, or 3 RNor 0 1 or RL;

RAr'is a 3-8-membered ring has 0, 1 or 2 heteroatoms selected from the group consisting of O, S, N and >NRYand is 0, 1 or 2 unsaturated communication and 0 or 1 carbonyl group, where each member with a valid valence in each of these rings is independently substituted by 0 or 1 or 2 RTo; and

Rfis a linear 3-to 5-membered hydrocarbon group having 0 or 1 unsaturated carbon-carbon bond and a is 0 or 1 carbonyl group;

or their enantiomers, diastereomers, racemates, tautomers, hydrates, solvate or pharmaceutically acceptable salts, esters or Amida.

In one embodiment, the present invention relates to new compounds which are inhibitors of LTA4H enzyme, and which have the General formula (II):

or their enantiomers, diastereomers, racemates, tautomers, hydrates, solvate or pharmaceutically acceptable salts, esters or Amida,

where R4, R6, X, , Z and W are as defined for compounds of formula (I), R2'is the same as R2in the compound of formula (I), and R3'is the same as R3in the compound of formula (I), provided that:

(a) at least one of the R2'and R3'is not ethyl when one of the combinations (s1), (s2), (s3) and (s4), where each of these combinations is defined as follows:

(s1): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents S;

(s2): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents NH;

(s3): R4represents N, Z represents O, W represents CH2, Y is Oh, and X represents S;

(s4): R4represents 5-chloro, Z represents O, W represents CH2, Y is CH2and X represents S;

(b) further provided that when Z is a bond, Y is CH2W represents R1-CH2, R1represents H and one of R2'and R3'represents 1H-imidazol-2-yl, any of the R2'and R3'selected from A1),)-L), where-L) identified above for soedineniya (I), and A1) consists of H, C3-7alkenyl, where the carbon atom at the specified3-7alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom in the specified quinil, which is linked to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl, and

(C) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2'and R3'is not CG if the other represents C1-6alkyl, where XCG is a group:

where HC16 represents one of H, C1-6of alkyl, halogen-C1-6of alkyl, allyl and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup (>N-C(O)-) with the nitrogen atom to which is attached the GO.

In other embodiments, the present invention relates to new compounds which are inhibitors of LTA4H enzyme and have the General formula (III):

or their enantiomers, diastereomers, racemates, tautomers, hydrates, solvate the iLike their pharmaceutically acceptable salts, esters or Amida where:

R4, R6X, Y, Z and W are as defined for compounds of formula (I), R2”is the same as R2in the compound of formula (I), and R3” is the same as R3in the compound of formula (I), provided that:

(a) the R2”and R3”, further satisfy one of the following conditions:

(E1): at least one of the R2”and R3”isn't C1-5the alkyl when Z represents O, and X represents S;

(E2): none of the R2”and R3”is not-C1-4alkyl-C(O)RXwhere RXrepresents one of the1-4of alkyl, HE, -OS1-4of alkyl, -OS0-4alkyl-RAror-NRYRYif Y is O, Z is a bond, and R2”differs from R3”; and

(E3) none of R2”and R3”is not-C1-4alkyl-SP, if Y is O, Z is a bond, and R2”differs from R3”; and

(b) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2”and R3”is not XCG, if the other represents C1-6alkyl, where XCG is a group:

where HC16 represents one of H,C 1-6of alkyl, halogen-C1-6of alkyl, allyl and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup (>N-C(O)-) with the nitrogen atom to which is attached the GO.

Isomeric forms of the compounds of the above formula and their pharmaceutically acceptable salts, amides and esters are included in the scope of the present invention, and cited in this description link to one of such isomeric forms include at least one of these isomeric forms. The person skilled in the art it will be obvious that the compounds of the present invention can be, for example, in one isomeric form, and other compounds can exist in the form of a regioisomeric mixture.

It should be noted that in any part of the description and claims, each definition of the Deputy and member of the structure in the context of the present invention is independent of the definition of another structure member and Deputy, unless otherwise stated. As a first example of terminology definitions of the substituents can be considered the following conditions: if the Deputy S1exampleis one of S1and S2and Deputy S2exampleis one of S3and S4such op is adelene substituents, included in the scope of the present invention, means the following options: S1examplerepresents the S1and S2examplerepresents the S3; S1examplerepresents the S1and S2examplerepresents the S4; S1examplerepresents the S2and S2examplerepresents the S3; S1examplerepresents the S2and S2examplerepresents the S4; and equivalents of each of these options. In accordance with that used in this description to more abbreviated terminology “S1examplerepresents one of the S1and S2and S2examplerepresents one of the S3and S4” merely for the sake of brevity, and should not be considered as limiting the scope of the invention. First the example above, the terminology used to designate deputies, which is a General term that refers to the described definitions of the various substituents R. the Above terminology is adopted to denote substituents extends to other groups, if they are present, for example, such as X, Y, Z and W, and the index n.

In addition, if for any element of the structure or Deputy is more h is m one definition, the variants of the present invention include various combinations of groups that can be made on the basis of the above definitions are made independently of each other, and their equivalents. As a second example terminology definitions of the substituents may be considered following conditions: if the Deputy S1exampleis one of S1, S2and S3such definitions of the substituents included in the scope of the present invention, means the following options: Sexamplerepresents the S1; Sexamplerepresents the S2; Sexamplerepresents the S3; Sexamplerepresents one of the S1and S2; Sexamplerepresents one of the S1and S3; Sexamplerepresents one of the S2and S3; Sexamplerepresents one of the S1, S2and S3; and Sexampleis any equivalent of each of these options. In accordance with that used in this description to more abbreviated terminology “Sexamplerepresents one of the S1, S2and S3” are given only for the sake of brevity and should not be considered as limiting the scope of the invention. First the example above, the terminology used to refer to substituents that PR is dstanley a General terminology refers to describe the definitions of the various substituents R. the Above terminology is adopted to denote substituents extends to other groups, if they are present, such as, for example, X, Y, Z and W, and the index n.

Item Ci-j”where j>i, if she applies for a class of substituents, is used only for those variants of the present invention, in which independently are all atoms and each carbon atom denoted i-j, including i and j. For example, the term1-3independent means options that have one atom of carbon (C1); options, which have two atoms of carbon (C2and options that have three atoms of carbon (C3).

The termn-malkyl means a straight or branched aliphatic chain, where the total number (N) of carbon atoms of the chain satises the conditions n≤N≤m, where m>n.

If any value relating to the Deputy, member of the connection or to the index occurs more than once, then the full interval of definition means that it applies to every object, regardless of the particular(s) determine(s)assigned to another object.

With regard to the above interpretations, definitions and nomenclature, in this connection, it should be noted that the specific instructions in this description reference to determine elenoa multiple values, if it relates to chemical symbols, and unless otherwise stated, means independent reference so many options, and a link to each one of the possible subsets of the specified precisely specified set.

The present invention also relates to methods of inhibiting the activity of LTA4H enzyme using such compounds, to pharmaceutical compositions containing such compounds, and to methods of using such compositions for the treatment or prevention of conditions mediated by the enzymatic activity of LTA4H.

The pharmaceutical compositions of the present invention include at least one of the compounds of the present invention. If the composition is included in more than one of these compounds, therapeutically effective amount can be an effective additive amount. As such, enzyme inhibitors L4 can be used compounds and compositions of the present invention, intended for the prevention, suppression or treatment of inflammation.

The present invention also relates to pharmaceutical compositions for the treatment and prevention of indirect L4 state of a subject, which comprises a therapeutically effective amount of at least one L4 modulator selected from compounds of formula (I), (II) and (III), their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, amides and esters. In addition, the present invention relates to pharmaceutical compositions for inhibiting an immune response in the subject, and containing a therapeutically effective amount of at least one inhibitor L4 selected from compounds of formula (I), (ii) and (III), their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, amides and esters. The present invention also relates to anti-inflammatory compositions containing a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formula (I), (ii) and (III), their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, amides and esters.

The present invention relates to methods of treating or preventing inflammation in a subject, introducing this subject a pharmaceutical composition comprising a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formula (I), (ii) and (III), their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, amides and esters, for generating the subject an anti-inflammatory response is. The present invention also relates to methods of treating or preventing L4-mediated condition in a subject, introducing this subject a pharmaceutical composition comprising a therapeutically effective amount of at least one modulator L4 selected from compounds of formula (I), (ii) and (III), their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, amides and esters. In addition, the present invention relates to a method of suppressing inflammation in the subject, introducing this subject a pharmaceutical composition comprising a therapeutically effective amount of at least one inhibitor L4 selected from compounds of formula (I), (ii) and (III), their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, amides and esters.

The present invention relates to methods for treating, preventing and/or attenuating conditions that are associated with inflammation and/or inflammation, such as, for example, one or more of the following conditions: asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease (including Crohn's disease and ulcerative colitis) or psoriasis, each of which is characterized with the school or prolonged inflammatory reaction at certain stages of this disease.

Other distinctive features and advantages of the present invention will be apparent from the following description, including the examples and the below claims.

Detailed description of the invention

The present invention relates to compounds of formula (I), (ii) or (III), defined above, to their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, Amida and esters; to pharmaceutical compositions containing at least one of these compounds, to methods of their use, including the treatment and/or prevention of conditions such as L4-mediated condition, and to methods of producing such pharmaceutical compositions.

The following are definitions of terms used in the description.

“Alkyl” means a hydrocarbon with straight and branched chain, from which removed, at least one hydrogen atom with the formation of radical groups. Alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, 1-methylpropyl, pentyl, isopentyl, sec-pentyl, hexyl, heptyl, octyl etc. These alkyl groups do not include cycloalkyl.

“Alkenyl” means hydrocarbon radicals, straight and branched chain mentioned above, which have at least one carbon-carbon double bond (sp2). If not is speaking specifically, the prefix indicates the number of carbon atoms, and examples of alkenyl are ethynyl (or vinyl), prop-1-enyl, prop-2-enyl (or allyl), Isopropenyl (or 1-methylvinyl), but-1-enyl, but-2-enyl, butadienyl, pentenyl, hexa-2,4-dienyl etc.

“Quinil” means hydrocarbon radicals, straight and branched chain mentioned above, which have at least one carbon-carbon triple bond (sp). Unless otherwise noted, the specified prefix indicates the number of carbon atoms, and examples of alkinyl are ethinyl, PROPYNYL, butynyl and pentenyl. In the present description, hydrocarbon radicals, having a mixture of double and triple links, such as 2-penten-4-inyl, belong to the group of alkinyl.

“Alkoxy” means a hydrocarbon alkyl group with straight and branched chain having a terminal oxygen, alkyl linking group with the remainder of the molecule. Alkoxygroup are methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, intoxi etc. Group “aminoalkyl”, “thioalkyl and sulfonylated” are analogous alkoxy, except that the terminal oxygen atom of alkoxygroup replaced, respectively, NN (or NR), S and SO2.

Unless otherwise stated, the prefix indicates the number of carbon atoms. Examples of “cycloalkyl are cyclopropyl, cyclobutyl, cyclopent is l, cyclohexyl, cycloheptyl, cyclooctyl etc.

Unless otherwise stated, the prefix indicates the number of members in this cyclic structure, and examples of “heterocyclyl”, “heterocyclic group” or “heterocycle” are 3-8-membered aromatic, saturated or partially saturated single or condensed ring system containing carbon atoms, where the heteroatoms selected from N, O and S. Examples heterocyclyl are thiazolyl, furyl, pyranyl, isobenzofuranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolin, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, indolyl, indazoles, purinol, chinolin, furutani, pyrrolidinyl, pyrrolyl, imidazolidinyl, imidazolyl, pyrazolidine, pyrazoline, piperidyl, piperazinil, indolinyl and morpholinyl. For example, the preferred heterocyclyl or heterocyclic radicals are morpholinyl, piperazinil, pyrrolidinyl, pyridyl, cyclohexylamino, cycloheptylamine, and more preferred is piperidyl.

The position of substitution is determined by the standard terms. For example, the position of substitution in piperidinol and piperazino groups listed below:

“Carbocycle” is cycloalkyl or partially saturated cycloalkyl, which is not I who is benzo

The term “aryl” includes phenyl, naphthyl, biphenylyl, tetrahydronaphthyl and the like, each of which may be optionally substituted. “Aryl” also means arylalkyl groups such as benzyl, phenethyl and phenylpropyl. “Aryl” includes ring system containing optionally substituted 6-membered carbocyclic aromatic ring, where this system can be bicyclic, bridged and/or condensed. Such a system may include rings that are aromatic, or partially or completely saturated. Examples of ring systems include indenyl, pentalene, 1,4-dihydronaphtho, indanyl, benzimidazolyl, benzothiophene, indolyl, benzofuranyl, ethenolysis etc. Illustrative examples of heteroaryl are thienyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, benzothiazyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzothiazolyl.

The term “halogen” includes chlorine, fluorine, bromine and iodine, preferably fluorine or chlorine.

The term “carbonyl” means a group >C=O, and is characterized part of a chain or a cyclic structure, where the carbon atom in the carbonyl group is taken as one of the carbon atoms of this chain or cyclic structure.

As in standard chemical nomenclature, in the present description, the phenyl group is called “phenyl” and is marked “RH”.

It should be noted that unless otherwise stated, the terms “replacement” and “combinations of substitution” means the replacement, which correspond to the valence of the substituted member. The terms “position permitted by valence”, “atom with a valid valence” and their morphological variants used in the present description in their conventional sense. For example, if the term “valid valency” refers to the carbon atom, I mean, what is tetravalent; if this term refers to the nitrogen atom, we mean that N is trivalent, and if this term refers to the four relations of nitrogen atom, then this means that the nitrogen atom has a positive electric charge. The definition of a valid valence are part of the competence of a person skilled in this field.

The terms “patient” or “subject” includes mammals, such as humans and animals (e.g. dogs, cats, horses, rats, rabbits, mice, and primates, non-human)in need of observations, experiments, treatment or prevention of the relevant disease or condition. Preferably, the patient is the man.

The term “composition” means a product that contains specific ingredients in the specified amounts of the Ah, including an effective amount of, as well as any product that is obtained, directly or indirectly, from combinations of the specified ingredients in the specified amounts.

The terms “therapeutically effective amount” or “effective amount” and their grammatical forms refer to the number of active compound or pharmaceutical agents that produce biological or clinical response in a tissue system, animal or human body, which is provided by the researcher, veterinarian, physician or other Clinician, where the response includes the weakening of the symptoms of the disease or disorder being treated.

Table abbreviations
The termThe acronym
TetrahydrofuranTHF
N,N-dimethylformamideDMF
N,N-dimethylacetamideDMA
The sulfoxideDMSO
Tert-butylcarbamoylVOS
Bovine serum albuminSA
High performance liquid chromatographyHPLC
Thin-layer chromatographyTLC

Compounds of formula (I), (ii) or (III)are compounds that satisfy any of the below combinations of definitions and cash equivalents.

It should be noted that some of the described compounds are compounds having chiral and/or geometric isomeric centres, for example, E - and Z-isomers. The present invention covers all of these optical isomers, including diastereoisomeric and racemic mixtures, geometric isomers, possessing a activity that characterizes the compounds of the present invention. In addition, some of the described compounds may exist in solvated, and resolutional form. It should also be noted that the present invention includes all of these solvated and nonsolvated forms with activity, which characterizes the compounds of the present invention. Compounds of the present invention, which has been modified so that they could be detected by some analytical methods, are also included in the scope nastojasih the invention. Examples of such compounds are labeled with isotopes of compounds such as a compound labeled with an isotope18F, which can be used as a probe in methods of detection and/or imaging, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). Another example of such compounds is isotope labeled compound, such as labeled with deuterium and/or tritium compound that can be used in studies of the kinetics of the reaction.

It should also be noted that the described substitutions and combinations of substitutions, regardless of whether it is direct or indirect indication, refer to substitutions that correspond to the valence of the substituted atom. For example, if the substitution is applied to the carbon atom, we mean that this is tetravalent, if the substitution is applied to the nitrogen atom, we mean that N is trivalent, and if it refers to the four relations of nitrogen atom, then this means that the nitrogen atom has a positive electric charge. The definition of a valid valence are part of the competence of a person skilled in this field.

The term “pharmaceutically acceptable salts, amides or esters” means salts, amides and esters of the compounds of this image is the shadow and clear any chemist-pharmacist that is, the term refers to compounds that are non-toxic and attach the specified compounds of the present invention is favorable pharmacological properties. The term “compounds of the invention with favorable pharmacological properties clear to any chemist, pharmacist, that is, it means compounds that are non-toxic and possess pharmacological properties, acceptable taste, good absorbiruyaci, the desired tissue distribution and the desired parameters of metabolism and excretion. Other factors that are more important from a practical point of view, and which should be considered when choosing these compounds are the cost of the starting materials, ease of crystallization, yield, stability, hygroscopicity, and the fluidity of the medicine mass.

Typical acids and bases that can be used to obtain pharmaceutically acceptable salts, are the following acids: acetic acid, 2,2-dichlorsilane acid, an acetylated amino acid, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzolsulfonat acid, benzoic acid, 4-acetamidobenzoic acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-Sultonova the acid, capric acid, Caproic acid, Caprylic acid, cinnamic acid, citric acid, ciclamino acid, modellerna acid, ethane-1,2-disulfonate acid, econsultancy acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galacturonic acid, gentisic acid, glucoheptonate acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, α-oxoglutarate acid, glycolic acid, hippuric acid, Hydrobromic acid, hydrochloric acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DL-mandelic acid, methanesulfonate acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonate acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamula acid, phosphoric acid, L-pyroglutamyl acid, salicylic acid, 4-aminosalicylic acid, sabotinova acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, titanova acid, p-toluensulfonate acid and undecylenoyl acid; and

these bases, including ammonia, L-arginine, benethamine, benzathine, hydroxide calcium, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)ethanol, ethanolamine, Ethylenediamine, N-methylglucamine, geranamine, 1H-imidazole, L-lysine, magnesium hydroxide, 4-(2-hydroxyethyl)morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)pyrrolidine, secondary amine, sodium hydroxide, triethanolamine, tromethamine and zinc hydroxide.

See, for example, the work of S.M. Berge et al. “Pharmaceutical Salts”, J. Pharm. Sci. 1977, 66:1-19, which is introduced in the present description by reference. Suitable examples of esters are1-7alkilany,5-7cycloalkenyl, phenyl, substituted phenyl and phenyl-C1-6alkilany esters. Preferred esters are methyl esters.

In the scope of the present invention also includes prodrugs of the compounds of the present invention. Usually such prodrugs can be functional derivatives of the compounds, which are easily converted to the desired compoundin vivo. For example, in the treatment methods of the present invention, the term “introduction” includes the treatment of various described conditions using the described specific compounds or compounds that are not specifically described, but which, after their introduction to the patient, can turn into this particular connectionin vivo. Standard methods for the selection and obtaining suitable proletarienne derivative is written, for example, in “Design of Prodrugs”, ed. H. Bundgaard, Elsevier, 1985.

Join some of the variants of the present invention, where X represents O, obtained by the synthesis methods presented in schemes A-D and F-L, have L4-inhibitory activity and is selected from the group consisting of the following compounds.

ExampleConnection
112-[4-(2-piperidine-1-ylethoxy)phenoxy]benzooxazol;
13(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
141-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
16{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dibutylamine;
21(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
271-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
281-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol;
29 2-[4-(2-piperidine-1-retil)phenoxy]benzooxazol;
35{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclohexylethylamine;
361-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}piperidine-4-ol;
401-{3-[4-(benzooxazol-2-yloxy)phenoxy]-2-hydroxypropyl}-4-phenylpiperidine-4-ol;
41ethyl ester of 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
442-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzooxazol;
45{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}dimethylamine;
46{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dimethylamine;
472-[4-(2-azepin-1 ylethoxy)phenoxy]benzooxazol;
531-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
54{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
552-{4-[2-(2-stor is piperidin-1-yl)ethoxy]phenoxy}benzooxazol;
561-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-carbonitrile;
571-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)Etalon;
582-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}benzooxazol;
591-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
601-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
611-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
621-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
63{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
64{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine;
65{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}butylethylamine;
66 2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}benzylamino)ethanol;
672-{4-[2-(4-benzylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol;
68(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol;
692-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}propylamino)ethanol;
772-[4-(2-azetidin-1 ylethoxy)phenoxy]benzooxazol;
78N-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
79ethyl ester of 1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
862-{4-[3-(4-phenylpiperazin-1-yl)propoxy]phenoxy}benzooxazol;
881-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
89{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
902-[4-(2-pyrrolidin-1-retil)phenoxy]benzooxazol;
91 2-[4-(2-azepin-1-retil)phenoxy]benzooxazol;
92{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
93{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}dibutylamine;
941-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
96methyl ester 1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1161-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}-4-phenylpiperidine-4-ol;
1202-[4-(3-pyrrolidin-1-ylpropyl)phenoxy]benzooxazol;
121{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}dibutylamine;
122{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclopropanemethylamine;
1351-[4-(benzooxazol-2-yloxy)phenoxy]-3-pyrrolidin-1-improper-2-ol;
1361-[2-(4-benzooxazol-2-ylmethylene)ethyl]-4-phenylpiperidine-4-ol;
137 amide 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2712-(4-piperidine-1-ylmethylene)benzooxazol;
4812-[4-(2-morpholine-4-ylethoxy)phenoxy)benzooxazol and
484{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}diethylamine.

Join other variants of the present invention, where X represents S, obtained by synthesis methods, are presented on figures A-G and I-L, have L4-inhibitory activity and is selected from the group consisting of the following compounds.

td align="left"> 3-[5-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)tetrazol-1-yl]propionitrile;
ExampleConnection
12{2-[4-(6-chlorobenzothiazole-2-yloxy)phenoxy]ethyl]diethylamine;
151-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
17ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
181-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
19(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-1-ylmethanone;
20ethyl ester of 3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
22amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
231-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
241'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he;
258-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2,8-diaza-Spiro[4.5]Decan-1-he;
262-[4-(3-pyrrolidin-1 ipropose)phenoxy)benzothiazole;
30{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
31amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
321-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-methyl-1,3-dehydrobenzperidol-2-he;
33methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
34(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-(4-methylpiperazin-1-yl)methanon;
42methyl ether of 1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
433-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)propionic acid;
48{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dimethylamine;
492-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzothiazole;
50{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}dimethylamine;
512-[4-(2-azepin-1 ylethoxy)phenoxy]benzothiazole;
522-[4-(2-azepin-1 ylethoxy)phenoxy]-6-methoxybenzothiazole;
701-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
71{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}College militiamen;
721-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
73{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dibutylamine;
741-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
751-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
761-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol
801'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipiperidine;
81(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
82N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
831'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he;
842-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethoxy}phenoxy)benzothiazole;
852-4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethyl}phenoxy)benzothiazole;
871-{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
951-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
972-[4-(2-pyrrolidin-1-retil)phenoxy]benzothiazole;
982-[4-(2-azepin-1-retil)phenoxy]benzothiazole;
99{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
100{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}dibutylamine;
1012-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1021-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-4-ol;
103methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
104amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
105ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carbon is th acid;
106ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-carboxylic acid;
107ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
1081-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dihydroindol-2-he;
1091-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)pyrrolidin-2-he;
110N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-2-phenylacetamide;
1118-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-2,8-diaza-Spiro[4.5]Decan-1-he;
1121-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-ol;
113ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1141'-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-[1,4']bipiperidine;
1152-{4-[2-(4-methylpiperazin-1-yl)ethyl]phenoxy}benzothiazole;
1432-(4-{2-[4-(1-benzyl-1H-tetrazol-5-yl)piperidine-1-yl]ethoxy}phenoxy)benzothiazole;
144tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-carboxylic acid;
1462-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethyl}phenoxy)benzothiazole;
147amide 1-[2-(4-{benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
1481-{1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-yl}pyrrolidin-2-he;
1491-[4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-yl]Etalon;
1501-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1511-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-tion;
1522-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)ethanol;
1532-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-who irreligion-1-ylatason;
1542-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
1551-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1561-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-2-carboxylic acid;
157(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)acetic acid;
158ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
159tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)carbamino acids;
160(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
161(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)methanol;
162methyl ether ({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylamino)acetic acid;
163(4-{2-[4-(benzothiazol-2-yl) - Rev. XI)phenoxy]ethyl}piperidine-1-yl)acetic acid;
164ethyl ester of 1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
1661-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
1674-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
168N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-chloro-N-cyclopropanesulfonyl;
1703-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine)propionic acid;
1713-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}isopropylamino)propionic acid;
1721-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ylamine;
1733-[{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-(1-methylpiperidin-4-yl)amino]propionic acid;
1743-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}benzoylamino)propionic acid;
1753-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}amino)propionic acid;
176tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)piperidine-1-carboxylic acid;
1773-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionic acid;
1783-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)propionic acid;
1793-[{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}(1 methylpiperidin-4-yl)amino]propionic acid;
1803-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propionic acid;
1813-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-isopropylamino)propionic acid;
1822-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
183(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
184 1-(1-[2-(4-benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dehydrobenzperidol-2-he;
1852-(4-{2-[4-(6-methylpyridin-2-yl]piperazine-1-yl]ethyl}phenoxy)benzothiazole;
1862-{4-[2-(4-acanaloniidae-1-yl]ethyl]phenoxy}benzothiazole;
1872-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
1883-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)propionic acid;
1893-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopentylamine)propionic acid;
1903-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclobutylamine)propionic acid;
1923-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}benzoylamino)propionic acid;
193(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-(4-hydroxyethylpiperazine-1-yl)methanon;
194{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
195 (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperazine-1-yl]metano;
196(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperidine-1-yl]metano;
1972-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)ethanol;
1983-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-1-ol;
1994-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
2003-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
2014-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyronitrile;
2023-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)propionic acid;
203[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
2043-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-the l)phenol;
2052-(4-{2-[4-(4-methoxyphenyl)piperazine-1-yl]ethoxy}phenoxy)benzothiazole;
2062-{4-[2-(5-piperidine-4-intersol-1-yl)ethoxy]phenoxy}benzothiazole;
207(S)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
208{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl;
209ethyl ester of 2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarboxylic acids;
210ethyl ester of 4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-carbonyl)benzoic acid;
2112-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarbonyl acid;
2121-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-2-ol;
2133-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-1,1,1-tryptophan-2-ol;
214 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionamide;
2153-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propane-1,2-diol;
2162-{4-[2-(5-phenyltetrazol-2-yl)ethoxy]phenoxy}benzothiazole;
2172-{4-[2-(5-phenyltetrazol-1-yl)ethoxy]phenoxy}benzothiazole;
218N-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N-cyclopropyl-2-(2H-tetrazol-5-yl)ndimethylacetamide;
219(S)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
220(R)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
2212-{4-[2-(5-methylsulfonylmethyl-2-yl)ethoxy]phenoxy}benzothiazole;
2222-{4-[2-(5-methylsulfonylmethyl-1-yl)ethoxy]phenoxy}benzothiazole;
2232-[4-(2-tetrazol-2-ylethoxy)phenoxy]benzothiazole;
2242-[4-(2-tetrazol-1 ylethoxy)phenoxy]benzothiazole;
225(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
226(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
227(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
228(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
2294-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)butyric acid;
2501-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
2511-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-he;
2522-(2-fluoro-4-piperidine-1-ylmethylene)benzothiazole;
253N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetate;
2541-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-he;
2551-1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide;
2562-{4-[4-(1H-tetrazol-5-yl)piperidine-1-ylmethyl]phenoxy}benzothiazole;
2571-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane;
258N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide;
2593-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-he;
2604-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one;
261(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
2622-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
263(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
264ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
265ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
266hydrochloride of 2-{4-[2-(5-piperidine-4-intersol-2-yl)ethoxy]phenoxy}benzothiazole;
2677-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]-4-Spiro[3-phtalic]piperidine;
268ethyl ester of 1-{3-[4-(benzothiazol-2-yloxy)phenyl]propyl}piperidine-4-carboxylic acid;
269hydrochloride of 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine;
2702-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethoxy]phenoxy)benzothiazole;
2712-(4-piperidine-1-ylmethylene)benzooxazol;
272[4-(benzothiazol-2-yloxy)benzyl]cyclohexylethylamine;
273[4-(benzothiazol-2-yloxy)benzyl]cyclopropanemethylamine;
274amide 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
2751'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipyridinyl-2-he;
276{4-[4-(benzothiazol-2-yloxy)b is nil}piperazine-1-yl}pyridine-3-ylmethanone;
277tert-butyl ether ({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbamino acids;
278methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbamino acids;
279tert-butyl ether N-{C-[[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl]methylaminomethyl}carbamino acids;
280the hydrochloride of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}sulphonamide;
281N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}ndimethylacetamide;
282{1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-yl}acetic acid;
283({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbarnoyl)methyl ester acetic acid;
284tert-butyl ether [2-({1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-ylmethyl}carbarnoyl)cyclobutyl]carbamino acids;
285the dihydrochloride {1-[4-(benzothiazol-2-yloxy)benzyl]Piperi the Jn-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acid;
2862-(4-pyrrolidin-1 ylmethylene)benzothiazole;
2872-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}ethanol;
2882-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-2-yl}ethanol;
2891-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}Etalon;
2908-[4-(benzothiazol-2-yloxy)benzyl]-2,8-diaza-Spiro[4.5]Decan-1-he;
291Spiro[isobenzofuran-1(3H), 4'-piperidine]-3-one, 1'-[4-(benzothiazol-2-yloxy)benzyl]
292(R)-1-[4-(benzothiazol-2-yloxy)benzyl]pyrrolidin-3-ol;
2932-[4-(2-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
294[4-(benzothiazol-2-yloxy)benzyl]diethylamine;
295[4-(benzothiazol-2-yloxy)benzyl}butylmethylamine;
2962-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ethanol;
2971-[4-(is isothiazol-2-yloxy)benzyl}piperidine-4-ol;
298{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-2-yl}methanol;
299(R)-{1-[4-(benzothiazol-2-yloxy)benzyl]pyrrolidin-2-yl}methanol;
3002-(4-azetidin-1 ylmethylene)benzothiazole;
3011-[4-(benzothiazol-2-yloxy)benzyl]-[1,4]diazepan-5-he;
302{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-3-yl}methanol;
303amide 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-3-carboxylic acid;
304tert-butyl ester 9-[4-(benzothiazol-2-yloxy)benzyl]-3,9-diaza-Spiro[5.5]undecane-3-carboxylic acid;
3052-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-3-yl}ethanol;
306triftoratsetata salt of CIS-4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarboxylic acids;
307(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
308 (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amide propane-2-sulfonic acid;
309methyl ester of (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acids;
310triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)benzosulfimide;
311triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)methanesulfonamide;
312triftoratsetata salt (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acids;
313(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)morpholine-4-ylmethanone;
3141-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-thiophene-2-ylatason;
315(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-3-ylmethanone;
316(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)cyclopropylmethanol;
3171-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-methoxyethanol;
3181-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2,2,2-triptoreline;
3194-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-carbonyl)benzoic acid;
320(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-4-ylmethanone;
321(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(5-methylpyrazine-2-yl)methanon;
322(R)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
323(S)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
324(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-3-yl)methanon;
3251-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-hydroxyethane;
3262-[2-(4-{2-[4-(benzothiazol the-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-oxoethyl]Cyclopentanone;
327triftoratsetata salt of 3-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)propionic acid;
3283-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)oxazolidin-2-he;
3294-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)morpholine-3-one;
3304-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)morpholine-3-one;
3313-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)oxazolidin-2-he;
332benzylacetone 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
333(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
334(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
335hydroxyamide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
336(S)-1-(1-{2-[-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
337tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbamate acids;
3382-{4-[2-(4-foreperiod-1-yl)ethyl]phenoxy}benzothiazole;
3392-{4-[2-(4,4-deformability-1-yl)ethyl]phenoxy}benzothiazole;
340(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}pyrrolidin-3-ol;
341N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)formamide;
342(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)urea;
3431-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-phenylazomethine;
3441-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylisoleucine;
345N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methanesulfonamide;
3461-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylguanine;
3478-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1-phenyl-1,3,8-triaza-Spiro[4.5]Decan-4-one;
3488-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-triaza-Spiro[4.5]decane-2,4-dione;
349tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamate acids;
350N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylacetamide;
351N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylmethanesulfonamide;
352[(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamoyl]methyl ester of acetic acid;
353N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-ndimethylacetamide;
354(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbonyl)methyl ester acetic acid;
3552-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)-3-(1H-imidazol-2-yl)propionic acid;
3562-4-{2-[4-(3-nitropyridine-2-yl)-[1,4]diazepan-1-yl]ethyl}phenoxy)benzothiazole;
3572-(4-piperidine-1-ylmethylene)benzothiazole;
3581-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol;
3591-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol;
360{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol;
361N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanesulfonamide;
362N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetate;
363methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
364{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea;
365N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-triptorelin;
366{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
3672-[4-(4-methanesulfonamide the Jn-1-ylmethyl)phenoxy]benzothiazole;
3681-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline;
3692-(4-(morpholine-4-ylmethylene)benzothiazole;
370phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
371N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide;
372ethyl ester of 3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
3733-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
374ethyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
376ethyl ester of 1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
3771'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
378{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}the CEC shall propylethylene;
379triftoratsetata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acids;
3802-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethanol;
3812-[2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethoxy]ethanol;
3823-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propan-1-ol;
383{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl(3-tetrazol-1-ylpropyl)amine;
384{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl(3-pyrrol-1-ylpropyl)amine;
3854-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile
386(2-cyanoethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
387{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(2H-tetrazol-5-yl)propyl]amine;
388
389{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl[3-(2H-tetrazol-5-yl)propyl]amine;
390(2-hydroxy-1,1-dimethylethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
391{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(1H-[1,2,4]triazole-5-yl)propyl]amine;
392{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-methyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
393{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-phenyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
3942-(4-{2-[4-(1-methyl-1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
3952-(4-{2-[4-(2-methyl-2H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
3961-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile;
3972-(4-{2-[4-(1H-[1,2,3]triazole-4-yl]ethyl}Fenox is)benzothiazole;
398ethyl ester of 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}butyric acid;
399ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
4002-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione;
4014-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
4021-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-he;
403N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylmethyl-1,3-diamine;
404methyl ester 5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentanol acids;
405N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
406[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide morpholine-4-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methansulfonate;
4085-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentane acid;
4091-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}isopropylamino)propyl]pyrrolidin-2-he;
4101-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
4111-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
4121-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}propylamino)propyl]pyrrolidin-2-he;
413ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
414ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
4154-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methanesulfonamide)butyric acid;
416 ({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)acetic acid;
417ethyl ester of 6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
418ethyl ester of 7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
4196-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
4207-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
421N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine;
422N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
423N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isobutyramide;
424N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]benzamide;
425N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-4-chlorine is benzamid;
426N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide;
427triftoratsetata salt [3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide propane-2-sulfonic acid;
428ethyl ester 8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
4291-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-3-phenylacetone;
4308-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
431[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide tetrahydrofuran-2-carboxylic acid;
432N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-2-hydroxyacetate;
4334-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
4341-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}is irreligion-2-he;
4351-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-he;
4361-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-he;
4371-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-he;
438[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine;
439N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine;
440N-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)isobutyramide;
4411-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-2-isopropylamino;
4421-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-isopropylamino;
443methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acids;
444N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide;
445{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid;
4461-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-he;
4471-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-he;
448{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea;
449N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}Arslanova acid;
450N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetate;
451N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-triptorelin;
4522-[4-(1,1-dioxo-1/6-thiomorpholine-4-ylmethyl)phenoxy]benzothiazole;
453tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl}carbamino acids;
454N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide;
455N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfone;
4561-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-atilmotin;
4571-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene;
458{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid;
459{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid;
460N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide;
461N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide;
462ethyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
463N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide;
464N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
4651-{1-4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-proprotein;
466propyl ester N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
4671-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metalmachine;
4691-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloctane;
4701-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metalmachine;
471N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide;
472methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acids;
473methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acids;
474N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylocella acid;
475N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine;
476Isopropyl ether {1-[4-(benzothiazol-yloxy)benzyl]piperidine-4-yl}carbamino acid;
4773-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloctane;
478{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ether acetic acid;
479{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea;
4822-[4-(2-morpholine-4-ylethoxy)phenoxy]benzothiazole and
4832-[4-(2-piperidine-1-ylethoxy)phenoxy]benzothiazole.

Connection of additional variants of the present invention, where X represents NR5where R5represents one of N and CH3obtained by the synthesis methods presented in schemes a-C, F, G and J-L, have L4-inhibitory activity and is selected from the group consisting of the following compounds:

ExampleConnection
371-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
38{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclepro iletildigini;
39Cyclohexylethyl{2-[4-(1-methyl-1H-benzoimidazol-2-yloxy)phenyl]ethyl}amine;
1171-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1181-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1191-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
123{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
1242-[4-(2-pyrrolidin-1-retil)phenoxy]-1H-benzoimidazol;
1252-[4-(2-azepin-1-retil)phenoxy]-1H-benzoimidazol;
126{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}dibutylamine;
1271-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
128methyl ester 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
129{2-[4-(1H-benzo is midazol-2-yloxy)phenoxy]ethyl}cyclohexylamine;
1302-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
1312-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
1322-[2-(4-piperidine-1-ylethoxy)phenoxy]-1H-benzoimidazol;
133(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
1341-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
1382-[4-(2-azepin-1 ylethoxy)phenoxy]-1H-benzoimidazole;
139{3-[4-(1H-benzoimidazol-2-yloxy)phenoxy]propyl]dimethylamine;
1402-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]-1H-benzoimidazol;
141{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl]dimethylamine;
1422-[4-(2-morpholine-4-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2302-[4-(2-piperidine-1-retil)phenoxy]-1H-benzoimidazol;
21 1-(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
480(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol and
485ethyl ester of 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid.

Compounds of the present invention can be obtained in accordance with the reaction schemes described below. These schemes are based on two direct methods of synthesis of the target compounds, where the synthesis starting from the end of the synthesized molecules. The person skilled in the art it will be obvious that the synthesis of some compounds are more preferable to be in accordance with any one of the presented schemes.

For various of the described compounds can be used starting compound, which, ultimately, has the necessary deputies, although, if necessary, the reaction scheme can be carried out using protection or not. Starting compound can be obtained from commercial sources or they can be synthesized by methods known to experts in this field. Alternatively, it may be necessary, instead of the final desired Deputy, to use the right group, which may be present in this reaction scheme, and which can then be replaced by the appropriate Deputy. Any product containing a chiral center can be separated into its enantiomers by standard methods.

Options illustrated in this description of the methods include, if it is chemically appropriate, one or several stages, such as hydrolysis, halogenoalkane, the introduction of protective groups and removing the protective group. These stages can be carried out in the light presented in this description of the methods and methods that are well known to the average expert in the field.

During one of the methods for producing compounds of the present invention, it may be necessary and/or desirable to protect sensitive or reactive group on any of the examined molecules. In addition, the compounds of the present invention can be modified with the use of protective groups, and such compounds, its precursors or prodrugs also included in the scope of the present invention. This can be achieved using standard protective groups, such as described in “Protective Groups in Organic Chemistry”, ed. J.F.W. McOmie, Plenum Press, 1973 and T.W. Greene &P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rded., John Wiley & Sons, 1999. These protective groups can be removed at the appropriate later stage met the DAMI, known in this field.

Scheme And

In scheme A, where n is 1 or 2, commercially available 4-benzyloxyphenol A1, alkylate aminoalkylindole A2; some aminoalkylated are commercially available. These reactions can be carried out with a wide range of temperatures, including room temperature and higher temperatures, in the presence of inorganic bases, which, as you know, facilitates O-alkylation, such as, but not limited To2CO3Cs2CO3and their mixtures (J. Med. Chem., 1997, 40, 1407-1416). Suitable solvents include, but are not limited to, DMF. Removing the benzyl group of compound A3 can be carried out under conditions of catalytic hydrogenation, well known in this area (T.W. Greene &P.G.M. Wuts, Protective Groups in Organic Synthesis, 3ded., John Wiley & Sons: New York, 1999). Suitable catalysts include, but are not limited to, Pd coal (Pd/C) in solvents such as ethyl acetate, alcohols, and mixtures thereof. Examples of alcohols include, but are not limited to, CH3HE, ethanol, i-LON. Such reactions are usually carried out at room temperature. In some embodiments of the invention, the removal of the benzyl group of compound A3 can be done by restoring the metal in solution or Hydra is the formation under conditions of phase transfer at the appropriate temperatures. For example, the reduction reaction of the metal in the solution is usually carried out at temperatures below room temperature (-33°C). The reaction of the compound A4 with aromatic bicyclic system A5, which, if necessary, is properly protected, can be carried out in a wide temperature range, including room temperature and higher temperatures, in the presence of a suitable base, including but not limited to, amine or inorganic base, as defined above. Suitable amine bases include, but are not limited to, triethylamine (tea), N,N-diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), associated with resin amine bases and mixtures thereof. If X represents oxygen or sulphur, the protective group is not administered. Suitable solvents include, but are not limited to, DMF, CH3CN, acetone and mixtures thereof. If X represents NR5where R5is a suitable silicon-containing protective group such as SEM (trimethylsilylethynyl), deleting the specified silicon-containing protective groups in NR5can be carried out under conditions well known in the art (see Greene et al., specified above). Typical reaction conditions include, but are not limited to, the use of tetrabutylammonium fluoride (TBAF) in under Odesa solvents, such as THF, at elevated temperatures.

Scheme

In the diagram, commercially available 4-benzyloxyphenol A1, alkylate dihalogenoalkane, preferably, dibromethane, such as 1,2-dibromoethane and 1,3-dibromopropane, B1, both of which are commercially available in a wide range of temperatures, however, are preferred elevated temperature (Zhou, Z.-L. et al., J. Med. Chem., 1999, 42, 2993-3000). Such reaction is carried out in the presence of inorganic bases, which, as you know, facilitates O-alkylation, such as, but not limited To2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, CH3JV and DMF. Connection structure B2 is treated with amines B3 in the absence or in the presence of a suitable amine base as described above, in a wide range of temperatures, however, are preferred elevated temperature. Suitable solvents include CH3SP, CH2Cl2and DMF. Subsequent conversion of the obtained structure products A3 in the connection structure A6 were carried out as described above for scheme A.

Scheme

In the diagram With the benzyl group of compounds of structure B2 can be removed under conditions catalyti the definition of hydrogenation, well known in the art (Greene et al., see above). Suitable catalysts include, but are not limited to, Pd/C in solvents such as THF and a mixture of THF/ethanol. Such reactions are usually carried out at room temperature. Removing the benzyl group of compound B2 can be carried out by hydrogenation under conditions of phase transfer using suitable solvents and at suitable temperatures. Compounds of General structure C1 is treated with amines of structure B3, in the absence or in the presence of a suitable amine base as described above, in a wide range of temperatures, however, are preferred elevated temperature. Suitable solvents include CH3SP, CH2Cl2and DMF. Subsequent conversion of the obtained structure products A4 in connection A6 were carried out as described above for scheme A.

Scheme D

In scheme D, compounds of structure A6 can also be obtained by treatment of compounds of structure S1 aromatic bicyclic compounds A5, where X=S and, in the presence of a suitable inorganic bases defined above, and in a wide range of temperatures, however, are preferred elevated temperature. Suitable solvents include, but are not limited to, DMF, the H 3JV and mixtures thereof. The conversion of compounds of structure D1 connection structure A6 can be carried out by treating compounds of structure B3. Such reactions can be carried out in the absence or in the presence of a suitable amine base, as defined above, or inorganic bases, such as, but not limited To2CO3Cs2CO3and mixtures thereof, as described above, in a wide range of temperatures, however, are preferred elevated temperature. Suitable solvents include, but are not limited to, CH3JV and DMF.

This is provided that when X represents NR5where R5is a suitable silicon-containing protective group, in this case, the synthesis is carried out in accordance with the methodology described above. Removing silicon-containing protective group at the end of the synthetic sequence can then be carried out under the conditions described in the literature (Greene et al., see above).

Scheme E

In scheme E, compounds of structure E1 is treated with an aromatic bicyclic compounds A5, where X=S (and also why not?), in the presence of a suitable inorganic bases defined above, in a wide temperature range, however, preferred Vlada elevated temperatures. Suitable solvents include, but are not limited to, DMF, CH3JV and mixtures thereof. Connection structure of E2 can be converted into compounds of structure E3 in normal conditions, synthesized, including but not limited to, the use of RVG3at elevated temperatures. Suitable solvent includes, but not limited to, benzene. Connection structure of E2 can be converted into compounds of structure E4 in standard conditions of sulfonation, well known in this field. Such conditions include, but are not limited to, the use of TsCl to obtain tozilaty, as shown in the diagram, in the presence of an amine base and CH2Cl2at room temperature. The conversion of compounds of structure E3 in connection patterns E5 can also be carried out by treating compounds of structure B3. Such reactions may be carried out in the absence or in the presence of a suitable amine base, described above, or inorganic bases, such as, but not limited To2CO3Cs2CO3and mixtures thereof, in a wide range of temperatures, however, are preferred elevated temperature. Suitable solvents include, but are not limited to, CH3JV and DMF. Connection patterns E4 can be converted to soybeans is inane patterns E5 by treatment with compounds of structure B3. Such reactions may be carried out in the absence or in the presence of a suitable amine base as described above, in a wide temperature range. Suitable solvents include, but are not limited to, CH3JV and DMF.

This is provided that when X represents NR5where R5is a suitable silicon-containing protective group, in this case, the synthesis is carried out in accordance with the methodology described above. Removing silicon-containing protective group in the final stage of the synthesis can then be carried out under the conditions described in the literature (Greene et al., see above).

Scheme F

In scheme F commercially available 4-(2-hydroxyethyl)phenol and 4-(2-hydroxypropyl)phenol is converted into the corresponding alkylhalogenide F1, where L represents chloride or bromide, in standard conditions, synthesized or chlorination. Such conditions include, but are not limited to, processing 48% solution Nug at elevated temperatures. Then the obtained Bromphenol patterns F1 treated with amines of structure B3, in the absence or in the presence of a suitable amine base as described above, in a wide temperature range. Suitable solvents include, but are not limited to, CH3JV and DMF. The reaction of the compound F2 with aromatic the Russian bicyclic system A5, which, if necessary, is properly protected, can be carried out in a wide temperature range, including room temperature and higher temperatures, in the presence of a suitable amine or inorganic base, as defined above. Suitable solvents include, but are not limited to, DMF, CH3JV, acetone and mixtures thereof. If X represents O or S, then the protective group is not administered. If X represents NR5where R5is a suitable silicon-containing protective group such as SEM (trimethylsilylethynyl), deleting the specified silicon-containing protective groups in NR5can be carried out under conditions well known in the art (see Greene et al., specified above). Typical reaction conditions include, but are not limited to, the use of TBAF in suitable solvents, such as THF, at elevated temperatures.

Scheme G

In scheme G connection G1, where n is 1 or 2, and L is a bromide or chloride, is a commercially available compound, or it can be obtained from compounds marked with **, and connection G1, where n is 1, can be obtained from 4-(2-hydroxyethyl)phenol and benzylbromide standard alkylation conditions. Benzyl GRU is PA in G1 serves as a protective group. In this sequence of reactions may be used and other compatible protective group known in this field. Compounds of General structure G2 can be obtained by treating the amines of the General structure B3, in the absence or in the presence of a suitable amine base as described above, in a wide temperature range. Suitable solvents include, but are not limited to, CH3JV and DMF. Removal of the benzyl may be carried out under conditions of catalytic hydrogenation, is well known in the art (Greene et al., see above). Suitable catalysts include, but are not limited to, Pd/C in solvents such as ethyl acetate, alcohols, and mixtures thereof. Examples of alcohols include, but are not limited to, CH3HE, ethanol, i-LON. Such reactions are usually carried out at room temperature. In some embodiments of the invention, the removal of the benzyl group of compound G2 can be carried out by hydrogenation under conditions of phase transfer at the appropriate temperatures. Subsequent conversion of the obtained products F2 in the final target compound F3 were carried out as described above for scheme F.

Scheme N

In the diagram N commercially available 4-benzyloxyphenol A1, is treated with epichlorohydrin N1, both of which are commercially available is I. This reaction can be carried out in a wide temperature range, in this case, it is preferable to elevated temperature and in the presence of inorganic bases, such as, but not limited To2CO3Cs2CO3and mixtures thereof. Suitable solvent includes, but not limited to, DMF. The conversion of compounds of structure H2 in the connection structure of H3 can be carried out by treating the amines of the General structure B3, in the absence or in the presence of a suitable amine base, described above, or inorganic bases, such as, but not limited To2CO3Cs2CO3and mixtures thereof, in a wide temperature range, in this case, it is preferable fever. Suitable solvents include, but are not limited to, CH3JV and DMF. Removal of benzyl groups on H3 can be carried out under conditions of catalytic hydrogenation, is well known in the art (Greene et al., see above). Suitable catalysts include, but are not limited to, Pd/C in solvents such as ethyl acetate, alcohols, and mixtures thereof. Examples of alcohols include, but are not limited to, ethanol, CH3HE and i-LON. Such reactions are usually carried out at room temperature. In some embodiments of the invention, the removal of the benzyl group on the 2 may be effected by hydrogenation under conditions of phase transfer using suitable solvents and at suitable temperatures. The conversion of compounds of structure H4 in the final target compound H5 can be carried out by treating the aromatic bicyclic system A5, where X represents Oh, in the presence of a suitable inorganic bases defined above, in a wide temperature range, in this case, it is preferable to lower the temperature. Suitable solvent includes, but not limited to, acetone.

This is provided that when X represents NR5where R5is a suitable silicon-containing protective group, in this case, the synthesis is carried out in accordance with the methodology described above. Removing silicon-containing protective group at the final stage of the synthesis can then be carried out under the conditions described in the literature (Greene et al., see above).

Scheme I

In scheme I, compounds of type I5 is obtained by heating the commercially available 4-hydroxyphenylarsonic acid with 2-aminothiophenol, if X represents S. if X represents Oh, use 2-aminophenol. Two parent compound is heated in the absence of solvent, and the resulting phenols I3 process dihalogenoalkane, preferably, dibromethane, such as 1,2-dibromoethane and 1,3-dibromopropane, B1, both of which became the tsya commercially available, in a wide temperature range, in this case, it is preferable fever (Zhou, Z.-L. et al., see above). Such reaction is carried out in the presence of inorganic bases, which, as you know, facilitates O-alkylation, such as, but not limited To2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, CH3JV and DMF. Connection structure I4 is treated with amines B3, in the absence or in the presence of a suitable amine base as described above, in a wide range of temperatures, however, are preferred elevated temperature. Suitable solvents include CH3SP, CH2Cl2and DMF.

Scheme J

The diagram J connection patterns J1 can be further improved within the stated ambitions of obtaining the target compounds with a large number of functional groups. For example, this can be done hydrolysis methods, well known in this field, such as, but not limited to, methods using aqueous solutions Li, CON or Paon, or aqueous solutions of HCl or CH3CO2N, or methods using (CH3)3Si. In addition, the person skilled in the art it will be obvious that nectariniidae is more preferable to obtain any one of the available methods, and that in the initial stage can be obtained salt of the desired compounds. Compounds of structure J2 can then be modified to obtain amides well-known methods, including but not limited to, a method using (L2)2for conversion into the intermediate acid chloride followed by treatment of amines of structure B3. Alternatively, it may be treated by standard reaction with the formation of amide bonds, including but not limited to, reaction with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (DCI), without adding or adding NOWT, and amines of structure B3. Connection patterns J4 can then be modified by reductive amination under standard conditions well known in this field, including, but not limited to, the use of amine structure B3 and N(SLA)3in an appropriate solvent such as CH2Cl2in an appropriate solvent such as CH2Cl2, Cl2Cl2Cl or CF3CH2HE.

The schema For

In the diagram To the commercially available 3-fluoro-4-hydroxybenzoic acid C, is converted into amides K2, under standard reaction conditions, the combination of peptides, well known in this field, using the amines of structure B3, such as, but is s limited to, hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (DCI), 1,3-dicyclohexylcarbodiimide (D), hexaflurophosphate O-(7-asobancaria-1-yl)-N,N,N',N'-tetramethylurea (NATI), hexaflurophosphate O-benzotriazol-1-N,N,N',N'-tetramethylurea (U) and mixtures thereof. Suitable solvents include, but are not limited to, CH2Cl2and THF. Received amides patterns K2 reduced to amines of the formula K3 in terms of recovery, well known in this field, including, but not limited to, the use of lithium aluminum hydride in a suitable solvent, such as, but not limited to them, THF. Convert benzylamino K3 in the final target compound K4 can be carried out by treating the aromatic bicyclic system A5, where X represents S or O, in the presence of a suitable inorganic bases and a wide range of temperatures, however, are preferred elevated temperature. Suitable inorganic bases include, but are not limited to, K2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, acetone and CH3SP.

This is provided that when X represents NR5where R5is a suitable silicon-containing protective group, in this case, the synthesis is carried out is in accordance with the methodology described above. Removing silicon-containing protective group at the final stage of the synthesis can then be carried out under the conditions described in the literature (Greene et al., see above).

Scheme L

In scheme L illustrates an alternative option for obtaining compounds of formula (I), where n is 0. The original connection L1, 4-hydroxybenzaldehyde, is converted into ethers of the formula L2 by treating aromatic bicyclic system A5, where X represents S or O, in the presence of a suitable inorganic base in a wide temperature range, in this case, it is preferable fever. Suitable inorganic bases include, but are not limited to, K2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, acetone and CH3The JV. This is provided that when X represents NR5where R5is a suitable silicon-containing protective group, in this case, the synthesis is carried out in accordance with the methodology described above. Removing silicon-containing protective group in the final stage of the synthesis can then be carried out under the conditions described in the literature (Greene et al., see above). The aldehydes of the formula L2 is converted into amines of the formula L3 in conditions will restore inogo amination using an amine of formula B3. Suitable reducing agents include PA(SLA)3NR and NN3used without addition or with the addition of activating agents, such as acetic acid or ZnCl2. Suitable solvents include THF and methanol, and the reaction temperature may be from 0°C to 70°C. the Preferred reaction conditions include the presence of PA(SLA)3BH in THF at room temperature.

The expression “pharmaceutically acceptable salts, their esters and amides of the compounds of the present invention” means salts, amides and esters of the compounds of the present invention, which is understandable chemist-pharmacist, that is, it means compounds that are non-toxic and attach the specified compounds of the present invention is favorable pharmacokinetic properties. The expression “compounds with favorable pharmacological properties” clear chemist-pharmacist and means compounds that are non-toxic and possess pharmacokinetic properties as acceptable taste, good absorbiruyaci, the desired tissue distribution and the desired parameters of metabolism and excretion. Other factors that are more important from a practical point of view, and which should be considered when choosing these compounds are the value of the outcome is s substances, the ease of crystallization, yield, stability, hygroscopicity, and the fluidity of the medicine mass.

In addition, an acceptable salts of carboxylates include sodium, potassium, calcium and magnesium salts. Examples of suitable cationic salts include salts of Hydrobromic, idiscovered, hydrochloric, perarnau, sulfuric, maleic, fumaric, malic, tartaric, citric, benzoic, almond, methansulfonate, gidrodesulfirovanii, benzosulfimide, oxalic, palmitic, 2-naphthalenesulfonates, p-toluensulfonate, cyclohexylsulfamate and sugar acids.

Presented below is a more complete list of acids and bases that can be used to obtain pharmaceutically acceptable salts, include the acid, such as acetic acid, 2,2-dichlorsilane acid, an acetylated amino acid, adipic acid, alginic acid, ascorbic acid, L-aspartic acid, benzolsulfonat acid, benzoic acid, 4-acetamidobenzoic acid, (+)-camphoric acid, camphorsulfonic acid, (+)-(1S)-camphor-10-sulfonic acid, capric acid, Caproic acid, Caprylic acid, cinnamic acid, citric acid, ciclamino acid, modellerna acid, ethane-1,2-disulfonate acid, econsultancy acid, 2-hydroxide the sulfonic acid, formic acid, fumaric acid, galacturonic acid, gentisic acid, glucoheptonate acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, α-oxoglutarate acid, glycolic acid, hippuric acid, Hydrobromic acid, hydrochloric acid, (+)-L-lactic acid, (±)-DL-lactic acid, lactobionic acid, maleic acid, (-)-L-malic acid, malonic acid, (±)-DL-mandelic acid, methanesulfonate acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonate acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, orotic acid, oxalic acid, palmitic acid, pamula acid, phosphoric acid, L-pyroglutamyl acid, salicylic acid, 4-aminosalicylic acid, sabotinova acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-tartaric acid, titanova acid, p-toluensulfonate acid and undecylenoyl acid; and bases, such as ammonia, L-arginine, benethamine, benzathine, calcium hydroxide, choline, deanol, diethanolamine, diethylamine, 2-(diethylamino)ethanol, ethanolamine, Ethylenediamine, N-methylglucamine, geranamine, 1H-imidazole, L-lysine, magnesium hydroxide, 4-(2-hydroxyethyl)morpholine, piperazine, potassium hydroxide, 1-(2-hydroxyethyl)the feast of Aidin, secondary amines, sodium hydroxide, triethanolamine, tromethamine and zinc hydroxide. See, for example, S.M. Berge et al. “Pharmaceutical Salts”, J. Pharm. Sci. 1977, 66:1-19, introduced in the present description by reference.

Suitable examples of esters include esters in which one or more carboxyl substituents replaced by p-methoxybenzenediazonium,

2,4,6-trimethylbenzenesulfonyl, 9-antioxidation,

CH3SCH2COO-, tetrahydrofur-2-rockstarvania,

tetrahydropyran-2-rockstarvania, FSD-2-rockstarvania,

benzoylmethylecgonine, p-nitrobenzenediazonium,

4-pyridylcarbonyl, 2,2,2-trichlorocarbanilide,

2,2,2-tribromoethanol, tert-butyloxycarbonyl,

tert-meloxicalm, diphenyltetrazolium,

triphenylcarbenium, adamantanecarbonyl,

2-benzyloxycarbonyl, 4-methyltrioctylammonium

or tetrahydropyran-2-rockstarvania.

Compounds of the present invention can be used in pharmaceutical compositions to treat patients (humans and other mammals suffering from disorders mediated by the action of the enzyme L4. In particular, the compounds of the present invention can be used in pharmaceutical compositions intended for the treatment of inflammation, More specifically, compounds of the present invention can be used in pharmaceutical compositions intended for the treatment of such inflammatory conditions as inflammatory bowel disease (IBD) (for example, Crohn's disease and ulcerative colitis), chronic obstructive pulmonary disease (COPD), arthritis, psoriasis, asthma, cystic fibrosis, atherosclerosis, rheumatoid arthritis and multiple sclerosis.

The present invention relates to pharmaceutical compositions containing these compounds, and to methods of using such compositions for the treatment or prevention of conditions mediated by the action of the enzyme L4. Accordingly, the present invention also relates to pharmaceutical compositions containing at least one compound of the present invention, preferably dispersed in a pharmaceutically acceptable carrier. In accordance with the present invention, such a composition is at least one compound in a quantity sufficient to inhibit the enzymatic activity L4. More specifically, in accordance with the present invention, such a composition is at least one compound in a quantity sufficient to achieve the anti-inflammatory effect.

Accordingly, the present invention also addresses the pharmaceutical is a mini-composition, comprising at least one compound of the present invention in a pharmaceutically acceptable carrier, where the specified connection is present in an amount to provide an anti-inflammatory effect. This composition comprises a unit dosage form containing at least one compound of the present invention. In a preferred embodiment of the invention the specified at least one compound of the present invention contained in the specified pharmaceutical composition capable of inhibiting the enzymatic activity L4 in the quantity in which this compound is present in a given pharmaceutical composition, if such a pharmaceutical composition is introduced to a given patient or subject in the form of a single dosage form.

Used the term “unit dosage form” and its grammatically equivalent means physically discrete form suitable for administration to humans and other animals as a unified doses, where each dose contains a predetermined pharmacologically effective amount of the active ingredient, is designed so that it produces the desired pharmacological effect. The specific composition of the new unit dosage forms of the present invention is determined by the properties of the active is the first ingredient and directly depends on these properties and limitations of existing methods of mixing, such as the active ingredients intended for therapeutic treatment of humans and other animals.

The pharmaceutical compositions can be obtained using standard pharmaceutical excipients and standard methods of preparation of medicines. Examples of suitable unit dosage forms are tablets, capsules, coated tablets, Packed in packages of powders, granules, wafers and the like, the packaging of many separate unit dosage forms for repeated administration, as well as liquid solutions or suspensions. Oral dosage forms can be elixirs, syrups, capsules, tablets, etc. are Examples of solid carriers include substances which are usually used for the preparation of pills or tablets, such as lactose, starch, glucose, methylcellulose, magnesium stearate, dicalcium phosphate, mannitol and the like; thickeners, such as tragacanth gum and methylcellulose US, fine-grained SiO2, polyvinylpyrrolidone, magnesium stearate, etc. Standard liquid excipients for oral preparations are ethanol, glycerol, water, etc. All excipients, if necessary, can be mixed with inert diluents (e.g., carbonates of sodium and calcium, phosphates of sodium and calcium and lactose), dezinfeciruyuhimi agents (e.g. cornstarch and algina the second acid), diluents, granulating agents, lubricants (e.g. magnesium stearate, stearic acid and talc), binding agents (e.g. starch and gelatin), thickeners (for example, paraffin wax and vaseline oil), flavors, dyes, preservatives, etc. in accordance with the standard methods of preparing dosage forms known in the field. May be present in the coating, and such coatings include, for example, glycerylmonostearate and/or glycerylmonostearate. Capsules for oral administration include hard gelatin capsules in which the active ingredient is mixed with a solid diluent, and soft gelatin capsules in which the active ingredient is mixed with water and oil, such as peanut oil, liquid petroleum jelly or olive oil.

Parenteral dosage forms can be prepared using water or other sterile media. For intramuscular, intraperitoneal, subcutaneous and intravenous administration of the compounds of the present invention is usually prepared in the form of sterile aqueous solutions or suspensions, buffered to achieve the appropriate pH and isotonicity. Suitable aqueous media are ringer's solution and isotonic sodium chloride. Aqueous suspensions may include suspendresume Genty, such as cellulose derivatives, sodium alginate, polyvinylpyrrolidone and tragacanth gum, and a wetting agent such as lecithin. Suitable preservatives for aqueous suspensions are ethyl and n - propyl-p-hydroxybenzoate.

Physiologically acceptable carriers well known in this field. Examples of liquid carriers are solutions in which the compounds of the present invention to form solutions, emulsions and dispersions. Solid and liquid compositions can be compatible antioxidants, such as methylparaben and propylparaben, and such antioxidants can serve as sweeteners.

The pharmaceutical compositions of the present invention may include suitable emulsifiers customarily used in emulsion compositions. Such emulsifiers are described in known publications, such as H.P. Fiedler, 1989, Lexikon der Hilfsstoffe fur Pharmazie, Kosmetic und agrenzende Gebiete, Cantor ed., Aulendorf, Germany, and the guides Handbook of Pharmaceutical Excipients, 1986, American Pharmaceutical Association, Washington, DC; and the Pharmaceutical Society of Great Britain, London, UK, which are introduced in the present description by reference. In the composition of the present invention can also be added gelling agents. Examples of gelling agents are derivatives of polyacrylic acid, such as carbomer, and more specifically, carbopol different types which usually Pris testout in the amount of from about 0.2% to 2%. A suspension can be obtained in the form of creams, ointments, including ointment, containing no water; the emulsion of the type water-in-oil”emulsion of the type oil-in-water, emulsion, gel or gel.

It is envisaged that the compounds of the present invention can be administered orally or parenterally, namely, intravenously, intramuscularly, intraperitoneally, subcutaneously, rectally and topically, or by inhalation. For oral administration, the compounds of the present invention is usually prepared in the form of tablets, capsules, solutions or suspensions.

The terms “therapeutically effective amount” or “effective amount” and grammatically equivalent means the amount of active compound or pharmaceutical agent that produces biological or clinical response of the animal or person covered by the researcher, veterinarian, physician or other Clinician, where the response includes the weakening of the symptoms of the disease or disorder being treated. The terms “patient” or “subject” includes mammals, such as humans and animals (e.g. dogs, cats, horses, rats, rabbits, mice, and primates, non-human, in need of supervision, conducting experiments, treatment or prevention of the relevant disease or status who I am. Preferably, the patient is the man.

Effective doses of the compounds of the present invention can be determined by standard methods. The specific dose level required for each specific patient depends on a number of factors, including the severity of the condition, the route of administration and body weight of the patient.

Usually it is envisaged that the daily dose of compound (regardless of whether it is introduced as a single dose or fractional doses) is in the range from about 0.01 mg to 1000 mg per day, preferably from about 1 mg to 500 mg per day, and most preferably, from about 10 mg to 200 mg per day. If the dose is expressed in units on body weight, this dose will be approximately from 0.0001 mg/kg to 15 mg/kg, preferably from about 0.01 mg/kg to 7 mg/kg, and most preferably, from about 0.15 mg/kg to 2.5 mg/kg

The estimated oral dose is from about 0.01 mg/kg to 500 mg/kg, more preferably, from about 0.05 mg/kg to 100 mg/kg, and entered as 1-4 divided doses. Some compounds of the present invention can be administered orally in doses of from about 0.05 mg/kg to 50 mg/kg / day, although other compounds can be introduced in doses of 0.05 mg/kg to about 20 mg/kg / day. Dose for infusion may be in the range of about 1.0 to 1.0×104mcg/kg/min) inhibitor mixed with FA is matemticas acceptable carrier, at the time of infusion from several minutes to several days. For the local introduction of the compounds of the present invention can be mixed with a pharmaceutically acceptable carrier at a concentration of pharmaceuticals from about 0.1 to about 10% in relation to the media.

In the present description is also considered a method of treating inflammation in patients suffering from or susceptible to inflammatory conditions. Also considered a method of treating L4-mediated condition. These methods include the introduction to the patient an effective amount of a pharmaceutical composition comprising a unit dose of the active ingredient, which is at least one of the compounds of the present invention, dispersed in a pharmaceutically acceptable carrier.

For brevity, in the present description, some quantitative values are given without the word “about”. However, it is clear that each given quantity, regardless of whether it is accompanied by the word “about” or not, means the actual value, and indicates the approximate value for this value, which can be determined by the person skilled in the art, including the approximate value obtained in the experimental conditions and/or measurement of this value. If the output is in percent, this output indicates the mass of the obtained substance are compared with the maximum number of the same substance, which can be obtained in specific stoichiometric conditions. The concentration, expressed in percent, mean mass relations, unless otherwise stated.

EXAMPLES

Below are examples illustrating the present invention. These examples should not be construed as limiting the present invention. They illustrate only one of the possible methods of carrying out the invention. The person skilled in the art will be able to find other methods of implementing the present invention, which, in his opinion, seem to him appropriate. However, it is clear that these methods are also included in the scope of the present invention.

General experimental procedures

NMR spectra were obtained on a spectrometer Bruker model D400 (400 MHz) or D500 (500 MHz). Below data1H-NMR in the following format: chemical shift in ppm is in the lower field relative to the signal tetramethylsilane as a reference (multipletness, the interaction constant J in Hz, integration).

Mass spectra were obtained on equipment Agilent series 1100 MSD through ionization elektrorazpredelenie (ESI)in positive or negative fashion. The term “calculated weight” is La molecular formula means a lot of monoisotope connection.

When HPLC with reversed-phase retention time is expressed in minutes, determined using the methods and conditions described below:

Equipment: Gilson 215

Solvent: CH3CN (0.05% of triperoxonane acid, TFA)/H2O (0.05% of TFA)

Flow rate: 25 ml/min

Gradient: 0 min 10% SN3CN; 20 minutes, linear gradient to 99% of CH3CN;

Column: YMC-Pack ODS-A AA 12505-1530WT SH-362-5 (S-5 μm, 12 nm, 150×30 mm)

Temperature: 25°C

Wavelength: dual detection at 220 and 254 nm.

Column flash chromatography was performed using a systems ISCO Foxy 200 or ISCO OPTIX 10X on one of the following commercially available pre-Packed columns: Biotage 40S (SIO, SIS2, 40 g), Biotage 40M (SIO, SIS2, 90 g), Biotage 40L (SIO, SIS2, 120 g), Biotage 65M (SIO, SIS2300 g) or ISCO Redisep (SIO, SIS2, 10 g, 12 g, 35 g, 40 g or 120 g).

Example 1

2-(4-benzyloxyphenyl)ethylbromide

To a stirred solution of 4-benzyloxyphenol (72 g, 359,6 mmol) in CH3SP (600 ml) was added dibromoethane (155 ml of 1.80 mol) and K2CO3(105 g, 759,9 mmol). The brown suspension was heated under reflux and left to mix for 96 hours. The resulting suspension was cooled to room temperature, diluted with acetone (250 ml) and filtered through diatomaceous earth, and then washed with additional acetone is. The filtrate was concentrated under reduced pressure. The resulting oil was dissolved in CH3HE (500 ml) and the solution was stirred for 2 hours. After filtration and drying air received 70 g specified in the connection header (228 mmol, yield 63%) as a solid brownish-yellow color.1H NMR (400 MHz, CDCl3): 7,60-7,30 (m, 5H), to 6.88 (d,J=8,4, 2H), 6,80 (l,J=8,4, 2H), 4,70 (s, 2H), 3,79 (t,J=5,8, 2H), of 3.07 (t,J=5,8, 2H).

Example 2

1-[3-(4-benzyloxyphenyl)propyl]bromide

To a stirred solution of 4-benzyloxyphenol (25 g, was 124.9 mmol) in CH3JV (125 ml) was added dibromopropan (63 ml, 624 mmol) and K2CO3(34,5 g, 250 mmol). The brown suspension was heated under reflux and left to mix for 66 hours. Then the suspension was cooled to room temperature and twice filtered through layers of diatomaceous earth. Layers were washed CH3CN and the combined filtrates were concentrated under reduced pressure. The resulting oil was purified on SIO, SIS2(300 g; 33% of CH2Cl2/hexane) to give 35.4 g (110 mmol, yield 88%) solid brown color.1H NMR (400 MHz, CDCl3): 7,46-7,29 (m, 5H), 6,85 (kV,J=8,1, 2H), 6,82 (kV,J=7,2, 2H), to 5.03 (s, 2H), 4,06 (t,J=5,8, 2H), 3,61 (t,J=6,5, 2H), 2,39 (m,J=6,2, 2H).

Example 3

4-(2-what amatucci)phenol

2-(4-benzyloxyphenyl)ethylbromide (example 1; 70 g, 227 mmol) was dissolved in THF (500 ml). To the solution was added Pd on coal (10 wt.%, 7 g) in suspension in ethanol (50 ml). The resulting suspension was placed in hydrogenator Parra under pressure 40 psi H2and was stirred overnight. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate was concentrated under reduced pressure to get to 48.5 g (224 mmol, yield 99%) solids brownish-yellow color.1H NMR (400 MHz, CDCl3): 6,83 (l,J=9,1, 2H), 6,77 (l,J=9,1, 2H), 4,51 (s, 1H), 4,24 (t,J=6,3, 2H), 3,62 (t,J=6,3, 2H).

Example 4

4-(3-bromopropane)phenol

[3-(4-benzyloxyphenyl)propyl]bromide (10 g, and 31.1 mmol) was dissolved in THF (100 ml). To the solution was added 10% palladium on coal (1 g) in suspension in THF (20 ml). The resulting suspension was placed in hydrogenator Parra under pressure 40 psi H2and was stirred overnight. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 7 g (30,5 mmol, yield 98%) solids brownish-yellow color.1H NMR: (400 MHz, CDCl3) 6,76 (l,J=9,1, 2H), 6,69 (d, 9,1, 2H), 4.00 points (t,J=5,9, 2H), 3,60 (t,J=6,6, 2H), 2,23 (m,J=6,1, 2H).

Example 5

4-(2-bromacil)phenol

2Cl2(3×50 ml). The combined extracts were dried, filtered and concentrated under reduced pressure to obtain 72 g (crude yield substances 100%) solids brownish-yellow color.1H NMR (400 MHz, CDCl3): a 9.25 (s, 1H),? 7.04 baby mortality (l,J=8,4, 2H), 6,67 (l,J=8,4, 2H), 3,62 (t,J=7,4, 2H), 2,97 (t,J=7,4, 2H).

Example 6

4-(3-bromopropyl)phenol

A mixture of 4-(3-hydroxypropyl)phenol (52.7 g, 346,3 mmol) in 48 wt.% HBr (265 ml) was stirred at 80°C for 20 h and then cooled to room temperature. Was added water (400 ml) and the product was extracted with CH2Cl2(500 ml). The extract was dried (MgSO4) and concentrated under reduced pressure to obtain the desired product in the form of a solid beige color (69 g, yield 92%). TLC (SiO2CH2Cl2): Rf=0,37.1H NMR (400 MHz, DMSO-d6): 9,18 (s, 1H), 6,99 (l,J=8,3, 2H), 6,67 (l,J=8,4, 2H), 3,47 (t,J=6,6, 2H), 2,58 (t,J=7,2, 2H), 2.05 is-of 1.95 (m, 2H).

Example 7

2-chloro-1-(2-trimethylsilylethynyl)-1H-benzoimidazol

To a suspension of sodium hydride (6.2 g, 245 mmol) in DMF (275 ml) at 5°C was added 2-orbiniidae (37 g, 243 mmol) via an addition funnel for solids within 30 minutes, maintaining the internal temperature of the mixture below 10°C. was Added an additional 25 ml of DMF and the ice bath was removed. After 2 h for 5 minutes was added dropwise 2-(trimethylsilyl)ethoxymethylene (S-CI). The resulting white precipitate formed. The reaction mixture was stirred at room temperature for 18 hours To the mixture was added H2O (500 ml) and ethyl acetate (750 ml). The organic layer was washed with additional amount of H2O (500 ml), dried (MgSO4) and concentrated under reduced pressure, getting 65.8 g (yield 96%) of the desired product as a clear oil, Golden color, which was aterials when standing with the formation of solid beige color. TLC (SIO, SIS2with 5% acetone/CH2Cl2): Rf=0,64. Mass spectrum (ESI): mass calculated for C13H19ClN2OSi; 282,10; m/z found 283,1.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=7,3, 1H), 7,46 (l,J=7,6, 1H), 7,40-7,25 (m, 2H), to 3.58 (t,J=7,9, 2H), 0,92 (t,J=8,3, 2H), and 0.04 (s, 9H).

Example 8

2-chloro-1-methyl-1H-benzoimidazol

Dimethylsulfate (11,0 ml, 116 mmol) was added to a solution of 2-chlorobenzimidazole (10.6 g, 70 mmol) in 2,5M Paon (70 ml, 175 mmol) and the mixture was stirred at 23°C for 2 h, the Reaction mixture was filtered, the solid product was washed H 2O (6×50 ml) and dried in vacuum to obtain solid light brown color (9.4 g, yield 81%). Mass spectrum (ESI): mass calculated for C8H7ClN2; 166,03; m/z found 167,0 [M+H]+.1H-NMR (400 MHz, CDCl3): 7,75-of 7.70 (m, 1H), 7,35-7,29 (m, 3H), 3,82 (s, 3H).

Example 9

2-[4-(2-bromoethoxy)phenoxy]benzothiazole

A solution of 4-(2-bromoethoxy)phenol (example 3; 8.7 g, 40,1 mmol) and 2-chlorobenzothiazole (12 ml, 92 mmol) in CH3SP worked fine powder Cs2CO3(26 g, 80 mmol) and the resulting mixture was stirred at 23°C for 30 h, the Reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The crude solid was purified on SIO, SIS2(100 g; 0-40% ethyl acetate/hexane) to give 6.7 g (yield 47%) as a solid white color. Mass spectrum (ESI): mass calculated for C15H12BrNO2S; 348,98; m/z found 350,0 [M+H]+.1H NMR (400 MHz, CDCl3): 7,78, (DD,J=8,0, 0,4, 1H), of 7.70 (DD,J=8,0, 0,7, 1H), 7,42 (dt,J=7,5, 1,3, 1H), 7,34 (DD,J=9,1, 2H), 7,01 (DD,J=9,1, 2H), 4,34 (t,J=6,2,2H), 3,70 (t,J=6,2, 2H).

Example 10

2-[4-(2-bromacil)phenoxy]benzothiazole

A. 2-[4-(benzothiazol-2-yloxy)phenyl]ethanol.

A solution of 4-hydroxyphenethyl alcohol (867 mg, 6.3 mmol) and 2-chlore is satiate (of 0.82 ml, 6.3 mmol) in CH3SP worked fine powder Cs2CO3(4.1 g, 12.5 mmol) and the resulting suspension was stirred for 40 h at 70°C. the Reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated to obtain the crude oil, which was purified on SIO, SIS2(40 g; 0-50% ethyl acetate/hexane)to give 940 mg (yield 55%) of a clear oil. Mass spectrum (ESI): mass calculated for C15H13NO2S; 271,07; m/z found 272,2 [M+H]+.1H NMR (400 MHz, CDCl3): for 7.78 (DD,J=7,9, 0,4, 1H), of 7.75 (DD,J=7,9, 0,7, 1H), 7,46 (dt,J=7,4, 1,3, 1H), 7,38-7,29 (m, 3H), 3,93 (kV,J=6,4, 2H), 2,94, (t,J=6,5, 2H), 1,50 (m, 1H).

C. 2-[4-(2-bromacil)phenoxy]benzothiazole.

A solution of 2-[4-(benzothiazol-2-yloxy)phenyl]ethanol (174 mg, 0.64 mmol) in benzene (3 ml) was treated with RVG3(to 0.060 ml, 0.64 mmol) and the resulting suspension was heated to 70°C for 90 minutes. The reaction mixture was cooled and was diluted with ethyl acetate (30 ml). The solution was washed H2O (10 ml), then saturated salt solution (10 ml), dried and concentrated under reduced pressure. The crude product was purified on SIO, SIS2(12 g; 0-50% ethyl acetate/hexane) and received 120 mg of oil is light yellow in color. Mass spectrum (ESI): mass calculated for C15H12BrNOS; 332,98; m/z found 335,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,79 (DD,J=8,0, 0,3, 1H), 7,76 (DD,J=8,0, 0,6, 1H), 7,42 (dt,J=7,4, 1,2, 1H), 7,8-7,29 (m, 3H), 3,62 (t,J=to 7.5, 2H), 3,25 (t,J=to 7.5, 2H).

Example 11

2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzooxazol

A. 1-[2-(4-(benzyloxyphenyl)ethyl]piperidine.

To a mixture of 4-(benzyloxy)phenol (24.6 g, 123 mmol) and hydrochloride of 1-(2-chloroethyl)piperidine (20.6 g, 112 mmol) in DMF (175 ml) was added To a2CO3(25 g, 181 mmol) and Cs2CO3(40 g, 123 mmol). The reaction mixture was stirred at room temperature for 3 days. To the mixture was added H2O (300 ml) and CH2Cl2. The organic layer was washed with 10% Paon, then a saturated solution of salt, dried (MgSO4), filtered and concentrated under reduced pressure to obtain 33 g of a transparent dark purple liquid. The liquid was purified on SIO, SIS2(300 g; 0-50% ethyl acetate/hexane) and got to 23.4 g (yield 67%) solid light yellow color. TLC (SIO, SIS2, 50% hexane/ethyl acetate): Rf=0,11. Mass spectrum (ESI): mass calculated for C20H25NO2; 311,19; m/z found 312,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50-7,26 (m, 5H), 6,91 (l,J=9,2, 2H), 6,85 (l,J=9,2, 2H), 5,02 (s, 2H), 4,06 (t,J=6,1, 2H), was 2.76 (t,J=6,1, 2H), of 2.51 (Sirs, 4H), 1,65-of 1.55 (m, 4H), 1,45 (Sirs, 2H).

Century 4-(2-piperidine-1-ylethoxy)phenol.

To a solution of 1-[2-(4-(benzyloxyphenyl)ethyl]piperidine (15.0 g, 48.2 mmol) in a mixture of ethanol/ethyl acetate, 1:1 (400 ml) was added Pd on coal (10 wt.%, 1,5g). The mixture was placed in hydrogenator Parra under pressure 40 psi H2for 20 hours. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 9.4 g (yield 88%) of the desired product as a solid light gray. TLC (SIO, SIS2, 50% acetone/CH2Cl2): Rf=0,16. Mass spectrum (ESI): mass calculated for C13H19NO2; 221,14; m/z found 222,1 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,88 (s, 1H), 6.73 x (l,J=6,6, 2H), 6,65 (l,J=6,6, 2H), 3,93 (t,J=6,0, 2H), 2,58 (t,J=6,0, 2H), 2.40 a (s, 4H), 1,51-of 1.45 (m, 4H), 1,35 (Sirs, 2H).

C. 2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzooxazol.

To a stirred solution of 4-(2-piperidine-1-ylethoxy)phenol (1.5 g, 6.8 mmol) in acetone (20 ml) at 5°C was added To the2CO3(1.0 g, 7.2 mmol). To the mixture was added 2-chlorobenzoxazole (0.5 ml, 4.4 mmol) at 5°C. the resulting mixture was heated to room temperature over night. After 20 hours the mixture was filtered and the filtrate was concentrated under reduced pressure to obtain solid brown color, which was purified on SIO, SIS2(35 g; 50% acetone/CH2Cl2). The desired fractions were combined and concentrated under reduced pressure to obtain 1.2 g (yield 80%) of the desired product in the form of a solid white color. TLC (SIO, SIS2, 50% acetone/CH2/sub> Cl2): Rf=0,18. Mass spectrum (ESI): mass calculated for C20H22N2About3; 338,16; m/z found 339,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,52 (d,J=7,2, 1H), 7,41 (l,J=7,2, 1H), 7,35-7,20 (m, 4H), 6,97 (l,J=9,1, 2H), 4,12 (t,J=6,1, 2H), and 2.79 (t,J=6,0, 2H), 2,52 (s, 4H), 1,67-of 1.55 (m, 4H), 1,50-of 1.40 (m, 2H).

Example 12

{2-[4-(6-chlorobenzothiazole-2-yloxy)phenoxy]ethyl}diethylamin

A. [2-(4-(benzyloxyphenyl)ethyl]diethylamine.

To a mixture of 4-(benzyloxy)phenol (51 g, 255 mmol) and hydrochloride (2-chloroethyl)diethylamine (41,6 g, 242 mmol) in DMF (400 ml) was added To a2CO3(37 g, 268 mmol) and Cs2CO3(87 g, 267 mmol). The reaction mixture was stirred at room temperature for 17 days. To the mixture was added H2O (600 ml) and CH2Cl2. The organic layer was washed H2O, dried (MgSO4), filtered and concentrated under reduced pressure to obtain 33 g of a transparent dark purple liquid, which was purified on SIO, SIS2(300 g; ethyl acetate), obtaining the oil is light yellow in color (34,5 g, yield 48%). TLC (SIO, SIS2, 50% hexane/ethyl acetate): Rf=0,10. Mass spectrum (ESI): mass calculated for C19H25NO2; 299,19; m/z found to 300.2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50-7,28 (m, 5H), 6.89 in (q,J=9,2, 2H), 6,85 (l,J=9,2, 2H), 5,02 (s, 2H), 4.00 points (t,J=6,4, 2H), 2,86 (t,J=6,4, 2H), 2.63 in (kV,J=7,2,4H), a 1.08 (t,J=7,1, 6H).

Century 4-(2-diethylaminoethoxy)phenol.

To a solution of [2-(4-(benzyloxyphenyl)ethyl]diethylamine (21 g, 70 mmol) in a mixture of ethanol/ethyl acetate, 1:1 (500 ml) was added Pd on coal (10 wt.%, 1.5 g). The mixture was placed in hydrogenator Parra under pressure 40 psi H2for 20 hours. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 13.1 g (yield 89%) of the desired product as a clear oil brown. Mass spectrum (ESI): mass calculated for C12H19NO2; 209,14; m/z found 210,2 [M+H]+.1H NMR (400 MHz, CDCl3): of 6.68 (s, 4H,), 3,99 (t,J=6,2, 2H), 2,88 (t,J=6,2, 2H), 2,69 (kV,J=7,2, 4H), of 1.09 (t,J=7,1, 6H).

C. {2-[4-(6-chlorobenzothiazole-2-yloxy)phenoxy]ethyl]diethylamine.

To a solution of 4-(2-diethylaminoethoxy)phenol (500 mg, 2,39 mmol) in acetone (7 ml)containing Cs2CO3(876 mg, 2,69 mmol), was added 2,6-dichlorobenzothiazole (365 mg, to 1.79 mmol). The resulting mixture was boiled under reflux for 3 days. The reaction mixture was filtered, the filtrate was concentrated under reduced pressure and the obtained brown oil, which was purified on SIO, SIS2(35 g; acetone) to give 624 mg (yield 76%) of the desired product. TLC (SIO, SIS2, acetone): Rf=0,23. Mass spectrum (ESI): mass calculated for C19H21ClN2About2S; 376,10; mz found 377,1 [M+H] +.1H NMR (400 MHz, CDCl3): to 7.64 (d,J=8,5, 2H), 7,34 (l,J=8,8, 1H), 7,25 (l,J=6,8, 2H), of 6.96 (d,J=9,1, 2H).

Example 13

(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol

A. 4-[2-(4-hydroxyethylpiperazine-1-yl)ethoxy]phenol.

A solution of 4-(2-bromoethoxy)phenol (example 3, 7 g is 32.2 mmol), piperidinemethanol (5,2 g of 45.3 mmol) and N,N-diisopropylethylamine (7.9 ml of 45.3 mmol) in CH3SP (100 ml) was stirred at 65°C for 18 hours the Reaction mixture was cooled to room temperature and stirred additional 48 hours the Solvent was removed under reduced pressure and got a black semi-solid substance. The resulting material was dissolved in CH2Cl2(200 ml) and the solution washed with H2O (2×50 ml). The aqueous phase was subjected to back extraction with 10% CH3HE/CH2Cl2(100 ml). The organic layers were combined, dried (Na2SO4), filtered and concentrated under reduced pressure to get oil black, which was purified on SIO, SIS2(120 g; 0-100% acetone/CH2Cl2)to give the desired product as brown oil. Oil, for precipitation of the product, was added diethyl ether. After the filter has been specified in the title compound in the form of solids brownish yellow (1.9 g, yield 23%). TLC (SIO, SIS2with 5% 2M NH3 in CH3HE/CH2Cl2): Rf=0,09. Mass spectrum (ESI): mass calculated for C14H21NO3; 251,15; m/z found 252,3 [M+H]+.1H NMR (400 MHz, CDCl3): 6,69 (s, 4H), a 4.03 (t,J=5,9, 2H), 3,51 (l,J=6,5, 2H), 3,09 (l,J=11,6, 2H), and 2.79 (t,J=5,9, 2H), 2,18-2,11 (m, 2H), 1,79 (l,J=16,2, 2H), 1,49-of 1.62 (m, 1H), 1,36 (DKV,J=3.6V, 12,3, 2H), 1,23 (Sirs, 2H).

C. (1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol.

A mixture of 4-[2-(4-hydroxyethylpiperazine-1-yl)ethoxy]phenol (0.5 g, to 1.98 mmol), 2-chlorobenzoxazole (205 μl, 1.8 mmol) and Cs2CO3(1.35 g, 4,15 mmol) in acetone (8.0 ml) was stirred at room temperature for 48 hours the mixture was filtered through kieselguhr and the layer was washed CH2Cl2. The combined filtrates were concentrated under reduced pressure and the obtained yellow oil. The oil was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2) and received solid, which was dissolved in CH2Cl2(100 ml). The solution was washed for 1H. Paon (3×5 ml) and then H2O (5 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to obtain specified in the connection header in the form of a solid white color (424 mg, yield 64%). TLC (SIO, SIS2with 5% 2M NH3in CH3HE/CH2Cl2): Rf=0,17. Mass spectrum (ESI): mass calculated for C21H24N2About 4; 368,17; m/z found 369,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,53 is 7.50 (m, 1H), 7,44-7,42 (m, 1H), 7,34-7,21 (m, 4H), 7,00-of 6.96 (m, 2H), 4,13 (t,J=6,0, 2H), 3,55-of 3.48 (m, 2H), 3,02-to 3.09 (m, 2H), 2,82 (t,J=6,0, 2H), 2,13 (dt,J=2,4, 11,8, 2H), 1,78 is 1.75 (m, 2H), 1,59 is 1.48 (m, 2H), 1,33 (DKV,J=3,7, 12,4, 2H).

Example 14

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol

A. 1-[2-(4-hydroxyphenoxy)ethyl]piperidine-4-ol.

To a stirred solution of 4-(2-bromoethoxy)phenol (example 3, 9 g, 42 mmol) in CH3SP (150 ml) was added 4-hydroxypiperidine (5.3g, 52,5 mmol) and then N,N-diisopropylethylamine (6.7 g, is 52.5 mmol). The resulting solution was stirred overnight at room temperature to obtain a suspension. The suspension was filtered and the filtrate was concentrated under reduced pressure. To the obtained oil was added diethyl ether and the mixture was heated to 45°C for 2 minutes with the formation of a white precipitate. The resulting suspension was stirred at room temperature for 2 hours, then filtered and obtained 7.9 g (33 mmol, yield 79%) not quite white solid. Mass spectrum (ESI): mass calculated for C13H19NO3; 237,14; m/z found 238,2 [M+H]+.1H NMR (400 MHz, CD3OD): 7,10 and 7,02 (kV,J=32,3, 9,0, 2H), 4,35 (t,J=5,7, 2H)and 3.59 (m, 1H), 3,26-3,19 (m, 2H), of 3.07 (t,J=5,7, 2H), 2,60 (t,J=9,9, 2H), 2,20-2,12 (m, 2H), 1,94-to 1.82 (m, 2H).

Century 1-{2-[4-(Bento Sasol-2-yloxy)phenoxy]ethyl}piperidine-4-ol .

To a stirred solution of 1-[2-(4-hydroxyphenoxy)ethyl]piperidine-4-ol (500 mg, 2.1 mmol) in acetone (10 ml) was added Cs2CO3(1.4 g, to 4.41 mmol). The resulting suspension was cooled to 0°C. and was added dropwise 2-chlorobenzoxazole (388 mg, 2.5 mmol, 0,29 ml). The reaction mixture was left to warm to room temperature overnight, then filtered and concentrated under reduced pressure. The resulting oil was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2) and received 400 mg (1.1 mmol, yield 54%) solid white. Mass spectrum (ESI): mass calculated for C20H22N2About4; 354,16; m/z found 355,2 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.55 (DD,J=7,2, 1,8, 1H), 7,46 (DD,J=7,3, 2,0, 1H), was 7.36 (d,J=9,1, 2H), 7,32-7,25 (m, 2H), 7,01 (l,J=9,1, 2H), 4,18 (t,J=5,4, 2H), 3,80 (m, 1H), 3,01-of 2.86 (m, 4H), 2.40 a (Sirs, 1H), 1,99 (m, 2H), 1,74-of 1.65 (m, 2H), 1,48 (l,J=4,1, 1H).

Example 15

1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol

To a stirred solution of 1-[2-(4-hydroxyphenoxy)ethyl]piperidine-4-ol (example 14, step A, 500 mg, 1.25 mmol) in DMF (10 ml) was added Cs2CO3(1.4 g, to 4.41 mmol) and 2-chlorobenzothiazole (0.33 ml, 2.5 mmol). The suspension was heated to 80°C and was stirred overnight. The reaction mixture was left to cool to room temperature and then filtered through Kisel the R. The filtrate was concentrated under reduced pressure and the residue was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2), getting 321 mg (0.86 mmol, yield 69%) solids brownish-yellow color. Mass spectrum (ESI): mass calculated for C20H22N2About3S; 370,14; m/z found 371,2 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.64 (d,J=8,0, 1H), 7,56 (l,J=7,8, 1H), 7,30 (m,J=7,2, 1H), 7,21-7,14 (m, 3H), 6.87 in (q,J=9,1, 2H), 4,05 (t,J=5,8, 2H), 3,67 (Sirs, 1H), 2,82 (m, 2H), was 2.76 (t,J=5,8, 2H), and 2.27 (t,J=9,5, 2H), 2,01 (Sirs, 1H), 1,90-to 1.82 (m, 2H), 1,64-of 1.52 (m, 2H).

Example 16

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dibutylamine

A. 4-(2-dibutylaminoethanol)phenol.

To a stirred solution of 4-(2-bromoethoxy)phenol (example 3, and 8.2 g, 37 mmol) in CH3SP (150 ml) was added dibutyltin (5,98 g, and 46.3 mmol) and N,N-diisopropylethylamine (5,98 g, and 46.3 mmol). The mixture was stirred overnight at 75°C. the resulting suspension was filtered and the filtrate was concentrated under reduced pressure. The resulting oil was purified on SIO, SIS2(110 g; 0-100% acetone/CH2Cl2)to give 7.7 g (29 mmol, yield 78%) solid brown color. Mass spectrum (ESI): mass calculated for C16H27NO2; 265,2; m/z found 266,2 [M+H]+.1H NMR (400 MHz, CDCl3): for 6.81 (d,J=7,0, 2H), 6,63 (l,J=6,0, 2H), 4,22 (Sirs, 2H), 3,25 (Sirs, 2H), 2,93 (width is, 4H), 2,16 (Sirs, 2H), 1,88 (Sirs, 1H), 1,68 (Sirs, 4H), 1,33 (l,J=5,7, 4H), 0,94 (Sirs, 6H).

Century {2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dibutylamine.

To a stirred solution of 4-(2-dibutylaminoethanol)phenol (500 mg, 1.9 mmol) in acetone (9.4 ml) was added Cs2CO3(1.3 g, 3.9 mmol). The resulting suspension was cooled to 0°C. and was added dropwise 2-chlorobenzoxazole (346 mg, 2.2 mmol, 0.26 per ml). The reaction mixture was left to warm to room temperature overnight and then filtered. The filtrate was concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2)to give 180 mg (0.47 mmol, yield 25%) solid white. Mass spectrum (ESI): mass calculated for C23H30N2About3; 382,23; m/z found 383,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50 (d,J=7,2, 2H), 7,41 (l,J=7,3, 2H), 7,31 (l,J=9,1, 2H), 7,28-7,19 (m, 2H), of 6.96 (d,J=9,1, 2H), 4,13 (m, 2H), 2,88 (m, 2H), 2,54 (m, 4H), of 1.47 (m, 4H), 1,32 (m, 4H), to 0.92 (t,J=7,3, 6H).

Example 17

Ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid

A. Ethyl ester 1-[2-(4-hydroxyphenoxy)ethyl]piperidine-4-carboxylic acid.

To a stirred solution of 4-(2-bromoethoxy)phenol (example 3, 5 g of 23.1 mmol) in CH3SP (200 ml) was added utility ecotat (5,3 ml, to 34.7 mmol). The reaction mixture was heated to 84°C., was stirred for 16 hours, then cooled to room temperature and concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(300 g; 0-25% acetone/CH2Cl2), getting a solid white color (6.3 g, yield 93%). Mass spectrum (ESI): mass calculated for C16H23NO4; 293,16; m/z found 294,3 [M+H]+.1H NMR (400 MHz, CDCl3): 6,63 (m, 4H), 4,07 (kV,J=7,2, 2H), 3.96 points (t,J=5,7, 2H), 2,96 (m, 2H), 2,74 (t,J=5,6, 2H), 2.26 and-of 2.23 (m, 3H), of 1.88-1.77 in (m, 5H), 1,17 (t,J=7,2, 3H).

C. Ethyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid.

To a stirred solution of ethyl ester 1-[2-(4-hydroxyphenoxy)ethyl]piperidine-4-carboxylic acid (2.5 g, 6.8 mmol) in CH3JV (34 ml) was added Cs2CO3(5 g, and 14.3 mmol) and 2-chlorobenzothiazole (1,26 ml, 10.2 mmol). The reaction mixture was heated to 75°C for 3 h, then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure. The residue was dissolved in CH2Cl2and was purified on SIO, SIS2(40 g; 0-25% acetone/CH2Cl2), getting a solid white color (2,94 g, yield 100%). Mass spectrum (ESI): mass calculated for C23H26N2About4S; 426,16; m/z found 427,1 [M+H]+.1H NMR (400 MHz, CDCl ): 7,76 (l,J=8,0, 1H), to 7.64 (t,J=8,1, 1H), 7,41 (t,J=8,4, 1H), 7,30 (m,J=9,0, 3H), 7,05 (l,J=6,8, 2H), 4,19 (t,J=5,5, 2H), 4,12 (kV,J=7,1, 2H), to 3.02 (m, 2H), and 2.83 (t,J=5,5, 2H), is 2.37 (m, 1H), 2,25 (t,J=11,6, 2H), 1.93 and (m, 2H), 1,79 (m, 2H), 1,24 (t,J=7,2, 3H).

Example 18

Potassium salt of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid

To a stirred solution of ethyl ester 1-{2-[4-benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid (example 17; 235 mg, 0.5 mmol) in THF (2.5 ml) was added triethylsilane potassium (282 mg, 2.2 mmol). The reaction mixture was stirred at room temperature for 2 hours and then concentrated under reduced pressure. The resulting oil was dissolved in H2O and the solution was treated with 1M HCl to pH 9. The resulting solution was extracted with a mixture of isopropyl alcohol/chloroform, 1:3 (3×25 ml). The combined extracts were concentrated under reduced pressure and obtained a brownish-yellow solid, which was triturated with diethyl ether. After filtration of the suspension was received solid brownish-yellow (140 mg, yield 64%). Mass spectrum (ESI): mass calculated for C21H22N2About4S (free acid), m/z calculated 398,13; m/z found 399,1 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,01 (l,J=7,3, 1H), 7,76 (l,J=to 7.5, 1H), 7,51 (t,J=8,4, 1H), ,45 (l, J=9,0, 2H), 7,40 (t,J=7,2, 1H), 7,14 (l,J=9,0, 2H), 4,18 (t,J=5,5, 2H), 2.95 and (m, 2H), 2,74 (t,J=5,8, 2H), 2,10 (t,J=10,5, 2H), is 1.81 (m, 2H), 1,59 (m, 2H).

Example 19

(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-1-ylmethanone

To a suspension of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid (example 18; 100 mg, 0.25 mmol) in Cl3(2 ml) was added oxalicacid (132 μl, 1.5 mmol). The reaction mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure. The obtained solid substance resuspendable in CHCl3(2 ml) was added pyrrolidine (100 μl, 1.2 mmol). The resulting solution was stirred for 1 hour, then diluted with CH2Cl2(10 ml) and washed with saturated aqueous Panso3(10 ml). The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure to obtain a yellow oil. The crude oil was purified on SIO, SIS2(10 g; 0-100% acetone/CH2Cl2)to give the desired product as a colourless oil (71 mg, yield 63%). Mass spectrum (ESI): mass calculated for C23H29N3About3S; 451,19; m/z found 452,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=7,6, 1H), 7,66 (DD,J=8,0, 0,8, 1H), 7,41-7,37 (m, 1H), 7,29-7,24 (m, 3H), 6,99-of 6.96 (m, 2H), 4,13 (t,J=6,0, 2H), 3,50 is-3.45 (m, 4H), 3,10 totaling 3.04 (m, H), and 2.83 (t,J=6,0, 2H), 2,38-2,31 (m, 1H), 2.21 are to 2.14 (m, 2H), 1,98-of 1.84 (m, 6H), 1,74-1,71 (m, 2H).

Example 20

Ethyl ester of 3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid

The hydrate of 1-hydroxybenzotriazole (NOUT; 1.0 ml, 0.5 m in DMF, 0.5 mmol), ethyl ester of 3-aminopropionic acid (120 mg, 0,785 mmol) and the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI; 150 ml, 0,785 mmol) sequentially at intervals of 5 minutes was added to a stirred suspension of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid (example 18; 210 mg of 0.53 mmol) in CH2Cl2(3 ml). The resulting mixture was stirred at room temperature overnight. The reaction mixture was diluted with CH2Cl2(10 ml), washed with saturated aqueous Panso3(10 ml) and then H2O (10 ml). The organic layer was dried (Na2SO4), filtered and concentrated under reduced pressure to get not quite a white solid. The crude residue was purified on SIO, SIS2(35 g; 0-5% 2M NH3in CH3HE/CH2Cl2), obtaining the desired product in the form of a solid white color (186 mg, yield 48%). Mass spectrum (ESI): mass calculated for C25H31N3About5S; 497,20; m/z found 498,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (DD,J=8,1, 0,6, 1H), 7,66 (the d, J=8,1, 0,8, 1H), 7,39 (dt,J=7,4, 1,3, 1H), 7,29-7,24 (m, 3H), 7,01-6,94 (m, 2H), 6,18-x 6.15 (m, 1H), 4,19-4,11 (m, 4H), 3,53 (kV,J=6,0, 2H), 3,06 totaling 3.04 (m, 2H), 2,81 (t,J=5,9, 2H), 2,53 (t,J=6,0, 2H), 2,18-to 2.06 (m, 3H), 1,88-1,72 (m, 4H), 1.28 (in t,J=7,2, 3H).

Example 21

(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol

A. {1-[2-(4-(benzyloxyphenyl)ethyl]piperidine-2-yl}methanol.

To a stirred solution of 2-(4-benzyloxyphenyl)ethylbromide (example 1; 7.0 g, of 22.8 mmol) and piperidine-2-ylmethanol (3,3 g, 28.7 mmol) in CH3CN (100 ml) was added To a2CO3(7,1 g, 51,4 mmol). The mixture was boiled under reflux for 20 hours and then filtered. The filtrate was concentrated under reduced pressure to obtain a clear oil, Golden color, which was purified on SIO, SIS2(120 g; 0-100% acetone/CH2Cl2)to give 6.0 g (yield 77%) solid white. TLC (SIO, SIS2, acetone): Rf=0,15. Mass spectrum (ESI): mass calculated for C21H27NO3; 341,20; m/z found 342,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.48-7,25 (m, 5H), 6,92 (l,J=9,1, 2H), 6,85 (l,J=9,1, 2H), 5,02 (s, 2H), to 4.38 (t,J=5,3, 2H), 3.96 points (t,J=6,2, 2H), 3,55-of 3.48 (m, 1H), 3.43 points-of 3.32 (m, 1H), 3,15-3,00 (m, 1H), 2,88-to 2.85 (m, 1H), 2,75-2,62 (m, 1H), 2,30-2,22 (m, 2H), 1.61 of (l,J=9,4, 2H), 1,52-of 1.44 (m, 1H), 1,44 to 1.31 (m, 1H), 1,30-1,17 (m, 2H).

Century 4-[2-(2-hydroxyethylpiperazine-1-yl)ethoxy]phenol.

To a solution of {1-[2-(4-(baie is siocsifname)ethyl]piperidine-2-yl}methanol (6.0 g, 17.6 mmol) in a mixture of ethanol/ethyl acetate, 1:1, (75 ml) was added Pd on coal (10 wt.%, 614 mg). The mixture was placed in hydrogenator Parra under pressure 40 psi H2for 20 hours. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 4.5 g (yield 100%) of the desired product as a clear and colorless oil. TLC (SIO, SIS2, acetone): Rf=0,29. Mass spectrum (ESI): mass calculated for C14H21NO3; 251,15; m/z found 252,3 [M+H]+.1H NMR (400 MHz, CD3OD): 6,77 (l,J=6,6, 2H), 6,68 (l,J=6,6, 2H), 4,06-4,01 (m, 2H), 3,70-3,55 (m, 2H), 3,22-3,10 (m, 1H), 3,05-2,96 (m, 1H), 2,88-and 2.79 (m, 1H), 2,47-of 2.36 (m, 2H), 1,76 is 1.70 (m, 2H), 1,63-of 1.32 (m, 4H).

C. (1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethoxy}piperidine-2-yl)methanol.

A mixture of 4-[2-(2-hydroxyethylpiperazine-1-yl)ethoxy]phenol (197 mg, 0.78 mmol), 2-chlorobenzoxazole (116 μl, of 1.02 mmol) and Cs2CO3(700 mg, of 2.15 mmol) in acetone (10 ml) was stirred at room temperature for 20 hours the mixture was filtered through diatomaceous earth. Layer was washed with acetone and the combined filtrates were concentrated under reduced pressure, getting a Golden oil. The oil was purified on SIO, SIS2(10 g; 0-100% acetone/CH2Cl2) to give the desired product as a clear and colorless oil (202 mg, 70%). TLC (SIO, SIS2, acetone): Rf=0,17. Mass spectrum (ESI): mass calculated DL is 21H24N2About3S; 384,15; m/z found 369,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.61 (d,J=7,0, 2H), 7,50 (d,J=7,0,2H), 7,41 (l,J=9,1, 4H), 7,35-7,30 (m, 4H), 7,03 (l,J=9,1, 4H,), to 4.41 (t,J=5,3, 2H), 4,07 (t,J=6,2, 4H), 3,60-to 3.52 (m, 2H), 3,44-to 3.35 (m, 2H), 3,18-is 3.08 (m, 2H), 2,90-to 2.85 (m, 2H), 2,78-of 2.72 (m, 2H), 2,35-of 2.28 (m, 4H), 1,62 (l,J=9,2, 4H), 1,53 to 1.47 (m, 2H), 1,47 is 1.34 (m, 2H), 1.32 to of 1.18 (m, 4H).

Example 22

Amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid

A suspension of 2-[4-(2-bromoethoxy)phenoxy]benzothiazole (example 9; 200 mg, or 0.57 mmol), isonipecotamide (73 mg, or 0.57 mmol) and dimethylamino resin Silicycle® (800 mg, to 1.14 mmol) in CH3CN was heated to 70°C for 18 hours the Reaction mixture was filtered and the collected resin was washed CH3CN. The combined filtrates were concentrated under reduced pressure and obtained crude solid, which was purified on SIO, SIS2(10 g; 0-100% 10% [2M NH3in CH3HE] CH2Cl2/CH2Cl2) to obtain 142 mg (yield 63%) solid white. Mass spectrum (ESI): mass calculated for C21H23N3About3S; 397,15; m/z found 398,4 [M+H]+.1H NMR (400 MHz, CDCl3): a 7.85 (DD,J=8,0, 0,3, 1H), of 7.75 (DD,J=8,0, 0,6, 1H), 7,42 (DD,J=7,4, 1,1, 1H), 7,32-7,22 (m, 3H), 7,02-6,91 (m, 2H), 5,67 (shirt,J=47, 2H), 4,15 (t,J=5,8, 2H), 3,09 (shirt,J=8,8, 2H), 2,85 (t,J=5,7, 2H), 2,28-2,1 (m, 3H), 2.00 in a 1.88 (m, 2H), 1,87-1,72 (m, 2H).

Example 23

1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he

A suspension of 2-[4-(2-bromoethoxy)phenoxy]benzothiazole (example 9; 200 mg, or 0.57 mmol), hydrochloride of 1-piperidine-4-iparralde-2-she (117 mg, or 0.57 mmol) and dimethylamino resin Silicycle® (800 mg, to 1.14 mmol) in CH3CN was heated to 70°C for 18 hours the Reaction mixture was filtered and the collected resin was washed CH3CN. The combined filtrates were concentrated under reduced pressure and obtained crude solid, which was purified on SIO, SIS2(10 g; 0-100% 10% [2M NH3in CH3HE] CH2Cl2/CH2Cl2with getting not quite sticky white solid (142 mg, yield 63%). Mass spectrum (ESI): mass calculated for C24H27N3About3S; 337,18; m/z found 348,5 [M+H]+.1H NMR (400 MHz, CDCl3): a 7.85 (DD,J=8,0, 0,5, 1H), of 7.75 (DD,J=8,0, 0,8, 1H), 7,41 (dt,J=7,3, 1,5, 1H), 7,34-7,22 (m, 3H), 7,02-6,92 (m, 2H), 4,15 (shirt,J=48,8, 2H), 3,80-the 3.65 (m, 1H), 3,40 (t,J=7,0, 1H), 3,30-3,10 (Sirs, 1H), 3.15, the (kV, J=7,2, 1H), 2,96 {Sirs, 1H), 2,42, (t,J=7,9, 2H), 2,10-1,99 (m, 1H), 1,81 is 1.70 (m, 1H) 1,68-of 1.52 (m, 4H), 1.50 in (q,J=6,5, 3H).

Example 24

1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he

To a stirred solution of 2-[4-(2-bromoethoxy)phenoxy]benzodiaz the La (example 9; 542 mg, 1.55 mmol) and hydrochloride [1,4']bipiperidine-2-it (371 mg, was 1.69 mmol) in CH3CN (20 ml) was added To a2CO3(517 mg, 3,74 mmol). The mixture was boiled under reflux for 20 hours and then filtered. The filtrate was concentrated under reduced pressure to obtain a clear oil, Golden color, which was purified on SIO, SIS2(10 g; 0-100% acetone/CH2Cl2)to give 294 mg (yield 42%) as a solid white color. TLC (SIO, SIS2, acetone): Rf=0,15. Mass spectrum (ESI): mass calculated for C25H29N3O3S; 451,19; m/z found 452,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=1,1, 2H), of 7.90 (d,J=1,1, 2H), 7,42 (t,J=7,3, 2H), 7,37 (l,J=9,0, 2H), 7,31 (t,J=7,3 2H), 7,06 (l,J=9,0, 2H), 4,32-is 4.21 (m, 1H), 4,10 (t,J=5,7, 2H), 3.15 in (t,J=5,3, 2H), 3.00 and (l,J=11,5, 2H), 2,71 (t,J=5,7, 2H), 2,21 (t,J=6,5, 2H), 2,10 (t,J=11,4, 2H), 1,75 is 1.58 (m, 6H), 1,43 (l,J=10,0, 2H).

Example 25

8-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2,8-diaza-Spiro[4.5]Decan-1-he

A suspension of 2-[4-(2-bromoethoxy)phenoxy]benzothiazole (example 9; 257 mg, 0.73 mmol), hydrochloride 2,8-diaza-Spiro[4.5]Decan-1-she (153 mg, 0.80 mmol) and dimethylamino resin Silicycle® (1.7 g, 2.4 mmol) in CH3CN was heated up to 80°C for 18 hours the Reaction mixture was filtered and the collected resin was washed CH3CN. The combined filtrates concentri is ovali under reduced pressure and obtained crude solid, which was purified on SIO, SIS2(10 g; 0-100% 10% [2M NH3in CH3HE] CH2Cl2/CH2Cl2with getting not quite white solid (152 mg, yield 49%). Mass spectrum (ESI): mass calculated for C23H25N3About3S; 423,16; m/z found 424,2 [M+H]+.1H NMR (400 MHz, CDCl3): for 7.78 (DD,J=8,1, 0,6, 1H), 7,69 (DD,J=8,0, 0,8, 1H), 7,41 (dt,J=7,5, 1,3, 1H), 7,32-7,27 (m, 3H), 7,00 (m, 2H), 6,36 (Sirs, 1H), 4,15 (t,J=5,9, 2H), 3,36 (t,J=7,0, 2H), 3.00 and, (dt,J=11,9, 3,9, 2H), 2,87 (t,J=5,8, 2H), 2,32 (dt,J=11,5, 2,4, 2H), 2,10-to 1.98 (m, 2H), 2,07 (t,J=7,0, 2H), 1,50 (shirt,J=13,3, 2H).

Example 26

2-[4-(3-pyrrolidin-1 ipropose)phenoxy]benzothiazole

A. 1-[3-(4-(benzyloxyphenyl)propyl]pyrrolidin.

To a mixture of 1-[3-(4-benzyloxyphenyl)propyl]bromide (example 2; 1.50 g, 4.7 mmol) was added pyrrolidine (2.0 ml, 24,0 mmol) in CH3CN. The mixture was stirred for 20 h and then concentrated under reduced pressure to obtain a yellow oil, which was purified on SIO, SIS2(35 g; acetone)to give 1.2 g (yield 80%) of the desired product in the form of a solid white color. TLC (SIO, SIS2, acetone): Rf=0,05. Mass spectrum (ESI): mass calculated for C20H25NO2; 311,19; m/z found 312,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50-7,30 (m, 5H), 6.90 to (q,J=9,1, 2H), PC 6.82 (d,J=9,1, 2H), 5,02 (s, 2H), 4.00 points (t,J=6,1, 2H), from 3.0 to 2.75 (m, 6H), 2,15 (is, J=6,2, 2H), 1,94 (Sirs, 4H).

Century 4-(3-pyrrolidin-1 ipropose)phenol.

To a solution of 1-[3-(4-(benzyloxyphenyl)propyl]pyrrolidine (1.2 g, 3.9 mmol) in a mixture of ethanol/ethyl acetate, 1:1, (65 ml) was added Pd on coal (10 wt.%, 206 mg). The mixture was placed in hydrogenator Parra under pressure 40 psi H2for 20 hours. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 875 mg (yield 100%) of the desired product as a brown solid. Mass spectrum (ESI): mass calculated for C13H19NO2; 221,14; m/z found to 222.2 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 8.90 (s, 1H), 6,74 (l,J=9,0, 2H), 6,65 (l,J=9,0, 2H), 3,90 (t,J=6,3, 2H), 2,72 (Sirs, 6H), 1,90 (quintet,J=7,4, 2H), 1,76 (s, 4H).

C. 2-[4-(3-pyrrolidin-1 ipropose)phenoxy]benzothiazole.

To a stirred solution of 4-(3-pyrrolidin-1 ipropose)phenol (100 mg, 0.45 mmol) in acetone (10 ml)containing Cs2CO3(213 mg, of 0.65 mmol), was added 2-chlorobenzothiazole (65 μl, 0.50 mmol). The mixture was boiled under reflux for 24 h and then filtered. The filtrate was concentrated under reduced pressure and obtained a clear oil, Golden color, which was purified on SIO, SIS2(10 g; 0-100% acetone) to give 97 mg (yield 61%) of the desired product. TLC (SIO, SIS2, acetone): Rf=0,02. Mass spectrum (ESI): mass calculated for C 20H22N2About2S; 354,14; m/z found 355,1 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,73 (d, 1H), 6,95 (d, 1H), 7,39 (m, 1H), 7,26 (m, 3H), of 6.96 (d,J=9,1, 2H), 4,06 (t,J=6,4, 2H), 2,65 (t,J=7,3, 2H), 2,55 (Sirs, 4H), 2,04 (quintet,J=6,5, 2H), 1,82 (Sirs, 4H).

Example 27

1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol

A. the hydrobromide 1-[3-(4-(hydroxyphenoxy)propyl]-4-phenylpiperidine-4-ol.

4-(3-bromopropane)phenol (example 4; 3 g, 13 mmol) was dissolved in CH3CN (65 ml). To the solution was added 4-hydroxy-4-phenylpiperidine (6.8 g, 39 mmol) and the mixture was stirred at room temperature overnight, obtaining a white precipitate. The suspension was filtered and received specified in the title compound in the form of solid white (5 g, to 11.9 mmol, yield 91%). Mass spectrum (ESI): mass calculated for C20H25NO3(free base), m/z calculated 327,18; m/z found 328,2 [M+H]+.1H NMR (400 MHz, CD3OD): 7,49 (l,J=to 7.5, 2H), 7,32 (t,J=to 7.5, 2H), 7,21 (t,J=7,2, 1H), 6.73 x (kV,J=12,3, 4H), 3.96 points (t,J=6,1, 2H), 2,85 (l,J=11,3, 2H), 2,64-of 2.54 (m, 4H), 2.13 in (dt,J=9,0, 3,9, 2H), 2,00 (m, 2H), 1.75 of (l,J=12,2, 2H).

Century 1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol.

To a stirred solution of the hydrobromide of 1-[3-(4-hydroxyphenoxy)propyl]-4-phenylpiperidine-4-ol (500 mg, 1.5 mmol) in acetone (7 ml) d is balali Cs 2CO3(1,03 g and 3.15 mmol). The resulting suspension was cooled to 0°C. and was added dropwise 2-chlorobenzoxazole (276 mg, 1.8 mmol, 0.2 ml). The reaction mixture was heated to room temperature overnight, then filtered and concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2) to obtain 450 mg (1.05 mmol, yield 70%) solid white. Mass spectrum (ESI): mass calculated for C25H26N2O4; 444,20; m/z found 445,20 [M+H]+.1H NMR (400 MHz, CD3OD): 7,47-the 7.43 (m, 3H), of 7.36-7,11 (m, 8H), 6.90 to (q,J=9,1, 2H), 3,99 (t,J=5,8, 2H), 2,80 (l,J=9,5, 2H), 2,56 (t,J=6,8 Hz, 2H), 2,44 (t,J=10,9, 2H), 2.13 in (t,J=11,0, 2H), up to 1.98 (m,J=6,8, 2H), 1,71 (l,J=6,9, 2H).

Example 28

1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol

A. 4-benzyl-1-[3-(4-(hydroxyphenoxy)propyl]piperidine-4-ol.

4-benzyl-4-hydroxypiperidine (750 mg, 3.9 mmol) was added to a solution of 4-(3-bromopropane)phenol (example 4; 300 mg of 1.31 mmol) in CH3CN (6 ml). The reaction mixture was stirred at room temperature over night and got a white precipitate. The suspension was filtered and the filtrate was concentrated under reduced pressure. The resulting oil was purified on SIO, SIS2(10 g; 0-100% acetone/CH2Cl2with the floor is rising 110 mg (0.32 mmol, yield 25%) solid white. Mass spectrum (ESI): mass calculated for C21H22NO3; 341,20; m/z found 342,2 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.36-7,24 (m, 3H), 7,22 (l,J=6,9, 2H), 6,7 (m, 4H), 4,07 (t,J=6,5, 2H), 3,41 (l,J=11,7, 2H), 3,19 (t,J=7,8, 2H), 3,11 (t,J=11,8, 4H), 2,84 (Sirs, 2H), 2,34 (Sirs, 4H), 2,18 (Sirs, 1H), 1,72 (d, 14.5 m, 2H).

Century 1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol.

To a stirred solution of 4-benzyl-1-[3-(4-(benzyloxyphenyl)propyl]piperidine-4-ol (2.5 g, 7,3 mmol) in acetone (37 ml) was added Cs2CO3(4,99 g of 15.3 mmol). The resulting suspension was cooled to 0°C. and was added dropwise 2-chlorobenzoxazole (1.1 ml, 9.5 mmol). The reaction mixture was heated to room temperature overnight, then filtered and concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(110 g; 0-100% acetone/CH2Cl2) to obtain 310 mg (0.67 mmol, yield 9%) solid white. Mass spectrum (ESI): mass calculated for C28H30N2O4; 458,2; m/z found 459,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,49 (l,J=7,2, 1H), 7,41 (l,J=7,2, 1H), 7,35-to 7.18 (m, 9H), 6,94 (l,J=9,1, 2H), Android 4.04 (t,J=6,5, 2H), 2.93 which is 2.45 (m, 7H), of 2.16 (s, 4H), 1,60 (l,J=13,0, 2H), 1,29 (Sirs, 1H).

Example 29

2-[4-(2-piperidine-1-retil)phenoxy]benzooxazol

A. 4-(2-piperidine-1-retil)phenol.

A solution of 4-(2-bromacil)phenol (example 5, and 4.5 g of 22.4 mmol), piperidine (3.3 ml of 33.5 mmol) and N,N-diisopropylethylamine (5.8 ml, of 33.5 mmol) in CH3SP (100 ml) was stirred at 60°C for 18 h the resulting solution was cooled to room temperature and concentrated under reduced pressure to obtain a light orange solid. Added diethyl ether (100 ml) and indicated in the title compound was collected by filtration as not quite white solid (4.6 g, yield of the crude substances 100%). TLC (SIO, SIS2with 5% 2M NH3in CH3HE/CH2Cl2): Rf=0,19. Mass spectrum (ESI): mass calculated for C13H19NO2; 205,15; m/z found 206,1 [M+H]+.1H NMR (400 MHz, CD3OD): 7,07? 7.04 baby mortality (m, 2H), 6,74-of 6.71 (m, 2H), 3,32-3,30 (m, 2H), 3,14-3,11 (m, 3H), 2,87 is 2.80 (m, 1H), 1,82-to 1.67 (m, 6H), 1,65-of 1.55 (m, 2H).

C. 2-[4-(2-piperidine-1-retil)phenoxy]benzooxazol.

A mixture of 4-(2-piperidine-1-retil)phenol (0.5 g, 2,43 mmol), 2-chlorobenzoxazole (304 μl, to 2.67 mmol) and Cs2CO3(1.8 g, 5,62 mmol) in acetone (10 ml) was stirred at room temperature for 48 hours the Reaction mixture was filtered through kieselguhr and the layer was washed CH2Cl2. The combined filtrates were concentrated under reduced pressure and got an orange oil, which was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2obtaining the desired product in the form of a solid white color (325 mg, yield 42%). TLC (SIO, SIS2with 5% 2M NH3in CH3HE/CH2Cl2): Rf=0,36. Mass spectrum (ESI): mass calculated for C20H22N2About2; 322,17; m/z found 323,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,53-7,51 (m, 1H), 7,44-7,42 (m, 1H), 7,34-7,20 (m, 6H), 2,87-and 2.83 (m, 2H), 2,60-of 2.56 (m, 2H), 2,48 (Sirs, 2H), 1,66-to 1.59 (m, 6H), 1,50 was 1.43 (m, 2H).

Example 30

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine

A. 4-[2-(cyclohexylamino)ethyl]phenol.

To a stirred solution of 4-(2-bromacil)phenol (example 5, 4,48 g of 22.3 mmol) in CH3SP (100 ml) was added cyclohexylethylamine (5.0 ml, 33.4 mmol) and then N,N-diisopropylethylamine (7,76 ml and 44.6 mmol). The resulting solution was stirred at 60°C for 16 h and received a suspension. The resulting suspension was left to cool to room temperature and filtered. The filtered solid was washed with ethyl acetate (2×20 ml) and dried to obtain solid white (4.8 g, yield 87%). Mass spectrum (ESI): mass calculated for C16H25NO; 247,19; m/z found 248,2 [M+H]+.1H NMR: (400 MHz, CDCl3): 7,01 (l,J=8,6, 2H), 6.87 in (q,J=8,6, 2H), 3,32-3,17 (m, 2H), 3.15 and are 2.98 (m, 4H), 2,30-of 2.21 (m, 2H), 1.77 in-to 1.59 (m, 2H), 1,57 of 1.46 (m, 5H), 1,40-1,10 (m, 3H).

Century {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine.

To a stirred solution of 1-[2-(4-(hydroxyphenoxy)ethyl]piperidin-4-ol (495 mg, 2.0 mmol) in DMF (10 ml) was added Cs2CO3(1.3 g, 4.0 mmol) and 2-chlorobenzothiazole (0.33 ml, 2.5 mmol). The suspension was stirred at 80°C during the night. The reaction mixture was left to cool to room temperature and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the residue was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2with getting 548 mg (yield 72%) solids brownish-yellow color. Mass spectrum (ESI): mass calculated for C23H28N2OS; 380,19; m/z found 381,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,63 (l,J=8,0, 1H), 7,30 (m,J=8,0, 1H), 7,29-7,20 (m, 5H), 2,78 of 2.68 (m, 4H), 2,62 (DD,J=6,8, 7,4, 2H), 2,56 is 2.46 (m, 1H), 1,83-of 1.74 (m, 4H), 1,66-of 1.57 (m, 1H), 1,21 (DD,J=9,0, 8,6, 4H), 1,15-1,11 (m, 1H), 1.06 a (t,J=7,2, 3H).

Example 31

Amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid

A suspension of 2-[4-(2-bromacil)phenoxy]benzothiazole (example 10;, 250 mg, 0.75 mmol), nipecotate (96 mg, 0.75 mmol) and dimethylamino resin Silicycle® (1.1 g, 1.50 mmol) in CH3CN was heated to 70°C for 18 hours the Reaction mixture was filtered and the collected resin was washed CH3CN. The combined filtrates were concentrated under reduced pressure and obtained crude solid, which was purified on SIO, SIS2(10 g; 0-100% 10% [2M NH3in CH3HE] the N 2Cl2/CH2Cl2) to obtain 135 mg (yield 47%) solid white. Mass spectrum (ESI): mass calculated for C21H23N3About2S; 381,15; m/z found 382,4 [M+H]+.1H NMR (400 MHz, CDCl3): 8,10 (l,J=8,1, 1H), of 7.75 (DD,J=8,0, 0,8, 1H), 7,42 (dt,J=7,4, 1,3, 1H), 7,21 (Sirs, 1H) 6.42 per (Sirs, 1H), 3,05 (shirt,J=10,3, 1H), 2.95 and is 2.80 (m, 3H), 2,80-2,62 (m, 2H), 2,47-to 2.40 (m, 1H), 2,36 (l,J=11,5, 1H), 2,08 (t, J=10,5, 1H), 1,98 (l,J=11,0, 1H), 1,76-to 1.63 (m, 1H), 1,63 of 1.50 (m, 2H).

Example 32

1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-methyl-1,3-dehydrobenzperidol-2-he

A. 2-[4-(benzothiazol-2-yloxy)phenyl]ethyl ester toluene-4-sulfonic acid.

To a stirred solution of 2-[4-(2-benzothiazol-2-yloxy)phenyl]ethanol (example 10; 12,25 g of 45.2 mmol) in CH2Cl2(225 ml) was added p-toluensulfonate (17,23 g, 90 mmol) and tea (31 ml, 225 mmol). The resulting mixture was stirred at room temperature for 72 h, the Reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate (400 ml). The solution was washed with saturated aqueous Panso3(3×200 ml), dried (Na2SO4) and concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(300 g; CH2Cl2with getting solid brownish-yellow C the ETA (8.8 g, yield 45%). Mass spectrum (ESI): mass calculated for C22H19N3About4S2; 425,08; m/z found 426,0 [M+H]+.1H NMR (400 MHz, CDCl3): 7,70 (kV,J=9,7, 4H), 7,39 (t,J=7,8, 1H), 7,32-7,17 (m, 8H), 4,23 (t,J=6,9, 2H), 2,99 (l,J=6,9, 2H), 2,43 (s, 3H).

Century 1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-methyl-1,3-dehydrobenzperidol-2-it.

To a stirred solution of 2-[4-(benzothiazol-2-yloxy)phenyl]ethyl ester toluene-4-sulfonic acid (400 mg, of 0.94 mmol) in CH3CN (5 ml) was added 1-methyl-3-piperidine-4-yl-1,3-dehydrobenzperidol-2-he (653 mg, 2.82 mmol). The reaction mixture was stirred at room temperature overnight, then concentrated under reduced pressure and was purified on SIO, SIS2(12 g; 50% acetone/CH2Cl2with getting a clear oil (16 mg, yield of 3.3%). Mass spectrum (ESI): mass calculated for C28H28N4About2S; 484,19; m/z found 485,5 [M+H]+.1H NMR (400 MHz, CD3OD): 7,75 (l,J=7,9, 1H), 7,65 (l,J=8,1, 1H), 7,41-7,29 (m, 7H), 7,13 (m, 3H), 4,37 (m, 1H), 3,40 (s, 3H), 3,25 (l,J=11,8, 2H), equal to 2.94 (m, 2H), 2,75 (m, 2H), 2.57 m (qud,J=12,6, 3,7, 2H), 2,33 (t,J=11,3, 2H), 1,81 (l,J=12,2, 2H).

Example 33

Methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

A. Methyl ester 1-[2-(4-hydroxyphenyl)ethyl]piperidine-4-carboxylic acid.

To stir a solution of 4-(2-bromacil)phenol (example 5, of 5.05 g, 25 mmol) in CH3SP (100 ml) was added methyl ether piperidine-4-carboxylic acid (5,07 ml, 37.5 mmol) and then N,N-diisopropylethylamine (8.7 ml, 50 mmol). The reaction mixture was stirred at 60°C for 16 h and then left to cool to room temperature. Added CH2Cl2(250 ml) and the resulting solution was washed with H2O (2×30 ml), dried, filtered and concentrated under reduced pressure to obtain 5.2 g (79%) solids brownish-yellow color. Mass spectrum (ESI): mass calculated for C15H21NO3; 263,15; m/z found 264,3 [M+H]+.1H NMR (400 MHz, CDCl3): 6,97 (l,J=8,2, 2H), 6,70 (l,J=8,6, 2H), 3,67(with,3H), 2,99 (l,J=11,5, 2H), was 2.76 of 2.68 (m, 2H), 2,60-of 2.54 (m, 2H), 2.40 a-2,30 (m, 1H), 2,18 (t,J=10,8, 2H), 1,99-1,90 (m, 2H), 1,90-of 1.78 (m, 2H).

Century, Methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid.

To a stirred solution of methyl ester 1-[2-(4-hydroxyphenyl)ethyl]piperidine-4-carboxylic acid (790 mg, 3.0 mmol) in DMF (15 ml) was added Cs2CO3(of 1.95 g, 6.0 mmol) and 2-chlorobenzothiazole (of 0.47 ml, 3.9 mmol). The suspension was heated to 100°C. and was stirred overnight. The reaction mixture was left to cool to room temperature and filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the residue was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2 ) to obtain 1.04 g (yield 87%) solids brownish-yellow color. Mass spectrum (ESI): mass calculated for C23H24N2About3S; 396,15; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=7,8, 1H), 7,65 (l,J=7,8, 1H), 7,38 (t,J=7,6, 1H), 7,28-7,25 (m, 5H), of 3.69 (s, 3H), 3.00 and-of 2.93 (m, 2H), and 2.83 (DD,J=7,6, 3,0, 2H), 2,61 (DD,J=7,6, 3,0, 2H), 2,38-of 2.28 (m, 1H), 2,11 (t,J=10,4, 2H), 1,98-1,89 (m, 2H), 1,87-of 1.74 (m, 2H).

Example 34

(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-(4-methylpiperazin-1-yl)methanon

A. Trifurcata salt 1-

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid.

To a solution of methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid (example 33; 4.6 g, 11.7 mmol) in a mixture of THF/CH3HE 3:1 (100 ml) was added lithium hydroxide (1.1 g, with 46.6 mmol) in H2O (25 ml). Dark yellow solution was stirred at room temperature for 16 h and then concentrated under reduced pressure. The residue was dissolved in CH3HE and purified HPLC with reversed phase with obtaining specified in the connection header in the form of a solid light-yellow color (3,9 g, yield 68%). Mass spectrum (ESI): mass calculated for C21H22N2About3S; 382,14; m/z found 383,4 [M+H]+.

C. (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}Pipa is one-4-yl)-(4-methylpiperazin-1-yl)methanon.

To the mixture FA-salt 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid (300 mg, 0.6 mmol) in CH2Cl2(15 ml) and one drop of DMF was added oxalicacid (of 0.11 ml, 1.2 mmol). The mixture was stirred at room temperature for 1 h the mixture was concentrated under reduced pressure. The residue was dissolved in CH2Cl2(15 ml) was added N-methylpiperazine (0.2 ml, 1.8 mmol). The reaction mixture was stirred at room temperature for 1 hour, diluted with CH2Cl2(100 ml), washed with H2O, saturated aqueous Panso3(10 ml) and then with saturated salt solution, dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure and the residue was purified on SIO, SIS2(40 g; 0-10% 2M NH3in CH3HE/CH2Cl2), getting mentioned in the title compound (240 mg, 86%). Mass spectrum (ESI): mass calculated for C26H32N2About3S; 464,22; m/z found 465,5 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,72 (l,J=7,6, 1H), 7,65 (l,J=7,6, 1H), 7,37 (t,J=7,6, 1H), 7,29-7,22 (m, 5H), 3,64 (Sirs, 2H), 3,51 (Sirs, 2H), 3,06 (l,J=11,4, 2H), and 2.83 (DD,J=7,3, 3,5, 2H), 2,60 (DD,J=7,3, 3,5, 2H), of 2.51 is 2.43 (m, 1H), 2,42 is 2.33 (m, 4H), of 2.30 (s, 3H), 2.06 to (t,J=12,1, 2H), 1,99-of 1.84 (m, 2H), 1,72 (l,J=13,1, 2H).

Example 35

{3-[4-(benzooxazol-2-yloxy)phenyl]propyl} - cyclohexylamine the

A. [3-(4-benzyloxyphenyl)propyl]cyclohexylethylamine.

To a solution of 3-(4-benzyloxyphenyl)propyl-1-bromide (504 mg, of 1.65 mmol) and N-ethylcyclohexylamine (497 μl, 3,30 mmol) in CH3CN (15 ml) was added To a2CO3(510 mg, of 3.69 mmol). The reaction mixture is boiled under reflux for 20 hours. The mixture was filtered and then concentrated under reduced pressure to get a Golden oil, which was purified on SIO, SIS2(10 g; 50% acetone/CH2Cl2), getting 484 mg (yield 83%) of the desired product as a clear and colorless oil. TLC (SIO, SIS2, acetone): Rf=0,13. Mass spectrum (ESI): mass calculated for C24H33NO; 351,26; m/z found 352,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50-7,28 (m, 5H), 7,12 (l,J=8,6, 2H), 6.90 to (q,J=8,6, 2H), is 5.06 (s, 2H), 2,60 at 2.45 (m, 7H), 1,78 (Sirs, 6H), 1,20 (Sirs, 4H), of 1.05 (t,J=7,1, 4H).

Century 4-[3-(cyclohexylamino)propyl]phenol.

To a solution of [3-(4-(benzyloxyphenyl)propyl]cyclohexylethylamine (420 mg, 1,19 mmol) in a mixture of ethanol/ethyl acetate, 1:1, (16 ml) was added Pd on coal (10 wt.%, 46 mg). The mixture was placed in hydrogenator Parra under pressure 40 psi H2for 20 hours. The resulting mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 308 mg (yield 99%) of the desired product in the form of oil is Golden in color. TLC (SIO, SIS2, acetone): Rf=0,18 Mass-spectrum (ESI): mass, calculated for C17H27NO; 261,21; m/z found 262,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,00 (l,J=8,5, 2H), 6.75 in (q,J=8,5, 2H), 2,65 (Sirs, 5H), of 2.54 (t,J=7,6, 2H), 1,82 (Sirs, 6H), 1.30 and of 1.05 (m, 8H).

C. {3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclohexylethylamine.

To a mixture of 4-[3-(cyclohexylamino)propyl]phenol (283 mg, of 1.08 mmol) and Cs2CO3(885 mg, of 2.72 mmol) in acetone (15 ml) at 5°C was added 2-chlorobenzoxazole (155 μl, of 1.36 mmol). The reaction mixture was left to slowly warm to room temperature overnight and then filtered. The filtrate was concentrated under reduced pressure to get a Golden oil, which was purified on SIO, SIS2(10 g; acetone) to give 333 mg (yield 81%) of the desired product in the form of oil is Golden in color. TLC (SIO, SIS2, acetone): Rf=0,12. Mass spectrum (ESI): mass calculated for C24H30N2About2; 378,23; m/z found 379,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.61 (d,J=7,3, 1H), 7,49 (l,J=7,8, 1H), 7,39 (l,J=8,6, 2H), 7,38-7,25 (m, 4H), 2,62 (t,J=to 7.5, 2H), 2,65 to 2.35 (m, 8H), 1,67(Sirs, 5H), 1,19-1,10 (m, 4H), of 0.95 (t,J=7,1, 3H).

Example 36

1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}piperidine-4-ol

A. 1-[3-(4-hydroxyphenyl)propyl]piperidine-4-ol.

A solution of 4-(3-bromopropyl)phenol (example 6, 1.42 g, 6.6 mmol), hydrochloride 4-hydroxypiperidine (908 is g, 6.6 mmol) and N,N-diisopropylethylamine (2.2 ml, 12.3 mmol) in CH3SP (20 ml) was stirred at 60°C for 18 hours the Reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure to get not quite a white solid. The resulting material was dissolved in CH2Cl2(200 ml), the solution washed with H2O (2×50 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to obtain solid white. Added diethyl ether and indicated in the title compound collected by filtration (1.4 g, yield 90%). TLC (SIO, SIS2with 5% 2M NH3in CH3HE/CH2Cl2): Rf=0,05. Mass spectrum (ESI): mass calculated for C14H21NO2; 235,16; m/z found 236,2 [M+H]+.1H NMR (400 MHz, CD3OD): of 6.96-6,94 (m, 2H), 6,64-of 6.61 (m, 2H), 3,89-3,82 (m, 1H), 3,29-3,20 (m, 4H), 3,02-2,95 (m, 4H), 2,52 (t,J=7,4, 2H), 1,95-to 1.87 (m, 4H), 1,68 is 1.60 (m, 2H).

Century 1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}piperidine-4-ol.

A mixture of 1-[3-(4-hydroxyphenyl)propyl]piperidine-4-ol (0.4 g, was 1.69 mmol), 2-chlorobenzoxazole (176 μl, 1.54 mmol) and Cs2CO3(1.45 g, of 4.45 mmol) in acetone (8.0 ml) was stirred at room temperature for 48 hours the mixture was filtered through diatomaceous earth and then washed CH2Cl2. The combined filtrates were concentrated under reduced pressure and got the aslo yellow. The oil was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2) and received a solid white substance, which was dissolved in CH2Cl2. The resulting solution was washed with 1M Paon (3×5 ml) and then H2O (5 ml), dried (Na2SO4), filtered and concentrated under reduced pressure to obtain specified in the connection header in the form of a solid white (98 mg, yield of 16.4%). TLC (SIO, SIS2with 5% 2M NH3in CH3HE/CH2Cl2): Rf=0,14. Mass spectrum (ESI): mass calculated for C21H24N2About3; 352,18; m/z found 363,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,66-7,51 (m, 1H), 7,44-7,42 (m, 1H), 7,34-7,21 (m, 6H), 3.72 points at 3.69 (m, 1H), 2,79 was 2.76 (m, 2H), to 2.67 (t,J=7,8, 2H), 2,38 (t,J=7,6, 2H), 2,15-2,11 (m, 2H), 1,98 and 1.80 (m, 3H), 1,65-of 1.55 (m, 3H), of 1.42 (m, 1H).

Example 37

1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol

A. 1-[2-(4-hydroxyphenoxy)ethyl]-4-phenylpiperidine-4-ol.

To a solution of 4-(2-bromoethoxy)phenol (example 3, 8.0 g, to 36.8 mmol) and 4-hydroxy-4-phenylpiperidine (8,2 g, and 46.3 mmol) in CH3SP (150 ml) was added DIEA (7.0 ml, with 40.2 mmol). The mixture was stirred for 20 hours at room temperature and an additional 4 hours at 65°C and then the mixture was concentrated under reduced pressure, obtaining a solid brown color. The solid was dissolved in etelaat is e (250 ml), the solution was washed H2O (250 ml, 100 mmol), dried (MgSO4) and concentrated under reduced pressure to obtain brown solid. The solid was purified on SIO, SIS2(120 g; 0-100% acetone/CH2Cl2) and received a 8.9 g (yield 77%) of the desired product in the form of a solid brownish-yellow color. TLC (SIO, SIS2, acetone): Rf=0,42. Mass spectrum (ESI): mass calculated for C19H23NO3; 313,17; m/z found 314,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,52 (d,J=8,6, 2H), 7,37 (t,J=7,3, 2H), 7,27 (m, 1H), 6.75 in (s, 4H), 4,08 (t,J=5,8, 2H), 3,05-2,90 (m, 2H), 2,88 (t,J=5,8, 2H), 2,80-2,62 (m, 2H), 2,31-to 2.18 (m, 2H), 1,81 (l,J=11,8, 2H).

Century 4-phenyl-1-(2-{4-[1-(2-trimethylsilylethynyl)-1H-benzoimidazol-2-yloxy]phenoxy}ethyl)piperidine-4-ol.

To a mixture of 2-chloro-1-(2-trimethylsilylethynyl)-1H-benzoimidazole (example 7; 630 mg, 2.2 mmol) and 1-[2-(4-hydroxyphenoxy)ethyl]-4-phenylpiperidine-4-ol (690 mg, 2.2 mmol) in DMF (10 ml) was added Cs2CO3(1.5 g, 4.6 mmol). The reaction mixture was stirred at 100°C for 18 h and then distributed in a mixture of ethyl acetate/H2O, 1:1, 50 ml). The organic layer was collected, dried (MgSO4) and concentrated under reduced pressure to obtain a transparent brown oil, which was purified on SIO, SIS2(35 g; acetone), getting 867 mg (yield 70%) of the desired product as a clear oil Golden is about color. TLC (SIO, SIS2, acetone): Rf=0,38. Mass spectrum (ESI): mass calculated for C32H41N3About4Si, m/z calculated 559,29; m/z found 560,3 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.55 (m, 3H), 7,38 (m, 3H), 7,30-7,20 (m, 5H), 6,99 (l,J=9,0, 2H), of 5.55 (s, 2H), 4,17 (t,J=5,9, 2H), 6,37 (m, 2H), 2,92 (m, 5H), 2,65 (t,J=12,4, 2H), 2,21 (t,J=15,9, 2H), 1,81 (l,J=12,1, 2H), 0,96 (t,J=8,1, 2H).

C. 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol.

To a solution of 4-phenyl-1-(2-{4-[1-(2-trimethylsilylethynyl)-1H-benzoimidazol-2-yloxy]phenoxy}ethyl)piperidine-4-ol (816 mg, of 1.46 mmol) in THF (5 ml)containing N,N,N,N-tetramethylethylenediamine (TMEDA, 2.2 ml, 14.6 mmol), was added 1M solution of tetrabutylammonium fluoride in THF (TBAF, 15 ml, 15 mmol). The mixture was stirred at 55°C for 5 hours and then concentrated under reduced pressure. The resulting oil was dissolved in diethyl ether (100 ml), the solution washed with H2O (3×75 ml), dried (MgSO4), filtered and concentrated under reduced pressure to obtain solid white. Added diethyl ether and after filtration was obtained the desired product in the form of a solid white color (155 mg, yield 25%). TLC (SIO, SIS2, acetone): Rf=0,16. Mass spectrum (ESI): mass calculated for C25H27N3About3m/z calculated 429,21; m/z found 430,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,23 (Sirs, 1H), of 7.48 (d,J=7,3, 2H), 7,35-7,25 (m, 6H), 7,20 (m,J=7,4, 1H), 7,10? 7.04 baby mortality (m, 2H), 7,00 (l,J=9,0, 2H), 4,80 (s, 1H), 4,13 (t,J=5,8, 2H), was 2.76 (t,J=5,8, 2H), 2,58-2,48 (m, 2H), was 1.94 (dt,J=12,7, 4,0, 2H), 1,58 (l,J=12,1, 2H).

Example 38

2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine

A. 4-[2-(cyclopropylamino)ethyl]phenol.

To a solution of 4-(2-bromacil)phenol (example 5; 5.0 g, 25,0 mmol) in CH3SP (100 ml) was added cyclopropanemethylamine (5,4 ml, 37.5 mmol) and then N,N-diisopropylethylamine (to 8.70 ml, 50.0 mmol). The resulting solution was stirred at 60°C for 16 h and received a suspension, which was cooled to room temperature and filtered. The filtered solid was washed with ethyl acetate (2×20 ml) and dried, obtaining a solid white color (5.7 g, yield 98%). Mass spectrum (ESI): mass calculated for C15H23NO; 233,18; m/z found 234,1 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,01 (l,J=8,6, 2H), 6.87 in (q,J=8,6, 2H), 3,34-3,30 (m, 2H), 3,19 totaling 3.04 (m, 2H), 2,94 is 2.75 (m, 4H), 1,75-of 1.56 (m, 2H), 1,16-0,99 (m, 1H), of 0.95-0.87 (m, 3H), 0,68-of 0.53 (m, 2H), 0,44-0,32 (m, 2H).

Century {2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine.

A mixture of 2-chloro-1-(2-trimethylsilylethynyl)-1H-benzoimidazole (example 7; 707 mg, 2.5 mmol), 4-[2-(cyclohexylethylamine)ethyl]phenol (467 mg, 2.0 mmol) and Cs2CO3(1.3 g, 4.0 mmol) in DMF (10 is l) was stirred at 100°C for 18 hours The reaction mixture was cooled to room temperature and then distributed in a mixture of ethyl acetate/H2O, 1:1 (200 ml). The organic layer was collected, dried (MgSO4) and concentrated under reduced pressure to obtain a transparent brown oil, which was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2), getting 729 mg (yield 76%) of a clear oil Golden brown. Mass spectrum (ESI): mass calculated for C28H41N3About2Si, m/z calculated 479,30; m/z found 480,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,63-7,58 (m, 1H), 7,49-7,39 (m, 1H), 7,31 (s, 4H), 7,26-7,22 (m, 2H), to 5.58 (s, 2H), 3,69 (t,J=8,2, 2H), 2,89-and 2.79 (m, 4H), 22,63-of 2.58 (m, 2H), 2,48 (l,J=6,5, 2H), 1,61 of 1.50 (m, 2H), 1,01-of 0.91 (m, 6H), 0,59-of 0.53 (m, 2H), 0.20 to 0.15 in (m, 2H), 0,1 (s, 9H).

C. 2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine.

To a solution of cyclopropylmethanol(2-{4-[1-(2-trimethylsilylethynyl)-1H-benzoimidazol-2-yloxy]phenyl}ethyl)amine (411 mg, 0.87 mmol) in THF (5 ml) syringe was added TBAF (1M in THF, to 2.57 ml, 2.57 mmol) and the mixture was stirred while boiling under reflux for 16 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The resulting oil was purified on SIO, SIS2(40 g; 0-20% CH3HE/CH2Cl2) and received 284 mg (yield 95%) of a clear oil. Mass spectrum (ESI): mass calculated for C22H27 N3Oh, m/z calculated 349,22; m/z found 350,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,34 (Sirs, 2H), 7.18 in-7,05 (m, 6H), 2,82-2,70 (m, 4H), 2,69-2,62 (m, 2H), 2,52 (l,J=6,8, 2H), 1,61 of 1.50 (m, 2H), of 0.91 (t,J=6,8, 4H), 0,57-of 0.51 (m, 2H), 0,16 (DD,J=5,3, 5,1, 2H).

Example 39

Cyclohexylethyl{2-[4-(1-methyl-1H-benzoimidazol-2-yloxy)phenyl]ethyl}amine

A mixture of 4-[2-(cyclohexylamino)ethyl]phenol (247 mg, 1.0 mmol), N-methylbenzimidazole (example 8; 200 mg, 1.2 mmol) and Cs2CO3(652 mg, 2.0 mmol) in DMF (3 ml) was stirred at 100°C for 16 hours, the Reaction mixture was cooled, filtered through diatomaceous earth and then washed with ethyl acetate (30 ml). The combined filtrates were washed in H2O (3×10 ml), then saturated salt solution (10 ml), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude substance was purified on SIO, SIS2(10 g; 0-100%, 10% [2M NH3in CH3HE] CH2Cl2/CH2Cl2) and received 105 mg (yield 28%) of brown oil. Mass spectrum (ESI): mass calculated for C24H31N3About; 377,53; m/z found 378,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,52 (d,J=7,2, 1H), 7,63-7,58 (m, 1H), 7,33-to 7.18 (m, 7H), 3.75 to(with,3H), 2,81-2,70 m, 4H), 2,68 (kV,J=7,1, 2H), 2,60-of 2.50 (m, 1H), 1,90 and 1.80 (m, 4H), 1,67 (l,J=12,3, 1H), 1,35-of 1.18 (m, 4H), 1,15-of 1.05 (m, 1H), 1,12 (t,J=7,1, 3H).

Example 40

1-{3-[4-(benzooxazol-2-yloxy)phenoxy]-2-hydroxypropyl}-4-phenylpiperidine-4-ol

A. 2-(4-(benzyloxyphenyl)oxiran.

To a solution of 4-(benzyloxy)phenol (15.0 g, 74.9 mmol) and epichlorohydrin (30 ml, 384 mmol) in DMF (200 ml) was added Cs2CO3(51,2 g, 157 mmol). The mixture was heated to 75°C for 3 days. The reaction mixture was cooled to room temperature and then distributed in a mixture of ethyl acetate/H2O, 1:1, (600 ml). The organic layer was collected, washed with H2O (3×250 ml), dried (MgSO4), filtered and concentrated under reduced pressure to obtain 38 g of a transparent dark brown liquid. The obtained liquid was purified on SIO, SIS2(300 g, 50-100% CH2Cl2/hexane) and was obtained the desired product in the form of a solid white (13 g, yield 68%). TLC (SIO, SIS2CH2Cl2): Rf=0,64.1H NMR (400 MHz, CDCl3): 7,55-7,28 (m, 5H), 6,91 (l,J=9,3, 2H), 6,86 (l,J=9,3, 2H), to 5.03 (s, 2H), 4,17 (DD,J=11,0, 3,2, 1H), 3.95 to 3,88 (m, 1H), 3,36-to 3.33 (m, 1H), 2.91 in (t,J=4,8, 1H), 2,75 (DD,J=4,9, 2,6, 1H).

C. 1-[3-(4-(benzyloxyphenyl)-2-hydroxypropyl]-4-phenylpiperidine-4-ol.

To a solution of 2-(4-(benzyloxyphenyl)oxirane (1.50 g, of 5.85 mmol) and 4-hydroxy-4-phenylpiperidine (1.30 grams, 7,33 mmol) in CH3JV (50 ml) was added To a2CO3(1.0 g, of 7.23 mmol). The mixture was boiled under reflux for 20 hours, the Reaction mixture was filtered and Phi is Trat concentrated under reduced pressure to obtain solid white, which was purified on SIO, SIS2(40 g; acetone)to give 1.4 g (yield 56%) of the desired product in the form of a solid white color. TLC (SIO, SIS2, acetone): Rf=0,36. Mass spectrum (ESI): mass calculated for C27H31NO4; 433,23; m/z found 434,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,56-of 7.23 (m, 10H), 6,93 (l,J=9,2, 2H), 6,88 (l,J=9,2, 2H), to 5.03 (s, 2H), of 4.77 (s, 2H), 3,93 (shirt,J=10,8, 2H), 3,81 (t,J=7,2, 1H), 2,80-2,60 (m, 2H), 2,50 to 2.35 (m, 4H), 1,97-1,90 (m, 2H), 1.60-to 1,50 (l,J=13,4, 2H).

C. 1-[2-hydroxy-3-(4-hydroxyphenoxy)propyl]-4-phenylpiperidine-4-ol.

To a solution of 1-[3-(4-(benzyloxyphenyl)-2-hydroxypropyl]-4-phenylpiperidine-4-ol (1.3 g, 3.0 mmol) in a mixture of ethanol/ethyl acetate, 1:1, 50 ml) was added Pd on coal (10 wt.%, 165 mg). The mixture was placed in hydrogenator Parra under pressure 40 psi H2for 20 hours. The reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain 1.0 g (yield 100%) of the desired product in the form of a solid white color. TLC (SIO, SIS2, acetone): Rf=0,27. Mass spectrum (ESI): mass calculated for C20H25NO4; 343,18; m/z found 344,3 [M+H]+.1H NMR (400 MHz, CD3OD): to 7.61 (d,J=8,1, 2H), 7,42 (t,J=7,4, 2H), 7,30 (m,J=7,3, 1H), 6.90 to (q,J=9,0, 2H), for 6.81 (d,J=9,0, 2H), 4,25 (Sirs, 1H), 4,05-3,95 (m, 2H), 3,10-of 2.92 (m, 2H), 2,80-2,60 (m, 4H), 2,30-of 2.20 (m, 2H), 1,81 (l,J=11,8, 2H).

D. 1-{3-[4-(benzooxazol-2-yloxy)fenoc and]-2-hydroxypropyl}-4-phenylpiperidine-4-ol .

To a mixture of 1-[2-hydroxy-3-(4-hydroxyphenoxy)propyl]-4-phenylpiperidine-4-ol (251 mg, 0.73 mmol) and Cs2CO3(667 mg, 2.05 mmol) in acetone (10 ml) at 5°C was added 2-chlorobenzoxazole (108 μl, 0.95 mmol). The reaction mixture was left on ice, was heated overnight to room temperature and then filtered. The filtrate was concentrated under reduced pressure to get a Golden oil, which was purified on SIO, SIS2(10 g; acetone) to give 127 mg (yield 38%) of the desired product in the form of a solid white color. TLC (SIO, SIS2, acetone): Rf=0,27. Mass spectrum (ESI): mass calculated for C27H28N2About5; 460,20; m/z found 461,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,60 (l,J=6,6, 1H), 7,55-to 7.35 (m, 5H), 7,32-7,25 (m, 4H), 7,20 (m,J=7,3, 1H), 7,06 (l,J=9,1, 2H), 4,78 (s, 1H), 4,10-of 3.85 (m, 3H), 2,80-to 2.65 (m, 2H), 2,55 to 2.35 (m, 4H), 1,95 (t,J=13,1, 2H), 1,59 (l,J=13,2, 2H).

Example 41

Ethyl ester of 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid

A. 4-benzooxazol-2-ylmethylene.

A mixture of 4-hydroxyphenylarsonic acid (35 g, 230 mmol) and 2-aminophenol (43 g, 400 mmol) was heated at 180°C for 3 hours and then cooled to room temperature. The obtained solid was crushed, was dissolved in THF (200 ml) and then added carbonyldiimidazole (27 g, 170 mmol). Astor was stirred at 60°C over night. The reaction mixture was concentrated under reduced pressure and was distributed between ethyl acetate (400 ml) and H2O (300 ml). The organic layer was concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(200 g; 0-50% acetone/CH2Cl2), receiving solid brown (31 g, yield 40%). Mass spectrum (ESI): mass calculated for C14H11NO2; 225,08; m/z found 226,1 [M+H]+.1H NMR (400 MHz, CD3OD): a 7.62 (m, 1H), 7,53 (m, 1H), 7,32 (m, 2H), 7,17 (l,J=8,5, 2H), 6.75 in (q,J=8,5, 2H), 4,18 (s, 2H).

C. 2-[4-(2-bromoethoxy)benzyl]benzooxazol.

To a stirred solution of 4-benzooxazol-2-ylmethylene (5 g, of 22.2 mmol) in CH3SP (100 ml) was added Na2CO3(6.4 g, with 46.6 mmol) and dibromoethane (7.9 ml, and 88.8 mmol). The resulting suspension was heated to 70°C for 72 hours and filtered while hot. The filtrate was concentrated under reduced pressure. The obtained solid is suspended in diethyl ether, filtered and then the filtrate was concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(110 g; CH2Cl2), receiving not quite white solid (1 g, the output of 13.7%). Mass spectrum (ESI): mass calculated for C16H14BrN2; 331,02; m/z found 332,0 [M+H]+.1H NMR (400 MHz, CD OD): a 7.62 (m, 1H), 7,53 (m, 1H), 7,34 (m, 2H), 7,29 (l,J=8,6, 2H), 6,92 (l,J=8,7, 2H), 4,28 (t,J=5,9, 2H), 4,23 (s, 2H), to 3.67 (t,J=5,9, 2H).

C. Ethyl ester 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid.

To a stirred solution of 2-[4-(2-bromoethoxy)benzyl]benzooxazole (0.5 g, 1.5 mmol) in CH3JV (7.5 ml) was added utilizedabated (0.7 ml, 4.5 mmol). The mixture was stirred at room temperature for 48 hours and then concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(40 g; 0-25% acetone/CH2Cl2), receiving the solid is not quite white (275 mg, yield 45%). Mass spectrum (ESI): mass calculated for C24H28N2About4; 408,20; m/z found 409,2 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.67 (m, 1H), 7,45 (m, 1H), 7,28 (l,J=9,0, 4H), to 6.88 (d,J=8,7, 2H), 4,20 (s, 2H), 4,12 (kV,J=7,1, 2H), 4,08 (t,J=5,9, 2H), 2.95 and (l,J=11,5, 2H), 2,77 (t,J=5,9, 2H), 2,24 (m, 1H), 2,16 (m, 2H), of 1.84 (m, 2H), 1,76 (m, 2H), 1,24 (t,J=7,2, 3H).

Example 42

Methyl ether of 1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid

A. 4-benzothiazol-2-ylmethylene.

A mixture of 4-hydroxyphenylarsonic acid (15.2 g, 100 mmol) and 2-aminobenzamide (10,7 ml, 100 mmol) was heated at 150°C for 16 hours and then cooled to room temperature. Receiving the Noah solid was ground and dissolved in CH 2Cl2(400 ml). The solution was washed for 1H. HCl (2×50 ml), then saturated aqueous Panso3(2×50 ml), dried, filtered and concentrated under reduced pressure. The residue was purified on SIO, SIS2(0-50% ethyl acetate/hexane)to give a solid white (10.5 g, yield 44%). Mass spectrum (ESI): mass calculated for C14H11NS; 241,06; m/z found 342,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,89 (DD,J=8,6, 4,8, 2H), 7,47 (t,J=7,8, 1H), 7,31 (t,J=7,8, 1H), 7,18 (l,J=8,3, 2H), 6,77 (l,J=8,6, 2H), 4,89 (s, 1H), 4,33 (s, 2H).

C. 2-[4-(2-bromoethoxy)benzyl]benzothiazole.

To a stirred solution of 4-benzothiazol-2-ylmethylene (10,5 g of 43.5 mmol) in CH3SP (100 ml) was added Cs2CO3(28,3 g, 87 mmol) and dibromoethane (18.7 ml, and 21.8 mmol). The resulting suspension was heated to 70°C for 16 hours, cooled to room temperature and then was dissolved in CH2Cl2(400 ml). The solution was washed H2O (2×50 ml), dried and concentrated. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(0-50% ethyl acetate/hexane)to give a solid white color (7.5 g, yield 49.5 per cent). Mass spectrum (ESI): mass calculated for C16H14BrNS; 347,00; m/z found 348,1 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.99 (d,J=8,1, 1H), 7,79 (l,J=8,1, 1H), 7,45 (t,J=7,6, 1H), was 7.36-7,25 (m, 3H), 6.89 in (q,J=8,8, 2H), to 4.38 (s, 2H), 4,28 (t,J=6,3, 2H), 3,63 (t,J=6,3, 2H).

C. Mei the new ester of 1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid .

To a stirred solution of 2-[4-(2-bromoethoxy)benzyl]benzothiazole (1.0 g, 2.9 mmol) in CH3SP (20 ml) was added methylisophthalic (0.7 ml, and 55.7 mmol) and N,N-diisopropylethylamine (1.5 ml, 8.6 mmol). The mixture was heated to 60°C for 16 h, cooled to room temperature and then was dissolved in CH2Cl2(100 ml). The solution was washed H2O (2×20 ml), dried and concentrated. The resulting oil was dissolved in CH2Cl2and was purified on SIO, SIS2(0-15% CH3HE/CH2Cl2), getting a solid white color (1.1 g, yield 92%). Mass spectrum (ESI): mass calculated for C23H26N2About3S; 410,17; m/z found 411,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,98 (l,J=8,3, 1H), 7,76 (l,J=8,3, 1H), 7,42 (t,J=7,8, 1H), 7,33-7,24 (m, 3H), 6,88 (l,J=8,8, 2H), 4,36 (s, 2H), 4,07 (t,J=6,1, 2H), 3,66 (s, 3H), 2,97-2,90 (m, 2H), was 2.76 (t,J=6,1, 2H, 2,33-of 2.24 (m, 1H), 2,15 (t,J=11,4, 2H), 1.93 and is 1.86 (m, 2H), 1,83-1,72 (m, 2H).

Example 43

Trifurcata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)propionic acid

A. Ethyl ester of 3-[2-(4-hydroxyphenoxy)ethylamino]propionic acid.

To a stirred solution of 4-(2-bromoethoxy)phenol (example 3, 2.4 g, 11 mmol) in CH3JV (50 ml) were added hydrochloride ethyl ester 3-aminopropionic acid (3.4 g, 22 mmol) and then N,N-diisopropylethylamine (7.7 ml, 44 the mol). The mixture was stirred at 60°C for 16 hours, left to cool to room temperature and then was dissolved in CH2Cl2(100 ml). The resulting solution was washed with H2O (2×15 ml), dried, filtered and concentrated under reduced pressure to obtain brown oil, which was used in the next stage.

C. Ethyl ester 3-{2-(4-benzothiazol-2-yloxy)phenoxy]ethylamino}propionic acid.

To a stirred solution of ethyl ester of 3-[2-(4-hydroxyphenoxy)ethylamino]propionic acid (11 mmol) in DMF (30 ml) was added Cs2CO3(10.8 g, 33 mmol) and 2-chlorobenzothiazole (2,72 ml, 22 mmol). The suspension was stirred at 100°C during the night. The reaction mixture was left to cool to room temperature and then filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and was purified on SIO, SIS2(100 g; 0-100% CH3HE/CH2Cl2)to give 1.9 g (yield 45%) of butter a light brown color. Mass spectrum (ESI): mass calculated for C22H22N2About4S, m/z calculated 386,13; m/z found 387,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,66 (l,J=8,1, 1H), 7,58 (l,J=8,3, 1H), 7,30 (m,J=7,8, 1H), 7,22-to 7.15 (m, 3H), 6,86 (l,J=9,1, 2H), 4.09 to (DD,J=7,1, 7,1, 2H), 4,01 (t,J=5,3, 2H), 2,98 (t,J=5,3, 2H), 2,92 (t,J=6,6, 2H), 2.49 USD (t,J=6,6, 2H), 2,20 (Sirs, 1H), 1,20 (t,J=7,1,3H).

C. Ethyl ester 3-({2-[4-(is isothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)propionic acid .

To a solution of ethyl ester of 3-{2-(4-benzothiazol-2-yloxy)phenoxy]ethylamino}propionic acid (500 mg, 1,29 mmol) in CH3HE (15 ml) was added acetic acid (0,73 ml, 12.9 mmol), molecular sieves 3Å and [(1-amoxicilpin)oxy]trimethylsilane (of 1.55 ml, 7.7 mmol). Added cyanoborohydride sodium (365 mg, 5.8 mmol) and the mixture is boiled under reflux during the night. The mixture was cooled, filtered and concentrated. The residue was dissolved in CH2Cl2obtained solution was washed with saturated aqueous Panso3and then with saturated salt solution, dried and concentrated. The residue was purified on SIO, SIS2(40 g; 10-50% ethyl acetate/hexane) and received 374 mg (yield 68%) of colorless oil. Mass spectrum (ESI): mass calculated for C23H26N2About4S, m/z calculated 426,16; m/z found 427,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,3, 1H), to 7.64 (d,J=8,1, 1H), 7,38 (d,J=7,8, 1H), 7,29-7,22 (m, 3H), 6,94 (l,J=9,1, 2H), 4,14 (DD,J=7,1, 7,1, 2H), 4,10 (t,J=6,1, 2H), of 3.07 (t,J=7,1, 2H), 3,05 (t,J=6,1, 2H), 2,58 (t,J=7,3, 2H), 1,92 is 1.86 (m, 1H), 1.26 in (t,J=7,1, 3H), 0,54-0,43 (m, 4H).

D. Trifurcata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino]propionic acid.

To a solution of ethyl ester of 3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)propionic acid (355 mg, 11.7 mmol) in THF (15 ml) and CH3HE (5 ml) was added hydroc the ID of lithium (80 mg, 3.3 mmol) in H2O (10 ml). The mixture was stirred at room temperature for 16 h and then concentrated under reduced pressure. The residue was dissolved in CH3HE and purified HPLC with reversed phase with obtaining specified in the title compound (391 mg, yield 92%). Mass spectrum (ESI): mass calculated for C21H22N2About4S; 398,13; m/z found 399,1 [M+H]+.1H NMR (400 MHz, CD3OD): 7,73 (l,J=8,3, 1H), to 7.64 (d,J=8,1, 1H), of 7.48 (d,J=7,8, 1H), 7,35-7,25 (m, 3H), 7,11 (l,J=9,1, 2H), 5,17 (Sirs, 1H), 4,48 (t,J=4,6, 2H), 3,81 (t,J=4,6, 2H), 3,76 (t,J=7,1, 2H), 3.04 from-of 2.93 (m, 3H), 1,17-1,10 (m, 2H), 1,05 is-0.97 (m, 2H).

Example 44

2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 11, using 1-(2-chloroethyl)pyrrolidine. Mass spectrum (ESI): mass calculated for C19H20N2About3; 324,15; m/z found 325,1 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.75 (d,J=8,1, 1H), 7,66 (l,J=8,0, 1H), 7,40 (dt,J=7,4, 1,3, 1H), 7,31-of 7.23 (m, 3H), 6,98 (l,J=6,8, 2H), 4,08 (t,J=6,3, 2H), 2.91 in (t,J=6,3, 2H), 2,67 (kV,J=7,2, 4H), 1,10 (t,J=7,2, 6H).

Example 45

{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}dimethylamine

Specified in the title compound was obtained in accordance with the methodology, opican the th in example 11, using hydrochloride (2-chloropropyl)dimethylamine. Mass spectrum (ESI): mass calculated for C18H20N2About3; 312,15; m/z found 313,1 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.48 was 7.45 (m, 1H), 7,40-7,38 (m, 1H), 7,30 (m,J=7,9, 2H), 7.23 percent-to 7.18 (m, 2H), 6,91 (l,J=8,3, 2H), 4.09 to (Sirs, 2H), 3,23 (Sirs, 2H), 2,85 (Sirs, 6H), 2,42 (Sirs, 2H).

Example 46

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dimethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 11, using hydrochloride (2-chloroethyl)dimethylamine. Mass spectrum (ESI): mass calculated for C17H18N2About3; 298,13; m/z found 299,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,49-7,47 (m, 1H), 7,41-7,38 (m, 1H), 7,32-7,27 (m, 2H), 7,26-to 7.18 (m, 2H), 6,98-to 6.95 (m, 2H), 4,05 (t,J=5,7, 2H), 2,72 (t,J=5,7, 2H), 2,32 (s, 6H).

Example 47

2-[4-(2-azepin-1 ylethoxy)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 11, using the hydrochloride of 1-(2-chloroethyl)azepane. Mass spectrum (ESI): mass calculated for C21H24N2About3; 352,18; m/z found 353,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,49-7,47 (m, 1H), 7,41-7,38 (m, 1H), 7,31-7,27 (m, 2H), 7,26-to 7.18 (m, 2H), 6,97-6,93 (m, 2H), 4,06 (t,J=6,2, 2H), 2,94 (t,J=6,2, 2H), 2.77-to a 2.75 (m, 4H), 1,65 is 1.58 (m,8H).

Example 48

{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dimethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 12, using hydrochloride (2-chloroethyl)dimethylamine and 2-chlorobenzothiazole. Mass spectrum (ESI): mass calculated for C17H18N2About2S; 314,11; m/z found 315,1 [M+H]+.1H NMR (400 MHz, CD3OD): 7,79-to 7.77 (m, 1H), 7,65-7,63 (m, 1H), 7,45-7,29 (m, 4H), 7.18 in-7,14 (m, 2H), to 4.41 (t,J=4,9, 2H), 3,63 (t,J=4,9, 2H), 3.04 from (s, 6H).

Example 49

2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 12, using the hydrochloride of 1-(2-chloroethyl)pyrrolidine and 2-chlorobenzothiazole. Mass spectrum (ESI): mass calculated for C19H20N2About2S; 340,12; m/z found 341,1 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=7,6, 1H), 7,66 (l,J=8,6, 1H), 7,41 (t,J=7,4, 1H), 7,32-7,25 (m, 3H), 7,00 (l,J=9,0, 2H), 4.16 the (t,J=6,0, 2H), 2,96 (t,J=6,0, 2H), to 2.67 (t,J=6,6, 4H), to 1.86 (quintet,J=3,5, 4H).

Example 50

{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}dimethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 12, using the m hydrochloride (2-chloropropyl)dimethylamine and 2-chlorobenzothiazole. Mass spectrum (ESI): mass calculated for C18H20N2About2S; 328,12; m/z found 329,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), to 7.64 (d,J=7,9, 1H), 7,37 (t,J=to 7.5, 1H), 7,31-7,20 (m, 3H), 6,92 (l,J=7,9, 2H), 4,11 (s, 2H), 3,25 (s, 2H), 2,85 (s, 6H), 2,43 (s, 2H).

Example 51

2-[4-(2-azepin-1 ylethoxy)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 12, using the hydrochloride of 1-(2-chloroethyl)azepane and 2-chlorobenzothiazole. Mass spectrum (ESI): mass calculated for C21H24N2About2S; 368,16; m/z found 369,2 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=to 7.5, 1H), 7,65 (l,J=7,9, 1H), 7,38-7,34 (m, 1H), 7,29-of 7.23 (m, 3H), 6,97 (shirt, 2H), 4,59 (Sirs, 2H), 3,64 (Sirs, 2H), 3.46 in (Sirs, 2H), 3,13 (Sirs, 3H), 2,19 (Sirs, 2H), 1,87 (Sirs, 2H), 1,72 is 1.58 (m, 2H).

Example 52

2-[4-(2-azepin-1 ylethoxy)phenoxy]-6-methoxybenzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 12, using hydrochloride (2-chloroethyl)azepane and 2-chloro-6-methoxybenzothiazole. Mass spectrum (ESI): mass calculated for C2H26N2About3S; 398,17; m/z found 399,2 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.75 (d,J=8,9, 1H), 7,37-7,35 (m, 2H), 7,26 (shirt, 2H), 7,09-7,05 (m, 3H), 4,19 (t,J=6,1, 2H), 3,95(s, 3H), is 3.08 (t,J=6,1, 2H), 2.91 in-2,88 (m, 4H), 1,76 (shirt, 8H).

Example 53

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 13 using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C25H26N2About4; 430,19; m/z found 431,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,60 was 7.45 (m, 3H), 7,40-to 7.18 (m, 8H), 7,00 (l,J=9,1, 2H), 4,18 (t,J=5,9, 2H), 2,92 (t,J=5,9, 2H), 2,66 (dt,J=12,1, 2,4, 2H), 2,22 (dt,J=13,4, 4,5, 2H), 1,80 (DD,J=14,1, 2,4, 2H).

Example 54

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 13, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C23H28N2About3; 380,21; m/z found 381,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=8,4, 1H), 7,42 (l,J=to 7.5, 1H), 7,35-to 7.18 (m, 4H), 6,97 (l,J=9,1, 2H), 3,98 (t,J=6,9, 2H), 2,88 (t,J=6,9, 2H), 2,67 (kV,J=7,1, 2H), 2,55-of 2.50 (m, 1H), 1,82 (t,J=7,4, 4H), 1,64 (l,J=12,4, 1H), 1,21 (t,J=7,9, 4H), of 1.08 (t,J=7,1, 4H).

Example 55

2-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol

Specified in the header connect the Addendum was received in accordance with the methodology described in example 13, using 2-ethylpiperidine. Mass spectrum (ESI): mass calculated for C22H26N2About3; 366,19; m/z found 367,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=7,4, 1H), 7,42 (l,J=7,4, 1H), 7,31 (l,J=9,1, 2H), 7,30-7,20 (m, 2H), 6,97 (l,J=9,1, 2H), 4.09 to (t,J=6,4, 2H), 3.15 and was 3.05 (m, 1H), 3.00 and of 2.92 (m, 1H), 2,88 is 2.80 (m, 1H), 2,48-is 2.37 (m, 1H), 2,30 was 2.25 (m, 1H), 1,75-of 1.65 (m, 4H), 1.60-to and 1.54 (m, 2H), 1,52-of 1.42 (m, 1H), 1,38-1,24 (m, 2H), 0,92 (t,J=7,4, 3H).

Example 56

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-carbonitrile

Specified in the title compound was obtained in accordance with the procedure described in example 13 using 4-phenylpiperidine-4-carbonitrile. Mass spectrum (ESI): mass calculated for C27H25N2About5; 439,19; m/z found 440,2 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.61-7,49 (m, 3H), 7,43-7,38 (m, 3H), of 7.36-7,29 (m, 3H), 7,28-7,20 (m, 3H), 7.03 is-of 6.96 (m, 2H), 4,15 (t,J=5,6, 2H), 3,18 (shirt, 2H), 2,93 (t,J=5,6, 2H), 2.71 to 2,61 (m, 2H), 2,22 is 2.10 (m, 8H).

Example 57

1-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)alanon

Specified in the title compound was obtained in accordance with the procedure described in example 13, using 1-(4-phenylpiperidine-4-yl)ethanone. Mass spectrum (ESI): mass calculated for C28H28N2About4; 456,20; m/z nide what about 457,2 [M+H] +.1H NMR (400 MHz, CDCl3): 7,52-7,49 (m, 1H), 7,43-7,40 (m, 1H), 7,37-7,16 (m, 9H), 6,99-6,92 (m, 2H), 4,10 (t,J=5,8, 2H), 2,87-2,82 (m, 2H), 2,78 (t,J=5,8, 2H), of 2.51-2,47 (m, 2H), 2,39 (shirt, 2H), 2,17-2,05 (m, 2H), 1,92 (s, 3H).

Example 58

2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 13 using 4-methylpiperidine. Mass spectrum (ESI): mass calculated for C21H24N2About3; 352,18; m/z found 353,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50 (d,J=6,8, 1H), 7,42 (l,J=6,8, 1H), 7,31 (l,J=9,0, 2H), 7,30-7,20 (m, 2H), 6,97 (l,J=9,0, 2H), 4,13 (t,J=6,0, 2H), 2,97 (l,J=11,7, 2H), 2,80 (t,J=6,0, 2H), 2,11 (dt,J=11,7,J=2,2,2H), 1,67 (s, 2H), 1,34 (Sirs, 1H), 1.28 (in dt,J=12,2,J=3,4, 2H), were 0.94 (d,J=6,2, 3H).

Example 59

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 13, using 4-(4-chlorophenyl)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H25ClN2About4; 464,15; m/z found 465,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,54-7,42 (m, 4H), 7,37-7,31 (m, 4H), 7,29-7,21 (m, 2H), 7.03 is-6,98 (m, 2H), 4.16 the (t,J=5,8, 2H), 2,93-2,89 (m, 4H), 2,62 (dt,J=12,2, 2,4, 2H), 2.21 are to 2.14 (m, 2H), 1,78-of 1.74 (m, 2H), and 1.56 (Sirs,1H).

Example 60

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 13, using 4-(4-bromophenyl)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H25BrN2About4; 508,10; m/z found 509,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,55-7,47 (m, 3H), 7,44-7,39 (m, 3H), 7,37-7,31 (m, 2H), 7,30-7,19 (m, 2H), 7,02-6,98 (m, 2H), 4,17 (t,J=5,7, 2H), 2,94-2,89 (m, 4H), 2,62 (dt,J=12,2, 2,4, 2H), 2.21 are to 2.13 (m, 2H), 1,78-of 1.74 (m, 2H), and 1.56 (Sirs, 1H).

Example 61

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 13, using 4-(4-chloro-3-triptoreline)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H24ClF3N2About4; 532,14; m/z found 533,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,89 (l,J=2,1, 1H), 7.62mm (DD,J=8,4, 2,1, 1H), 7,51-7,41 (m, 3H), 7,33-7,21 (m, 4H), 6,99-to 6.95 (m, 2H), 4,14 (t,J=5,7, 2H), 2,94-2,89 (m, 4H), 2,65 at 2.59 (m, 2H), 2.21 are to 2.13 (m, 4H), 1,74 (Sirs,1H).

Example 62

1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol

Specified in the title compound was obtained according to the method, described in example 13 using 4-benzylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H28N2About4; 444,20; m/z found 445,1 [M+H]+.1H NMR: (400 MHz, CDCl3) 7,53 is 7.50 (m, 1H), 7,43-7,40 (m, 1H), 7,53-7,21 (m, 10H), 7,01-to 6.95 (m, 2H), 4,12 (t,J=5,9, 2H), 2,84 (t,J=5,8, 2H), 2,78 was 2.76 (m, 4H), 2,47 (dt,J=11,6, 2,4, 2H), 1,83 is 1.75 (m, 2H), 1,59-of 1.53 (m, 2H).

Example 63

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 13, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C22H26N2About3; 366,19; m/z found 367,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.62 (DD,J=6,2,J=2,0, 1H), 7,50 (DD,J=6,1, 2,1, 1H), 7,42 (l,J=9,1, 2H), 7,35-7,25 (m, 2H), 7,03 (l,J=9,1, 2H), Android 4.04 (t,J=6,1, 2H), and 2.79 (t,J=6,1, 2H), 2,45 of-2.32 (m, 1H), 1,73(l,J=7,9, 4H), 1.57 in (q,J=12,2, 2H), 1.30 and of 1.12 (m, 4H), 1,10-1,00 (m, 1H).

Example 64

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 13, using cyclopropanemethylamine. Mass spectrum (ESI): mass calculated for C22H26N2About3; 366,19; m/z found 367,3 [M+H]+ 1H NMR (400 MHz, CDCl3): 7,52 is 7.50 (m, 1H), 7,44-7,41 (m, 1H), 7,33-7,21 (m, 4H), 6,99-to 6.95 (m, 2H), 4.09 to (t,J=6,2, 2H), 3,01 (t,J=6,2, 2H), 2,64 at 2.59 (m, 2H), 2.49 USD (D.,J=J6,3, 2H), 1.60-to 1,50 (m, 2H), 0,92 (t,J=7,3, 4H), 0.55 to 0.52 in (m, 2H), 0,16-0,13 (m, 2H).

Example 65

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}butylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 13, using butylethylamine. Mass spectrum (ESI): mass calculated for C21H26N2About3; 354,19; m/z found 355,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,41 (l,J=7,2, 1H), 7,32 (DD,J=7,3, 1,6, 1H), 7,22 (l,J=9,1, 1H), 7.18 in-7,10 (m, 2H), 6.87 in (q,J=9,1, 2H), was 4.02 (Sirs, 2H), 2,85 (Sirs, 2H), 2,61 (Sirs, 2H), 2.49 USD (Sirs, 2H), 1,42 (Sirs, 2H), 1,31-1,19 (m, 2H), 1,05 (Sirs, 3H), or 0.83 (t,J=7,3, 3H).

Example 66

2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}benzylamino)ethanol

Specified in the title compound was obtained in accordance with the procedure described in example 13, using benzylaminopurine. Mass spectrum (ESI): mass calculated for C24H24N2About4; 404,17; m/z found 405,2 [M+H]+.1H NMR (400 MHz, CD3OD): 7,46-7,37(m, 3H), 7,33 (l,J=16,9, 2H), 7,29-7,00 (m, 6H), to 6.95 (d,J=6,9, 2H), 4,06 (t,J=5,8, 2H), 3,76 (s, 2H), 3,64 (t,J=6,2, 2H), 2.95 and (l,J=5,8, 2H), was 2.76 (t,J=6,1, 2H).

Example 67

2-{4-[2-(4-benzylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 13 using 4-benzylpiperidine. Mass spectrum (ESI): mass calculated for C27H28N2About3; 428,21; m/z found 429,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,53 is 7.50 (m, 1H), 7,44-7,41 (m, 1H), 7,33-to 7.15 (m, 9H), 6,98-to 6.95 (m, 2H), 4,11 (t,J=6,0, 2H), 3,01-2,96 (m, 2H), and 2.79 (t,J=6,0, 2H), 2,55 (l,J=7,0, 2H), 2,09-2,02 (m, 2H), 1,67-of 1.64 (m, 2H), 1,59-is 1.51 (m, 1H) 1,40-of 1.29 (m, 2H).

Example 68

(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol

Specified in the title compound was obtained in accordance with the procedure described in example 13, using piperidine-3-ylmethanol. Mass spectrum (ESI): mass calculated for C21H24N2About4; 368,17; m/z found 369,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,55-7,52 (m, 1H), of 7.48-7,44 (m, 1H), 7,38-of 7.23 (m, 4H), 7,05-of 6.99 (m, 2H), 4,23 (t,J=5,6, 2H), 3,71 (DD,J=10,7, 5,1, 1H)and 3.59 (DD,J=10,6, 6,4, 1H), 3,09 (shirt,J=9,7, 1H), 2,94 (t,J=5,6, 2H), 2,42 (t,J=9,1, 1H), 2,29 (t,J=9,3, 1H), 2,24-to 1.98 (m, 2H), 2.00 in 1,90 (m, 1H), 1,90 and 1.80 (m, 1H), 1,80-1,71 (m, 2H), 1,20-1,10 (m, 1H).

Example 69

2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}propylamino)ethanol

Specified in the title compound was obtained in accordance with the method described in example 13, using 2-propylaminoethyl. Mass spectrum (ESI): mass calculated for C20H24N2About4; 356,17; m/z found 357,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.62 (DD,J=6,2, 2,0, 1H), 7,50 (DD,J=6,1, 2,1, 1H), 7,42 (l,J=9,1, 2H), 7,35-7,25 (m, 2H), 7,03 (l,J=9,1, 2H), or 4.31 (t,J=5,4, 1H), Android 4.04 (t,J=6,0, 2H), 3.46 in (kV,J=6,4, 2H), 2,85 (t,J=6,0, 2H), 2,59 (t,J=6,5, 2H), of 2.51-2,48 (m, 2H), 1,41 (kV,J=7,4, 2H), 0,84 (t,J=7,3, 3H).

Example 70

1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-phenylphenanthridine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 17 using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H26N2About3S; 446,17; m/z found 447,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,1, 1H), 7,66 (l,J=7,4, 1H), 7,54 (e,J=7,6, 2H), 7,42-7,35 (m, 3H), 7,33-7,22 (m, 4H), 6,99 (l,J=9,0, 2H), 4,19 (t,J=5,8, 2H), 2,98-of 2.86 (m, 4H), 2,65 (dt,J=13,8, 2,1, 2H), 2,24 (dt,J=13,4, 4,5, 2H), 1,80 (DD,J=14,1, 2,2, 2H).

Example 71

{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 17, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C23H28N2About2 S; 396,19; m/z found 397,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,1, 1H), 7,65 (l,J=7,9, 1H), 7,39 (t,J=7,9, 4H), 7,30-7,20 (m, 4H), of 6.96 (d,J=8,9, 2H), 3,98 (t,J=6,8, 2H), 2,89 (t,J=6,8, 2H), 2,66 (kV,J=7,1, 2H), 2,55-of 2.50 (m, 1H), 1,82 (t,J=7,7, 4H), 1,65 (l,J=11,9, 1H), 1.30 and of 1.18 (m, 4H), of 1.09 (t,J=7,2, 4H).

Example 72

1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 17 using 4-(4-chlorophenyl)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H25ClN3About3S; 480,13; m/z found 481,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=7,6, 1H), 7,66 (DD,J=7,9, 0,8, 1H), 7,49 was 7.45 (m, 2H), 7,41-7,22 (m, 6H), 7,01-6,97 (m, 2H), 4,18 (t,J=5,8, 2H), 2,96-2,89 (m, 4H), 2.63 in (dt,J=12,1, 2,4, 2H), 2.21 are to 2.14 (m, 2H), 1,79-of 1.74 (m, 2H), and 1.56 (Sirs, 1H).

Example 73

{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dibutylamine

Specified in the title compound was obtained in accordance with the procedure described in example 17, using dibutylamine. Mass spectrum (ESI): mass calculated for C23H30N2About2S; 398,20; m/z found 399,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,63 (l,J=8,1, 1H), 7,55 (l,J=7,9, 1H), 7,28 (TT,J=7,7, 1,3, 1H), 7,20-7,13 (m, 3H), 6,85 (l,J=12,8, 2H), 3.96 points (t,J=5,6, 2H), 2,80 (m, 2H, 2,43 (m, 4H), to 1.38 (m, 4H), 1,22 (m, 4H), or 0.83 (t,J=7,3 Hz, 6H).

Example 74

1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 17 using 4-(4-bromophenyl)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H25BrN2About3S; 524,08; m/z found 525,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (DD,J=8,0, 0,6, 1H), to 7.67 (DD,J=8,0, 0,8, 1H), 7,53-7,47 (m, 2H), 7,43-7,37 (m, 3H), 7,30-7,22 (m, 3H), 7,01-6,98 (m, 2H), 4,17 (t,J=5,8, 2H), 2,94-2,89 (m, 4H), 2.63 in (dt,J=12,1, 2,5, 2H), 2.21 are to 2.14 (m, 2H), 1,76 (DD,J=14,2, 2,6, 2H), and 1.56 (Sirs, 1H).

Example 75

1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 17 using 4-(4-chloro-3-triptoreline)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H24ClF3N2About3S; 548,11; m/z found 549,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,89 (l,J=2,1, 1H), 7,62-of 7.48 (m, 4H), 7,41-7,37 (m, 1H), 7,30-7,24 (m, 3H), 7,01-6,97 (m, 2H), 4,17 (t,J=5,8, 2H), 2,94-only 2.91 (m, 6H), 2,66 at 2.59 (m, 2H), 2,22-of 2.15 (m, 2H), 1,83 (Sirs, 1H).

Example 76

1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-benzyl is peridin-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 17 using 4-benzylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H28N2About3S; 460,18; m/z found 461,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), 7,66 (l,J=7,7, 1H), 7,41-of 7.23 (m, 9H), 6,99-6,94 (m, 2H), 4,13 (t,J=5,9, 2H), 4,84 (t,J=5,9, 2H), 2,78 (m, 4H), 2,50 at 2.45 (m, 2H), 1,83 to 1.76 (m, 2H), 1,59-of 1.52 (m, 2H), 1,23 (Sirs, 1H).

Example 77

2-[4-(2-azetidin-1 ylethoxy)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 21, using azetidine. Mass spectrum (ESI): mass calculated for C18H18N2About3; 310,13; m/z found 311,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.61 (d,J=7,0, 2H), of 7.48 (d,J=7,0, 2H), 7,41 (l,J=9,1, 2H), 7,32-7,24 (m, 2H), 7,00 (l,J=6,9, 2H), 3,93 (t,J=5,6, 2H), 3,18 (t,J=6,9, 4H), 2,70 (t,J=5,6, 2H), 1.97 of (t,J=6,9, 2H).

Example 78

N-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide

Specified in the title compound was obtained in accordance with the procedure described in example 22 using 2-phenyl-N-piperidine-4-ylacetamide and 2-chlorobenzoxazole. Mass spectrum (ESI): mass calculated for C28H29N3the 4; 471,22; m/z found 472,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,55-7,51 (m, 1H), 7,47-the 7.43 (m, 1H), 7,41-of 7.23 (m, 9H), 7,00-to 6.95 (m, 2H), 5,28 (shirt,J=7,8, 1H), 4,10 (t,J=5,7, 2H), 3,90-of 3.80 (m, 1H), 3,60 (s, 2H), 2,89 (shirt,J=11,5, 2H), 2,81 (t,J=5,8, 2H), 2,28 (dt,J=11,6, 2,2, 2H), 1,92 (sird,J=12,6, 2,3, 2H), 1,46 to 1.37 (m, 2H).

Example 79

Ethyl ester of 1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 22, using ethyl ether piperidine-3-carboxylic acid and 2-chlorobenzoxazole. Mass spectrum (ESI): mass calculated for C23H26N2About5; 410,18; m/z found 411,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,56-7,52 (m, 1H), 7,47-the 7.43 (m, 1H), 7,37-to 7.32 (m, 2H), 7,32-of 7.23 (m, 2H), 7,02-6,98 (m, 2H), 4,18 (kV,J=7,1, 2H), 4,15 (t,J=5,9, 2H), 3,14 (shirt,J=8,2, 1H), 2,96-2,82 (m, 3H), 2,65 (TT,J=10,6, 3,7, 1H), 2,37 (t,J=10,7, 1H), measuring 2.20 (dt,J=10,9, 2,7, 1H), 2,03-of 1.97 (m, 1H), 1,82 is 1.75 (m, 1H), 1,73 is 1.60 (m, 1H), 1,54-of 1.45 (m, 1H) 1,30 (t,J=7,2, 3H).

Example 80

1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipiperidine

Specified in the title compound was obtained in accordance with the procedure described in example 22 using 4-piperidinylidene. Mass spectrum (ESI): mass calculated for C25H31N3About2S; 437,21; m/z is ideno 438,4 [M+H] +.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=8,0, 1H), 7,69 (l,J=7,0, 1H), 7,42 (dt,J=7,1, 1,1, 1H), 7,35-7,26 (m, 3H),? 7.04 baby mortality-6,97 (m, 2H), 4,15 (t,J=5,9, 2H), 3,11 (shirt,J=11,7, 2H), 2,84 (t,J=6,0, 2H), 2.57 m (Sirs, 2H), 2.40 a-2,30 (m, 1H), 2,16 (dt,J=11,7, 1,6, 1H), 1,85 (shirt,J=12,1, 2H), 1,75-to 1.59 (m, 8H), 1,52-of 1.40 (m, 2H).

Example 81

(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol

Specified in the title compound was obtained in accordance with the procedure described in example 17, using piperidinyl-4-ylmethanol. Mass spectrum (ESI): mass calculated for C21H24N2About3S; 384,15; m/z found 385,1 [M+H]+.1H NMR (500 MHz, CDCl3): 7,75-7,73 (m, 1H), to 7.67-the 7.65 (m, 1H), 7,41-7,37 (m, 1H), 7,31 and 7.36 (m, 3H), 6,98-to 6.95 (m, 2H), 4,13 (t,J=5,9, 2H), 3,52 (t,J=5,4, 2H), 3,10-3,03 (m, 2H), and 2.83 (t,J=5,9, 2H), and 2.14 (dt,J=11,8, 2,4, 2H), 1,78 is 1.75 (m, 2H), 1,58-of 1.52 (m, 2H), 1,37-of 1.30 (m, 2H).

Example 82

N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide

Specified in the title compound was obtained in accordance with the procedure described in example 22 using 2-phenyl-N-piperidine-4-ylacetamide. Mass spectrum (ESI): mass calculated for C28H29N3About3S; 487,19; m/z found 488,2 [M+H]+.1H NMR (400 MHz, CDCl3): for 7.78 (DD,J=8,0, 0,6, 1H), 7,69 (DD,J=7,9, 0,7, 1H), 7,45-7,24 (m, 9H), 7,00-to 6.88 (m, 2H), 5,33 (is, J=7,9, 1H), 4,10 (t,J=5,8, 2H), 3,90-with 3.79 (m, 1H), 3,60 (s, 2H), 2,88 (l,J=11,7, 2H), 2,80 (t,J=5,7, 2H), and 2.27 (dt,J=11,6, 2,2, 2H), 1,92 (DD,J=12,7, 3,6, 2H), 1.39 in (DKV,J=11,1, 3,8, 2H).

Example 83

1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 22, using [1,4']bipyridinyl-2-it. Mass spectrum (ESI): mass calculated for C25H29N3About3S; 451,59; m/z found 452,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): to $ 7.91 (d,J=7,4, 1H), to 7.67 (d,J=7,4, 1H), 7,45-to 7.32 (m, 4H), 7,06 (l,J=9,0, 2H), 4,35-to 4.15 (m, 1H), 4,10 (t,J=5,7, 2H), 3.15 in (t,J=5,3, 2H), 3.00 and (l,J=11,5, 2H), 2,71 (t,J=5,7, 2H), 2,21 (t,J=6,5, 2H), 2,10 (t,J=11,5, 2H), 1,75-to 1.60 (m, 6H), 1,43 (l,J=10,0, 2H).

Example 84

2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethoxy}phenoxy)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 22 using 4-(2-piperazine-1-retil)of the research. Mass spectrum (ESI): mass calculated for C25H32N4About3S; 468,22; m/z found 469,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): to $ 7.91 (d,J=7,9, 1H), to 7.67 (d,J=7,9, 1H), 7,45-to 7.32 (m, 4H), 7,06 (l,J=9,1, 2H), 4.09 to (t,J=5,8, 2H), 3,54 (t,J=4,6, 2H), 2,68 (t,J=5,7, 2H), 2,50-2,20 (Sirs, 16H).

Por the measures 85

2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethyl}phenoxy)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 32 using 4-(2-piperazine-1-retil)of the research. Mass spectrum (ESI): mass calculated for C25H32N4About2S; 452,22; m/z found 453,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=8,0, 1H), 7.68 per (e,J=8,0, 1H), 7,45-7,30 (m, 6H), 3,54 (t,J=4,5, 4H), 2,75 (t,J=8,3, 4H), 2,50-2,20 (Sirs, 16H).

Example 86

2-{4-[3-(4-phenylpiperazin-1-yl)propoxy]phenoxy}benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 27 using 4-phenylpiperidine. Mass spectrum (ESI): mass calculated for C27H28N2About3; 428,21; m/z found 429,2 [M+H]+.1H NMR (400 MHz, CD3OD): 7,40-7,38 (m, 1H), 7,34-7,32 (m, 1H), 7,24 (l,J=9,1, 2H), 7,22 for 7.12 (m, 4H), 7,07 (t,J=7,0, 1H), 6,94 (l,J=9,1, 2H), 3,99 (t,J=6,1, 2H), 3,06 (l,J=11,7, 2H), 2.57 m (t,J=7,6, 2H), 2.49 USD (m, 1H), 2.13 in (t,J=11,6, 2H), of 1.97(m, 2H), 1,73 (m, 4H).

Example 87

1-{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 27 using 2-chlorobenz is thiazole. Mass spectrum (ESI): mass calculated for C27H28N2About3S; 460,18; m/z found 461,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,65 (l,J=7,8, 1H), 7,53 (l,J=8,2, 2H), 7,39-7,35 (m, 3H), 7,29-of 7.23 (m, 5H), of 6.96 (d,J=9,1, 2H), 4,08 (t,J=6,2, 2H), 2,92 (m, 2H), 2,72-2,49 (m, 4H), 2,34-2,02 (m, 4H), 1,81 (l,J=12,3, 2H).

Example 88

1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 29 using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H28N2About3; 414,51; m/z found 415,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,56-7,51 (m, 3H), 7,45-to 7.32 (m, 6H), 7,30-7,22 (m, 4H), 2,96-2,89 (m, 2H), 2,74-2,69 (m, 2H), 2,61-of 2.54 (m, 2H), 2.26 and-to 2.18 (m, 2H), 1,84-to 1.79 (m, 2H), 1,62 (Sirs, 1H).

Example 89

{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 29, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C23H28N2About2; 364,22; m/z found 365,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=7,8, 1H), 7,41 (l,J=7,6, 1H), 7,33-to 7.18 (m, 6H), 2,80 of 2.68 (m, 4H), of 2.64 (DD,J=6,8,? 7.04 baby mortality, 2H), 2,58-of 2.50 (m, 1H), 1,80 (t,J=8,8, 4H), and 1.63 (d,J=12,3, 1H), 1,22 (DD,J =9,8, 8,4, 4H), of 1.08 (t,J=7,0, 4H).

Example 90

2-[4-(2-pyrrolidin-1-retil)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 29, using pyrrolidine. Mass spectrum (ESI): mass calculated for C19H20N2About2; 308,15; m/z found 309,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=7,6, 1H), 7,42 (l,J=7,2, 1H), 7,35-7,20 (m, 6H), 2,90-2,84 (m, 2H), 2,75 of 2.68 (m, 2H), 2,62 is 2.55 (m, 4H), 1.85 to to 1.79 (m, 4H).

Example 91

2-[4-(2-azepin-1-retil)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 29, using azepane. Mass spectrum (ESI): mass calculated for C21H24N2About2; 336,18; m/z found sauce 337,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50 (d,J=7,6, 1H), 7,39 (l,J=7,8, 1H), 7,33-7,17 (m, 6H), 2,84-by 2.73 (m, 4H), 2,71 (t,J=5,3, 4H), 1,71-of 1.57 (m, 8H).

Example 92

{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 29, using cyclopropanemethylamine. Mass spectrum (ESI): mass calculated for C22H26N2About2; 350,20; m/z found 351,1 [M+H] +.1H NMR (400 MHz, CDCl3): 7,50 (d,J=7,6, 1H), 7,39 (l,J=7,8, 1H), 7,33-7,17 (m, 6H), 2,85-to 2.74 (m, 4H), of 2.56 (t,J=7,6, 2H), 2,43 (l,J=6,5, 2H), 1.56 to the 1.44 (m, 2H), 0,90 (t,J=7,2, 4H), 0,51 (DD,J=7,8, and 5.5, 2H), 0,13 (DD,J=7,8, and 5.5, 2H).

Example 93

{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}dibutylamine

Specified in the title compound was obtained in accordance with the procedure described in example 29, using dibutylamine. Mass spectrum (ESI): mass calculated for C23H30N2About2; 366,23; m/z found 367,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=7,4, 1H), 7,39 (l,J=7,6, 1H), 7,33-7,17 (m, 6H), 2,80-of 2.66 (m, 4H), 2.49 USD (t,J=7,3, 4H), 1,50-of 1.40 (m, 4H), 1,37-of 1.26 (m, 4H), of 0.93 (t,J=7,2, 6H).

Example 94

1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 29 using 4-hydroxypiperidine. Mass spectrum (ESI): mass calculated for C20H22N2About3; 338,16; m/z found 339,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50 (d,J=7,6, 1H), 7,39 (l,J=7,6, 1H), 7,34-7,16 (m, 6H), 3.72 points-3,63 (m, 1H), 3,29 (Sirs, 1H), 2.91 in-2,78 (m, 4H), 2,63-of 2.56 (m, 2H), 2,21 (t,J=10,0, 2H), 1,96 is 1.86 (m, 2H), 1.70 to of 1.57 (m, 2H).

Example 95

1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-about the

Specified in the title compound was obtained in accordance with the procedure described in example 30, using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H26N2About3S; 430,57; m/z found 431,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76-7,74 (m, 1H), to 7.67 (DD,J=8,0, 0,7, 1H), 7,56-7,53 (m, 2H), 7,42 and 7.36 (m, 3H), 7,33-7,26 (m, 6H), 2,96-of 2.86 (m, 4H), 2,75-7,71 (m, 2H), 2,64-of 2.56 (m, 2H) 2,27-to 2.18 (m, 2H), 1,86 and 1.80 (m, 2H), 1,67-1,66 (SIRM, 2H).

Example 96

Methyl ester 1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 29, using methyl ether piperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C22H24N2About4; 380,17; m/z found 381,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,50 (d,J=8,1, 1H), 7,39 (l,J=8,1, 1H), 7,34-7,16 (m, 6H), to 3.67 (s, 3H), 2,97-2,90 (m, 2H), 2,84-2,78 (m, 2H), 2,60-to 2.55 (m, 2H), 2,35 was 2.25 (m, 1H), 2,10 (t,J=11,4, 2H), 1,96-of 1.88 (m, 2H), 1,84-of 1.73 (m, 2H).

Example 97

2-[4-(2-pyrrolidin-1-retil)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 30, using pyrrolidine. Mass spectrum (ESI): mass calculated for C19H20N2OS; 324,13; m/z found the 325,3 [M+H] +.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,65 (l,J=8,0, 1H), 7,38 (t,J=7,2, 1H), 7,31-7,22 (m, 5H), 2.91 in-and 2.83 (m, 2H), 2.77-to 2,69 (m, 2H), 2,64 is 2.55 (m, 4H), to 1.87-1.77 in (m, 4H).

Example 98

2-[4-(2-azepin-1-retil)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 30, using azepane. Mass spectrum (ESI): mass calculated for C21H24N2OS; 352,16; m/z found 353,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,65 (l,J=8,0, 1H), 7,37 (t,J=7,4, 1H), 7,30-7,22 (m, 5H), 2,87-2,70 (m, 8H), 1,73-of 1.57 (m, 8H).

Example 99

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 30, using cyclopropanemethylamine. Mass spectrum (ESI): mass calculated for C22H26N2OS; 366,18; m/z found 367,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,6, 1H), 7,65 (l,J=8,2, 1H), 7,38 (t,J=8,6, 1H), 7,30-7,22 (m, 5H), 2,87 was 2.76 (m, 4H), 2.57 m (t,J=7,6, 2H), 2,44 (l,J=6,5, 2H), 1.56 to a 1.45 (m, 2H), 0,90 (t,J=7,4, 4H), 0,52 (DD,J=7,8, and 5.5, 2H), 0,14 (DD,J=5,7, 5,1, 2H).

Example 100

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}dibutylamine

Specified in the title compound floor is Ali in accordance with the methodology described in example 30, using dibutylamine. Mass spectrum (ESI): mass calculated for C3H30N2OS; 382,21; m/z found 383,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,2, 1H), 7,65 (l,J=8,2, 1H), 7,38 (t,J=8,2, 1H), 7,30-7,22 (m, 5H), 2,82-to 2.67 (m, 4H), of 2.51 (t,J=7,2, 4H), 1,50-of 1.40 (m, 4H), 1,37-1,25 (m, 4H), of 0.93 (t,J=7,2, 6H).

Example 101

2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 30, using piperidine. Mass spectrum (ESI): mass calculated for C20H22N2OS; 338,48; m/z found 339,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,76-7,73 (m, 1H), of 7.64-to 7.61 (m, 1H), 7,42-7,25 (m, 6H), 2,88-and 2.83 (m, 2H), 2,60-2,52 (m, 6H), 1,66-to 1.61 (m, 4H), 1,53-of 1.45 (m, 2H).

Example 102

1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 30, using 4-hydroxypiperidine. Mass spectrum (ESI): mass calculated for C20H22N2About2S; 354,14; m/z found 355,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,2, 1H), to 7.64 (d,J=8,0, 1H), 7,37 (t,J=8,2, 1H), 7,29-7,20 (m, 5H), 3.75 to the 3.65 (m, 1H), 2,92-and 2.79 (m, 4H), was 2.76 (Sirs, 1H), 2,65 is 2.55 (m, 2H), 2,21 (t,J=10,0, 2H), 1,98-to 1.87 (m, 2H), 1.70 to of 1.57 (m, 2H).

Example 103

Methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 30, using methyl ether piperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C22H24N2About2S; 396,15; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,3, 1H), 7,66 (l,J=8,3, 1H), 7,38 (t,J=8,3, 1H), 7,29-of 7.23 (m, 5H), 3,69(with,3H), 3.00 and-of 2.93 (m, 2H), 2,87 is 2.80 (m, 2H), 2,63-of 2.56 (m, 2H), 2,38-of 2.28 (m, 1H), 2,11 (t,J=11,1, 2H), 1,98 is 1.91 (m, 2H), 1,86-of 1.74 (m, 2H).

Example 104

Amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 31, using amide piperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C21H23N3About2S; 381,15; m/z found 382,3 [M+H]+.1H NMR (400 MHz, CDCl3): for 7.78 (DD,J=8,1, 0,4, 1H), 7,71 (DD,J=7,9, 0,7, 1H), 7,43 (dt,J=7,5, 2,3, 1H), 7,35-7,25 (m, 5H), 5,51 (shirt,J=26,0, 1H), 3,09 (shirt,J=11,7, 2H), 2,87, (DD,J=8,3, 7,6, 2H), 2,65 (DD,J=8,5, 5,4, 2H), 2,29-to 2.18 (m, 1H), 2.13 in (t,J=11,4, 2H), 1,98 (shirt,J=11,2, 2H), 1,87-to 1.77 (m, 2H).

Example 105

Ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperid the h-3-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 31, using ethyl ether piperidine-3-carboxylic acid. Mass spectrum (ESI): mass calculated for C23H26N3About2S; 410,17; m/z found 411,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=8,0, 1H), of 7.70 (DD,J=7,9, 0,5, 1H), 7,42 (dt,J=7,5, 1,3, 1H), 7,34-7,27 (m, 5H), 4,18 (kV,J=7,1, 2H), 3,13 (shirt,J=8,8, 1H), 2,92-to 2.85 (m, 2H), 2,70 at 2.59 (m, 2H), 2,30 (t,J=10,7, 1H), 2,13 (dt,J=10,9, 2,7, 1H), 2,04-of 1.97 (m, 1H), 1,84 to 1.76 (m, 1H), 1,71-to 1.59 (m, 1H), 1,57-of 1.45 (m, 1H) 1,30 (t,J=7,2, 3H).

Example 106

Ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 31, using the ethyl ester of 4-phenylpiperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C29H30N3About2S; 486,20; m/z found 487,5 [M+H]+.1H NMR (400 MHz, CDCl3): for 7.78 (DD,J=8,1, 0,5, 1H), of 7.70 (DD,J=7,9, 0,7, 1H), 7,46-7,24 (m, 11H), 4,19 (kV,J=7,1, 2H), 3,06 (shirt,J=10,1, 2H), 2,96-2,90 (m, 2H), 2,75-of 2.64 (m, 4H), 2,35 (t,J=11,0, 2H), 2,14, (t,J=11,3, 2H), 1,24, (t,J=7,3, 3H).

Example 107

Ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid

Listed is in the title compound was obtained in accordance with the methodology described in example 31, using ethyl ether piperidine-4-luxusni acid. Mass spectrum (ESI): mass calculated for C24H28N3About3S; 424,18; m/z found 425,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=7,8, 1H), of 7.70 (DD,J=7,9, 0,6, 1H), 7,41 (dt,J=7,2, 1,2, 1H), was 7.36-7,27 (m, 5H), 4,18 (kV,J=5,3, 2H), 3,21 (l,J=11,3, 2H), 3,03-2,99, (m, 2H), 2,83-2,78 (m, 2H), 2,33 was 2.25 (m, 4H), 2.00 in to 1.87 (m, 1H), 1,86 (l,J=14,3, 2H), 1,67-of 1.55 (m, 2H), 1,29 (t,J=7,1, 3H).

Example 108

1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dihydroindol-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 31 using 1-piperidine-4-yl-1,3-dihydroindol-2-it. Mass spectrum (ESI): mass calculated for C28H27N3About2S; 469,18; m/z found 470,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.75 (DD,J=8,1, 0,4, 1H), 7,68 (DD,J=7,9, 0,6, 1H), 7,40 (dt,J=7,5, 1,2, 1H), was 7.36-7.23 percent (m, 8H),? 7.04 baby mortality (dt,J=7,3, 1,7, 1H), 4,57 is 4.45 (m, 1H), 3,54 (s, 2H), 3,36 (shirt,J=10,9, 2H), 3,00 (DD,J=11,4, 6,3, 1H), 2,88 (DD,J=8,8, 4,5, 2H), 2,75-2,62 (m, 2H), 2,45 (t,J=11,5, 2H), 1,80 (DD,J=12,3, 2,1, 2H).

Example 109

1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 31, with ispolzovaniem-piperidine-4-iparralde-2-it. Mass spectrum (ESI): mass calculated for C24H27N3About2S; 421,18; m/z found 422,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=8,0, 1H), 7,69 (DD,J=8,0, 0,9, 1H), 7,41 (dt,J=7,5, 1,2, 1H), 7,32-7,27 (m, 5H), of 4.05 (dt,J=11,9, and 4.5, 1H), 3,40 (t,J=7,0, 2H), 3,10 (shirt,J=11,7, 2H), 2,86 (DD,J=11,0, 7,7, 2H), 2,66 (DD,J=8,8, 5,3, 2H), 2,43 (t,J=8,1, 2H), 2,19 (dt,J=11,6, 2,8, 2H), 2,09 is 2.00 (m, 2H), 1.85 to 1.69 in (m, 4H).

Example 110

N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-2-phenylacetamide

Specified in the title compound was obtained in accordance with the procedure described in example 31 using 2-phenyl-N-piperidine-4-ylacetamide. Mass spectrum (ESI): mass calculated for C28H29N3About2S; 471,20; m/z found 472,5 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DDJ=8,1, 0,5, 1H), of 7.70 (DD,J=7,8, 0,7, 1H), 7,45-7,37 (m, 3H), of 7.36-7,26 (m, 8H), 5,39 (shirt,J=7,9, 1H), 3,93-3,82 (m, 1H), 3,60 (s, 2H), 2,93 (shirt,J=11,1, 2H), 2,86 (DD,J=10,9, 7,6, 2H), 2,65 (DD,J=8,5, 5,2, 2H, in), 2.25 (t,J=11,2, 2H), 1,95 (DD,J=12,8, 3,3, 2H), 1,47 (m, 2H).

Example 111

8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-2,8-diaza-Spiro[4.5]Decan-1-he

Specified in the title compound was obtained in accordance with the procedure described in example 31, using 2,8-diaza-Spiro[4.5]Decan-1-it. Mass spectrum (ESI): mass calculated for C23sub> 25N3About2S; 407,17; m/z found 408,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,78 (l,J=8,1, 1H), of 7.70 (DD,J=7,8, 0,6, 1H), 7,42 (dt,J=7,6, 1,3, 1H), 7,35-7,25 (m, 5H), 6,40 (Sirs, 1H), 3,40 (t,J=6,9, 2H), 3.00 and (dt,J=11,6, 3,6, 2H), 2,88 (DD,J=10,3, 7,4, 2H), to 2.67 (DD,J=8,5, 5,7, 2H), 2,23 (t,J=10,7, 2H), 2,10-2,00 (m, 4H), 1,52 (shirt,J=13,1, 2H).

Example 112

1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-ol

Specified in the title compound was obtained in accordance with the procedure described in example 31 using 3-hydroxypiperidine. Mass spectrum (ESI): mass calculated for C20H22N2About2S; 354,14; m/z found 355,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=7,6, 1H), of 7.70 (DD,J=8,0, 0,8, 1H), 7,42 (dt,J=7,5, 1,2, 1H), 7,35-7,28 (m, 5H), to 3.89 (m, 1H), 2,89 (DD,J=10,1, 7,3, 2H), 2.71 to to 2.65 (m, 2H), 2,64-of 2.54 (m, 2H), 2,53-of 2.36 (m, 3H), 1,92 and 1.80 (m, 1H), 1,74-of 1.55 (m, 3H).

Example 113

Ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 31, using ethyl ether piperidine-3-carboxylic acid. Mass spectrum (ESI): mass calculated for C23H26N2About3S; 410,17; m/z found 411,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=8,0, 1H), 7,69 (DD,J=7,9, ,7, 1H), 7,41 (dt,J=7,5, 1,2, 1H), 7,32-7,27 (m, 5H), 4,18 (kV,J=7,1, 2H), 3.00 and (shirt,J=11,5, 2H), 2,88 (DD,J=10,9, 7,7, 2H), 2,64 (DD,J=8,5, 5,3, 2H), 2,35 (TT,J=10,9, 4,3, 1H), 2,14, (t,J=10,9, 2H), 2,02-of 1.94 (m, 2H), 1,90-of 1.78 (m, 2H), 1,30 (t,J=7,3, 3H).

Example 114

1'-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-[1,4']bipiperidine

Specified in the title compound was obtained in accordance with the procedure described in example 31 using 4-piperidinylidene. Mass spectrum (ESI): mass calculated for C25H31N3OS; 421,22; m/z found 422,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.75 (d,J=7,8, 1H), 7,69 (DD,J=7,8, 0,6, 1H), 7,41 (dt,J=7,6, 1,2, 1H), 7,33-7,25 (m, 5H), 3.15 in (shirt,J=11,6, 2H), 2,90-2,70 (m, 7H) to 2.65 (DD,J=8,5, 5,3, 2H), 2,18-to 2.06 (m, 4H), 1,99-to 1.87 (m, 4H), 1.85 to about 1.75 (m, 2H), 1,64-of 1.56 (m, 2H).

Example 115

2-{4-[2-(4-methylpiperazin-1-yl]ethyl}phenoxy)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 32, using 1-methylpiperazine. Mass spectrum (ESI): mass calculated for C20H23N3OS; 353,16; m/z found 354,1 [M+H]+.1H NMR (400 MHz, CD3OD): to 7.77 (d,J=8,01, 1H), to 7.64 (d,J=8,1, 1H), 7,41 (t,J=8,2, 1H), 7,37 (l,J=8,6, 2H), 7,32-7,28 (m, 3H), 2,81 to 2.35 (m, 8H), 2,87 (m, 2H), 2,65 (m, 2H), 2,30 (s, 3H).

Example 116

1-{3-[4-(benzooxazol the l-2-yloxy)phenyl]propyl}-4-phenylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 35 using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H28N2About3; 428,21; m/z found 429,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.48 (d,J=8,4, 1H), 7,45 (m, 11H), 7,19 (t,J=8,3, 1H), amounts to 4.76 (s, 1H), 2,66 (t,J=7,6, 4H), of 2.45 (m,4H), 1,92 (t,J=7,1, 2H), 1,78 (t,J=7,1, 2H), 1,58 (l,J=12,3, 2H).

Example 117

1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 37 using 4-(4-bromophenyl)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H26BrN3About3; 507,12; m/z found 508,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,43-7,07 (m, 10H), 6,94-6,89 (m, 2H), 4,11 (t,J=5,8, 2H), 2,87-and 2.83 (m, 4H), 2,65-of 2.58 (m, 2H), 2,13-2,05 (m, 2H), 1,75 by 1.68 (m, 2H).

Example 118

1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 37 using 4-(4-chlorophenyl)piperidine-4-ol. Mass spectrum (ESI): mass calculated for C26H28ClN3About3; 463,17; m/z found 464,2 [M+H]+.1H NMR (400 MG IS, CDCl3): 7,38-7,22 (m, 6H), 7,17 for 7.12 (m, 2H), 7,09? 7.04 baby mortality (m, 2H), 6,91-for 6.81 (m, 2H), 4,08 (t,J=5,6, 2H), 2,84 is 2.80 (m, 4H), 2,62 (t,J=11,8, 2H), 2,09-2,02 (m, 2H), 1.70 to of 1.65 (m, 2H).

Example 119

1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 37 using 4-benzylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H29N3About3; 443,22; m/z found 444,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,53 (Sirs, 1H), 7,34-7,24 (m, 4H), 7,26-7,16 (m, 7H), 6,91-6,85 (m, 2H), 4,08 (t,J=5,8, 2H), 2,85-2,77 (m, 6H), 2,48 (dt,J=2,5, 11,7, 2H), 1,84 to 1.76 (m, 2H), and 1.56 (m, 2H).

Example 120

2-[4-(3-piperidine-1-ylpropyl)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 35, using piperidine. Mass spectrum (ESI): mass calculated for C21H24N2About2; 336,18; m/z found 337,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.62 (DD,J=5,7,2,1, 1H), 7,50 (DD,J=6,1, 2,1, 1H), 7,45-7,35 (m, 2H), 7,35-7,25 (m, 4H), 2,62 (t,J=7,6, 2H), 2,30 (s, 4H), of 2.25 (t,J=7,4, 2H), 1,80 is 1.70 (m, 2H), 1,55-of 1.45 (m, 4H), of 1.42 and 1.35 (m, 2H).

Example 121

{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}dibutylamine

Specified in the header connect the Addendum was received in accordance with the methodology described in example 35, using dibutylamine. Mass spectrum (ESI): mass calculated for C24H32N2About2; 380,25; m/z found 381,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,63 (DD,J=6,1, 2,1, 1H), 7,50 (DD,J=6,1, 2,1, 1H), 7,40 (l,J=8,6, 2H), 2.63 in (t,J=7,7, 2H), 2,50-of 2.30 (m, 6H), to 1.70 (quintet,J=7,2, 2H), 1,40-of 1.20 (m, 8H), to 0.88 (t,J=7,1, 6H).

Example 122

{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclopropanemethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 35, using cyclopropanemethylamine. Mass spectrum (ESI): mass calculated for C23H28N2About2; 364,22; m/z found 365,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,63 (l,J=8,6, 1H), 7,40 (l,J=8,6, 1H), 7,32 (l,J=8,5, 2H), 7,30-7,25 (m, 4H), 2.63 in (t,J=7,6, 2H), 2,41 (t,J=7,2, 2H), 2,28 (l,J=6,3, 2H), 1,71 (quintet,J=7,2, 2H), 1,38 (kV,J=7,2, 2H), 0,85 (t,J=7,3, 2H), 0.88 to 0,77 (m, 2H), 0,42 (l,J=4,2, 2H), 0,05 (l,J=4,8, 2H).

Example 123

{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 38, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C23H29N3About; 363,23; m/z found 364,4[M+H] +.1H NMR (400 MHz, CDCl3): 11,44(Sirs, 1H), 7,43-7,33 (m, 2H), 7,13-7,05 (m, 6H), 3,17 (t,J=11,7, 1H), 3,10 (DD,J=7,0, 7,0, 2H), 2,99-and 2.83 (m, 4H), 2.06 to (q,J=9,8, 2H), 1,89 (l,J=12,5, 2H), 1.69 in(q,J=12,5, 1H), 1,49-1,22 (m, 7H), 1,19-of 1.05 (m, 1H).

Example 124

2-[4-(2-pyrrolidin-1-retil)phenoxy]-1H-benzoimidazol

Specified in the title compound was obtained in accordance with the procedure described in example 38, using pyrrolidine. Mass spectrum (ESI): mass calculated for C19H21N3About; 307,17; m/z found 308,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,35-7,22 (m, 2H), 7,14? 7.04 baby mortality (m, 6H), 2,79-of 2.72 (m, 2H), 2,67-to 2.57 (m, 6H), to 1.87-1.77 in (m, 4H).

Example 125

2-[4-(2-azepin-1-retil)phenoxy]-1H-benzoimidazol

Specified in the title compound was obtained in accordance with the procedure described in example 38, using azepane. Mass spectrum (ESI): mass calculated for C21H25N3About; 335,20; m/z found 336,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,38 (DD,J=3,1, 2,7, 2H), 7,11 (DD,J=3,1, 2,9, 2H), 7,10-7,00 (m, 4H), 3.25 to 3.15 in (m, 4H), 3,06 (DD,J=6,3, 5,3, 2H), 2,93 (DD,J=6,1, 4,3, 2H), 2.00 in at 1.91 (m, 4H), 1,75-to 1.67 (m, 4H).

Example 126

{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}dibutylamine

Specified in the title compound was obtained in accordance with the methodology described in PR is least 38, using dibutylamine. Mass spectrum (ESI): mass calculated for C23H31N3About; 365,5; m/z found 366,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,40-7,29 (m, 2H), 7,17-7,06 (m, 6H), 2,83-2,60 (m, 8H), 1,59 to 1.47 (m, 4H), 1,38-of 1.26 (m, 4H), of 0.93 (t,J=7,2, 6H).

Example 127

1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 38 using 4-hydroxypiperidine. Mass spectrum (ESI): mass calculated for C20H23N3About2; 337,18; m/z found 338,4 [M+H]+.1H NMR (400 MHz, CDCl3): 11,70 (Sirs, 1H), 7,50-7,44 (m, 1H), 7,33-7,27 (m, 1H), 7,24 (Sirs, 4H), 7,14-7,07 (m, 2H), 3,93 (Sirs, 1H), 3,68-to 3.58 (m, 1H), 2,97 is 2.75 (m, 4H), 2,63-2,52 (m, 2H), 2,19 (t,J=9,8, 2H), 1,94-of 1.84 (m, 2H), 1,65-and 1.54 (m, 2H).

Example 128

Methyl ester 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 38, using methyl ether piperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C22H25N3About3; 379,19; m/z found 380,4 [M+H]+.1H NMR (400 MHz, CDCl3): 11,76 (Sirs, 1H), 7,50-7,44 (m, 1H), 7.24 to 7,06 (m, 7H), 3,68 (s, 3H), 3.00 and of 2.92 (m, 2H), 2.77-to 2,70 (m, 2H), 2,53 is 2.46 (m, 2H), 2,38-of 2.28 (m, 1H), 2,10 (t, =11,1, 2H), 1,98-1,90 (m, 2H), 1,86-of 1.74 (m, 2H).

Example 129

{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 37, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C23H29N3About2; 379,23; m/z found 380,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,23 (s, 1H), 7,34-7,25 (m, 4H), 7,07 (l,J=3,5, 2H), 6,98 (l,J=9,0, 2H), 3,94 (t,J=6,4, 2H), 2,80 (t,J=6,4, 2H), 2.57 m (e,J=7,1, 2H), 2,50 (s, 2H), 1,72 (l,J=7,8, 2H), 1.55V (s, 1H), 1,20 (t,J=9,0, 4H), 0,99 (tJ=7,1, 3H).

Example 130

2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol

Specified in the title compound was obtained in accordance with the procedure described in example 35 using 4-methylpiperidine. Mass spectrum (ESI): mass calculated for C21H25N3About2; 351,19; m/z found 352,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,30 (s, 1H), 7,34-7,25 (m, 4H), was 7.08 (d,J=3,8, 2H), 6,99 (l,J=9,0, 2H), 4,08 (t,J=5,8, 2H), 2,89 (l,J=11,4, 2H), to 2.67 (t,J=5,8, 2H), 2.00 in (t,J=11,4, 2H), and 1.56 (d,J=11,5, 2H), 1,36-1,25 (m, 1H), 1,21-1,08 (m, 2H), 0.88 to (q,J=6,4, 3H).

Example 131

2-{4-[2-(4-ethylpiperazin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol

At asanee in the title compound was obtained in accordance with the methodology described in example 37 using 2-ethylpiperidine. Mass spectrum (ESI): mass calculated for C22H27N3About2; 365,21; m/z found 366,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 12.28 (s, 1H), 7,32-7,25 (m, 4H), was 7.08 (d,J=3,8, 2H), 6,99 (l,J=8,4, 2H), 4,05 (t,J=6,1, 2H), 3.00 and of 2.92 (m, 1H), 2.91 in-2,85 (m, 1H), 2,72-of 2.64 (m, 1H), 2,38-of 2.20 (m, 2H), 1,67-of 1.36 (m, 6H), 1,35-1,19 (m, 2H), 0,84 (t,J=to 7.5, 3H).

Example 132

2-[4-(2-piperidine-1-yl)ethoxy]phenoxy}-1H-benzoimidazol

Specified in the title compound was obtained in accordance with the procedure described in example 37, using piperidine. Mass spectrum (ESI): mass calculated for C20H23N3About2; 337,18; m/z found 338,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,25 (Sirs, 1H), 7,35-7,25 (m, 4H), 7,10-7,00 (m, 2H), 6,99 (l,J=9,0, 2H), 4,07 (t,J=5,9, 2H), and 2.79 (t,J=5,9, 2H), 2,43 (s, 4H), 1,55-of 1.45 (m, 4H), to 1.38 (s, 2H).

Example 133

(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol

Specified in the title compound was obtained in accordance with the procedure described in example 35, using piperidine-4-ylmethanol. Mass spectrum (ESI): mass calculated for C21H25N3About3; 367,19; m/z found 368,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,24 (s, 1H), 7,35-7,25 (m, 4H), 7,01 (s, 2H), 6,99 (l,J=7,1, 2H), and 40 (C, 1H), 4,10 (t,J=5,7, 2H), 3,25 (t,J=5,4, 2H), 2,93 (l,J=11,1, 2H), to 2.67 (t,J=5,6, 2H), 1,98(t,J=11,6, 2H), and 1.63(d,J=11,6, 2H), 1.28(in, 1H), 1,12 (l,J=9,1, 2H).

Example 134

1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 37 using 4-hydroxypiperidine. Mass spectrum (ESI): mass calculated for C20H23N3About3; 353,17; m/z found 354,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,24 (s, 1H), 7,35-7,25 (m, 4H), 7,07 (l,J=9,0, 2H), 6,99 (l,J=9,0, 2H), and 4.40 (s, 1H), 4,08 (t,J=5,8, 2H), 2,53 (s, 1H), 2,78 (l,J=11,2, 2H), 2,66 (t,J=5,8, 2H), 2,12 (t,J=10,3, 2H), 1.70 to (q,J=9,1, 2H), 1,38 (l,J=9,9, 2H).

Example 135

1-[4-(benzooxazol-2-yloxy)phenoxy]-3-pyrrolidin-1-improper-2-ol

Specified in the title compound was obtained in accordance with the procedure described in example 40, using pyrrolidine. Mass spectrum (ESI): mass calculated for C20H22N2About4; 354,16; m/z found 355,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.62 (DD,J=6,2, 2,0, 1H), 7,50 (DD,J=6,1, 2,1, 1H), 7,42 (l,J=9,1, 2H), 7,35-7,25 (m, 2H), 7,03 (l,J=9,1, 2H), 4,91 (l,J=4,5, 1H), 4,05-4,00 (m, 1H), 4,00-of 3.85 (m, 2H), 2,70 (m, 1H), 2,50-to 2.40 (m, 5H), by 1.68 (s, 4H).

Example 136

1-[2(4-benzooxazol-2-ylmethylene)ethyl]-4-phenylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 41, using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C27H28N2About3; 428,21; m/z found 429,2 [M+H]+.1H NMR (400 MHz, CD3OD): 7,62-7,58 (m, 1H), 7,54 was 7.45 (m, 3H), 7,33-7,25 (m, 6H), 7,20-to 7.15 (m, 1H), 6,91 (l,J=8,6, 2H), 4,20 (s, 2H), 4,13 (t,J=5,5, 2H), 2,87 (m, 4H), 2,66 (t,J=11,4, 2H), 2,13 (dt,J=12,8, 3,6, 2H), 1,72 (l,J=12,6, 2H).

Example 137

Amide 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]-4-phenylpiperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 41, using amide piperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C22H25N3About3; 379,19; m/z found 380,4 [M+H]+.1H NMR (400 MHz, CD3OD): to 7.64-of 7.60 (m, 1H), 7,56-7,52 (m, 1H), was 7.36-7,31 (m, 2H), 7,28 (l,J=8,7, 2H), 6,92 (l,J=8,7, 2H), 4,22 (s, 2H), 4,11 (t,J=5,6, 2H), 3,07 (l,J=12,0, 2H), and 2.79 (t,J=5,6, 2H), 2,18-of 2.15 (m, 3H), 1,80 is 1.70 (m, 4H).

Example 138

2-[4-(2-azepin-1 ylethoxy)phenoxy]-1H-benzoimidazole

Specified in the title compound was obtained in accordance with the procedure described in example 11, stage a and b in example 37, steps In and, using the hydrochloride of 1-(2-chloroethyl)azepane. the ACC-spectrum (ESI): mass, calculated for C21H25N3About2; 351,19; m/z found 352,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 12.28 (s, 1H), 7,35-7,25 (m, 4H), 7,07 (l,J=9,1, 2H), 7,00 (l,J=9,1, 2H), 4,05 (t,J=6,0, 2H), 2,86 (t,J=6,0, 2H), 2,70 (t,J=5,1, 4H), 1,65 of 1.50 (m, 8H).

Example 139

{3-[4-(1H-benzoimidazol-2-yloxy)phenoxy]propyl}dimethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 11, stage a and b in example 37, steps In and, using hydrochloride (2-chloropropyl)dimethylamine. Mass spectrum (ESI): mass calculated for C18H21N3About2; 311,16; m/z found 312,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,32-of 7.23 (m, 2H), 7,21-7,14 (m, 4H), 6.89 in-6,83 (m, 2H), 3,99-3,91 (m, 2H), of 2.51 (t,J=7,2, 2H), 2,31 (s, 6H) 2,02-of 1.95 (m, 2H).

Example 140

2-[4-(2-pyrrolidin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol

Specified in the title compound was obtained in accordance with the procedure described in example 21, stages a and b in example 35, steps In and, using pyrrolidine. Mass spectrum (ESI): mass calculated for C19H21N3About2; 323,16; m/z found 324,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,27 (Sirs, 2H), 7,15 (l,J=9,1, 4H), for 6.81 (d,J=6,8, 2H) 4,16 (t,J=5,5, 2H), 3,05 (t,J=5,5, 2H), 2,86 (Sirs, 4H), 1,92 (Sirs, 4H).

Example 141

{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}diethylamin

Specified in the title compound was obtained in accordance with the procedure described in example 21, stages a and b in example 35, steps In and, using diethylamine. Mass spectrum (ESI): mass calculated for C19H23N3About2; 326,18; m/z found 326,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,29 (Sirs, 2H), 7,18 (l,J=9,0, 2H), 7,10-7,05 (m, 2H), 6,98 (l,J=9,0, 2H), 4,03 (t,J=6,2, 2H), 2,78 (t,J=6,1, 2H), 2,55 (kV,J=7,1, 4H), and 0.98 (t,J=7,1, 6H).

Example 142

2-[4-(2-morpholine-4-yl)ethoxy]phenoxy}-1H-benzoimidazol

Specified in the title compound was obtained in accordance with the procedure described in example 21, stages a and b in example 37, steps In and, with the use of the research. Mass spectrum (ESI): mass calculated for C19H21N3About3; 339,16; m/z found 340,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,40-7,25 (m, 4H), 7,12-was 7.08 (m, 2H), 7,00 (l,J=9,0, 2H), 4,10 (t,J=5,7, 2H), to 3.58 (t,J=4,5, 4H), 2,70 (t,J=5,7, 2H), 2,52 is 2.46 (m, 4H).

Examples 143-202 and 204-229

Compounds of the present invention, the specific description which is not described in this application can be obtained in accordance with methods similar to those described in the present invention, and conducted at the discretion specialist is in this area and in accordance with the described methods. So, for example, listed in this description benzothiazoline derivatives with non 143-202 and 204-229, can be obtained in accordance with methods similar to those described for obtaining related compounds.

Example 203

[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid

Specified in the title compound was obtained in accordance with the procedures described in example 20 and example 18, using the hydrochloride of the ethyl ester sarcosine. Mass spectrum (ESI): mass calculated for C24H27N3About5S; 469,56; m/z found 470,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,02, 1H), 7,65 (l,J=8,02, 1H), 7,34-7,40 (m, 1H), 7.23 percent-7,30 (m, 3H), 6,92-6,98 (m, 2H), 4,34-of 4.44 (m, 2H), 3,92 (Sirs, 2H), 3.45 points-of 3.54 (m, 3H), 3,35 (Sirs, 1H), 3,25 (Sirs, 1H), 3,12 (s, 2H), 2,96 (s, 1H), was 2.76 (Sirs, 2H), 1,92-of 2.08 (m, 4H).

Examples 230-231 and 485

As can be seen from the context of describing the present invention, the compounds of the present invention, the specific description which is not described in this application can be obtained in accordance with methods similar to those described in the present invention and carried out at the discretion of the experts in this field and in accordance with the described methods. So, for example, listed in this description benzoimidazole derivatives in the region have the rooms 230-231 and 485, can be obtained in accordance with methods similar to those described for obtaining related compounds.

Example 250

1-[4-(benzothiazol-2-yloxy)phenyl]piperidine-4-carboxylic acid

A. Ethyl ester 1-(4-(benzyloxybenzyl)piperidine-4-carboxylic acid.

A mixture of 4-benzyloxybenzaldehyde (15.2 g, 65.3 mmol), ethyl ether isonipecotic acid (15 ml, 97 mmol) and K2CO3(13.5 g, which is 97.6 mmol) in CH3CN (300 ml) was stirred while boiling under reflux for 20 hours, the Reaction mixture was cooled to room temperature and filtered. The solvent was removed under reduced pressure and obtained a clear oil Golden brown. The oil was diluted iPrOH (100 ml) and the mixture was filtered. The solid was dried in the air and got solid white (19.7 g, yield 85%). TLC (SIO, SIS215% acetone/CH2Cl2): Rf=0,32. Mass spectrum (ESI): mass calculated for C22H27NO3; 353,2; m/z found 354,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,44 (l,J=7,1, 2H), 7,39 (t,J=7,1, 2H), 7,33 (l,J=7,2, 1H), 7,18 (l,J=8,2, 2H), 6,94 (2H,J=8,6, 2H), to 5.08 (s, 2H), 4.04 the (kV,J=7,09, 2H), 2,72 (l,J=11,5, 2H), 2,32-to 2.18 (m, 1H), 1,94 (t,J=11,6, 2H), 1,76 (l,J=10,2, 2H), 1,59 is 1.48(m, 2H), 1,17 (t,J=7,1, 3H).

C. Ethyl ester 1-(4-hydroxybenzyl)piperidine-4-carboxylic acid

Ethyl ester of 1-(4-(benzyloxybenzyl)piperidine-4-carboxylic acid (10.0 g, 28.3 mmol) was dissolved in a mixture of ethanol/ethyl acetate, 1:1, (150 ml). To the solution was added Pd on coal (10 wt.%, 503 mg) in the form of a suspension in ethanol (5.0 ml). The resulting suspension was placed in hydrogenator Parra under pressure 40 psi H2and was shaken overnight. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate was concentrated under reduced pressure to obtain a clear oil Golden brown. The oil was purified on SIO, SIS2(90 g; 50% acetone/CH2Cl2) and received solid white (2.0 g, yield 27%). TLC (SIO, SIS2, 50% acetone/CH2Cl2): Rf=0,32. Mass spectrum (ESI): mass calculated for C15H21NO3; 263,2; m/z found AZN 264.2 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 9.25 (s, 1H), 7,05 (l,J=8,4, 2H), 6,68 (l,J=8,4, 2H), 4.04 the (kV,J=7,1, 2H), 3,34 (s, 2H), 2,71 (l,J=11,5, 2H), 2,32-to 2.18 (m, 1H), 1,92 (t,J=11,6, 2H), 1,76 (l,J=10,2, 2H), 1,59 is 1.48 (m, 2H), 1,17 (t,J=7,1, 3H).

C. Ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid.

To a stirred solution of ethyl ester 1-(4-hydroxybenzyl)piperidine-4-carboxylic acid (508 mg, of 1.93 mmol) in CH3JV (15 ml) was added To a2CO3(564 mg, 4.1 mmol) and 2-chlorobenzothiazole (0,50 ml, 4.0 mmol). The suspension was heated to 80°C and was stirred overnight. actionnow the mixture was cooled to room temperature and then filtered through a layer of diatomaceous earth. The filtrate was concentrated under reduced pressure and the residue was purified on SIO, SIS2(12 g; 0-15% acetone/CH2Cl2with getting clear, colorless sticky oil (717 mg, yield 94%). TLC (SIO, SIS215% acetone/CH2Cl2): Rf=0,5. Mass spectrum (ESI): mass calculated for C22H24N2About3S; 396,2; m/z found 397,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=8,0, 1H), 7.68 per (e,J=8,0, 1H), of 7.48-7,33 (m, 5H), 7,33 (t,J=7,1, 1H), 4,06 (kV,J=7,1, 2H), 3,49 (s, 2H), was 2.76 (d,J=11,5, 2H), 2,34-2,22 (m, 1H), 2,02 (t,J=11,6, 2H), 1,80 (l,J=10,2, 2H), 1,64-and 1.54 (m, 2H), 1,18 (t,J=7,1, 3H).

D. 1-[4-(benzothiazol-2-yloxy)phenyl]piperidine-4-carboxylic acid.

To a stirred solution of ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid (663 mg, 1.7 mmol) in 25% iPrOH/H2O (20 ml) was added potassium hydroxide (206 mg, 3.1 mmol). The reaction mixture was stirred at room temperature for 20 h and the solution was treated with 1M HCl to pH 5.5. The resulting solution was extracted with 10% iPrOH/CHCl3(3×50 ml). The combined extracts were dried (MgSO4), filtered and concentrated under reduced pressure to obtain solid white (561 mg, yield 91%). Mass spectrum (ESI): mass calculated for C20H20N2About3S; 368,1; m/z found 369,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=7,6, 1H), and 69 (e, J=7,6, 1H), of 7.48-7,34 (m, 5H), 7,33 (t,J=7,1, 1H), 3,49 (s, 2H), was 2.76 (d,J=11,4, 2H), 2,22-2,11 (m, 1H), 2,02 (t,J=11,2, 2H), 1,80 (l,J=13,2, 2H), 1,62 is 1.48 (m, 2H), 1,18 (t,J=7,1, 3H).

Example 251

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-he

A. 4-(benzothiazol-2-yloxy)benzaldehyde.

To a mixture of 4-hydroxybenzaldehyde (1 g, 8.2 mmol) and 2-chlorobenzothiazole (2,03 ml, 16.4 mmol) in CH3CN (100 ml) was added Cs2CO3(5.5 g, and 17.2 mmol). The reaction mixture was stirred at 60°C for 24 h the mixture was cooled to room temperature, filtered through a layer of diatomaceous earth and concentrated under reduced pressure to obtain the crude product as an orange oil. The oil is triturated with hexane/CH2Cl2(100 ml), then a layer of solvent decantation and the mixture was concentrated under reduced pressure to obtain an orange oil, which was then purified on SIO, SIS2(120 g; 0-50% ethyl acetate/hexane)to give a solid white color (853 mg, yield 41%).1H NMR (400 MHz, CDCl3): a 10.1 (s, 1H), 7,97 for 7.78 (m, 2H), 7,78-of 7.70 (m, 2H), 7,60 is 7.50 (m, 2H), of 7.48-7,38 (m, 1H), was 7.36-7,30 (m, 1H).

Century 1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-he.

A mixture of 4-(benzothiazol-2-yloxy)benzaldehyde (500 mg, 1.9 mmol), hydrochloride of 1-piperidine-4-iparralde-2-she (440 mg, 2.2 mmol), Et3N (300 μl, 2.2 m is ol) and molecular sieves (500 mg, crushed 4Å) in Cl2CH2Cl (10 ml) was stirred at room temperature for 1 hour To the mixture was added N(SLA)3(830 mg, to 3.92 mmol). The mixture was stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(50 ml) and concentrated under reduced pressure to obtain the crude product as a yellow oil. The crude product was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2) and received a clear oil, which crystallized upon standing (287 mg, yield 36%). Mass spectrum (ESI): mass calculated for C23H25N3About2S; of 407.5; m/z found 408,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=8,0, 1H), 7,69 (l,J=8,0, 1H), 7,41-7,30 (m, 3H), 7,35-7,27 (m, 3H), 4,46-3,98 (m, 1H), 3,71 (s, 2H), 3,36 (t,J=6,9, 2H), 2,97 (l,J=11,7, 2H), 2.40 a (t,J=8,1, 2H), 2,17-of 1.97 (m, 4H), 1,81-of 1.62 (m, 4H).

Example 252

2-(2-fluoro-4-piperidine-1-ylmethylene)benzothiazole

A. (3-fluoro-4-hydroxyphenyl)piperidine-1-ylmethanone.

A solution of 3-fluoro-4-hydroxybenzoic acid (5.0 g, 32 mmol), piperidine (5 ml, 51 mmol) and EDCI (9.3 g, 49 mmol) in CH2Cl2(100 ml) was stirred at room temperature for 20 hours the Reaction mixture was added to CH2Cl2(200 ml) and washed with 1M HCl (2×100 ml). The organic layer was combined, dried (MgSO 4) and concentrated under reduced pressure to obtain a clear oil Golden brown. The oil was purified on SIO, SIS2(120 g; 0-15% acetone/CH2Cl2) and received solid white (2.4 g, yield 34%). TLC (SIO, SIS215% acetone/CH2Cl2): Rf=0,35. Mass spectrum (ESI): mass calculated for C12H14FNO2; 223,1; m/z found 224,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 10,26(s, 1H), 7,18 (l,J=11,6, 1H), 7,00 (l,J=8,3, 1H), 6,98 (t,J=8,5, 1H), 3,42 (Sirs, 4H), 1,65-of 1.45 (m, 6H).

Century 2-fluoro-4-piperidine-1-ylmethylene.

A solution of lithium aluminum hydride (1.9 g, 50 mmol) in THF (40 ml) was stirred at 5°C. To the mixture for 15 minutes was added (3-fluoro-4-hydroxyphenyl)piperidine-1-ylmethanone (2.3 g, 10.4 mmol) in THF (10 ml) and then the mixture was heated to 60°C. After 20 hours the mixture was cooled to 5°C., was added a saturated NH4Cl (200 ml) and then CH2Cl2(200 ml). The organic layer was separated, dried (MgSO4) and concentrated under reduced pressure to obtain solid white (812 mg, yield 37%). TLC (SIO, SIS2, acetone): Rf=0,22. Mass spectrum (ESI): mass calculated for C12H16FNO; 209,1; m/z found 210,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 6.58 (d,J=13,4, 1H), 6.48 in (q,J=8,2, 1H), 6,40 (t,J=9,9, 1H), 3,14 (s, 2H), 2,24 (Sirs, 4H), 1,54-of 1.30 (m, 6H).

C. 2-(2-fluoro-4-piperidine-1-ylmethylene)benzothiazole .

To a stirred solution of 2-fluoro-4-piperidine-1-ylmethylene (152 mg, 0.73 mmol) in CH3SP (10 ml) was added To a2CO3(201 mg, 1.5 mmol) and 2-chlorobenzothiazole (of 0.14 ml, 1.1 mmol). The suspension was heated to 80°C and was stirred overnight. The reaction mixture was cooled to room temperature and then filtered through diatomaceous earth. The filtrate was concentrated under reduced pressure and the residue was purified on SIO, SIS2(12 g; 0-50% acetone/CH2Cl2with getting a clear oil is Golden in color (142 mg, yield 57%). TLC (SIO, SIS2, 50% acetone/CH2Cl2): Rf=0,44. Mass spectrum (ESI): mass calculated for C19H19FN2OS; 342,1; m/z found 343,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.95 (d,J=7,9,1H), 7,69 (l,J=to 7.5, 1H), 7,56 (t,J=8,2, 1H), 7,47-to 7.32 (m, 3H), 7,44 (l,J=15,4, 1H), 3,48 (s, 2H), a 2.36 (s, 4H), 1,63 to 1.37 (m, 6H).

Example 253

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido

A. Tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid.

A mixture of (4-(benzothiazole-2-yloxy)benzaldehyde (Example 251, step A, 500 mg, 1.9 mmol), tert-butyl methyl ether piperidine-4-ylcarbamate acid (785 mg, 3.9 mmol) and molecular sieves (500 mg, crushed 4Å) in Cl2CH2Cl (10 ml) was stirred at room temperature is re within 40 minutes To the obtained reaction mixture in portions over 1.5 hours was added N(SLA)3(4×207 mg, 3.9 mmol). The reaction mixture was stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth and washed with CH2Cl2(50 ml). The filtrate was washed with saturated aqueous Panso3(1×25 ml), dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of oil is light yellow in color. The crude product was purified on SIO, SIS2(40 g; 0-5% 2M NH3in CH3HE/CH2Cl2) and received a white foam (504 mg, yield 59%). Mass spectrum (ESI): mass calculated for C24H29N3About3S; 439,6; m/z found 440,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,32-7,24 (m, 3H), of 4.44 (Sirs, 1H), 3,50 (s, 2H), 2,82 was 2.76 (m, 2H), 2,16-to 2.06 (m, 2H), 1,96-of 1.88 (m, 2H), 1,45 (s, 9H), 1,48-to 1.38 (m, 2H).

C. 1-[4-benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine.

To a solution of tert-butyl methyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid (200 mg, 0.45 mmol) in CH2Cl2(2 ml) at 0°C was added dropwise 4n HCl in dioxane (1.8 ml, 7.2 mmol). The resulting mixture was stirred at room temperature for 2 hours the Desired product was isolated by filtration and washed with Et2About (50 ml) to obtain a white powder (187 mg, yield 100%). Mass spectrum (ESI mass, calculated for C19H21N3OS; 339,5; m/z found 340,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,68-to 7.64 (m, 1H), 7,58-7,52 (m, 2H), of 7.48-7,44 (m, 1H), 7,40-7,35 (m, 2H), 7,30-7,24 (m, 1H), 7,20-7,14 (m, 1H), 4,25 (s, 2H), 3,52-of 3.46 (m, 2H), 3,36 of 3.28 (m, 1H), is 3.08-2,99 (m, 2H), 2,16-of 2.08 (m, 2H), 1,92 and 1.80 (m, 2H).

C. {1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ether acetic acid.

To a solution of dihydrochloride {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine (413 mg, 1.0 mmol) in CH2Cl2(20 ml) at room temperature was added tea (to 0.70 ml, 5.0 mmol) and then acetoxyacetyl (0.16 ml, 1.5 mmol). The resulting mixture was stirred at room temperature overnight. The reaction mixture was dissolved in CH2Cl2(100 ml), washed with saturated aqueous Panso3(1×25 ml), dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2) and received solid white (410 mg, yield 93%). Mass spectrum (ESI): mass calculated for C23H25N3About4S; 439,2; m/z found 440,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=7,8, 1H), 7,65 (l,J=8,1, 1H), 7,40-7,35 (m, 3H), 7,32-of 7.23 (m, 3H), 6,11 (l,J=8,3, 1H), 4,53, (s, 2H), 3,93-3,82 (m, 1H), 3,50 (s, 2H), 2,83 (l,J=11,9, 2H), of 2.15 (s, 3H), and 2.14 (t,J=11,9, 2H), 1.93 and (l,J =12,1, 2H), 1.56 to a 1.45 (m, 2H).

D. N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido.

To a solution of {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ester acetic acid (368 mg, 0.84 mmol) in THF (30 ml), CH3HE (10 ml) and H2O (10 ml) was added lithium hydroxide (an 80.2 mg, to 3.34 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was extracted with CH2Cl2(30 ml×3). The combined organic phases were concentrated under reduced pressure and obtained crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2), getting a solid white color (297 mg, yield 82%). Mass spectrum (ESI): mass calculated for C21H23N3About3S; 397,2; m/z found 398,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=7,8, 1H), 7,65 (l,J=8,1, 1H), 7,40-7,35 (m, 3H), 7,31-of 7.23 (m, 3H), 6,83 (l,J=8,1, 1H), 5,33 (Sirs, 1H), 3,99 (s, 2H), a 3.87 of 3.75 (m, 1H), 3,50 (s, 2H), 2,85 (l,J=11,4, 2H), and 2.14 (t,J=10,9, 2H), 1,92 (l,J=12,6, 2H), 1.56 to USD 1.43 (m, 2H).

Example 254

1-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-he

A. [4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine.

A mixture of 4-(benzothiazol-2-yloxy)benzaldehyde (5.0 g, a 19.6 mmol) and cyclopropylamine (3,35g, 58,7 mmol) in Cl2CH2Cl (80 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture in portions over 1.5 hours was added N(SLA)3(4×2.1 g, is 39.2 mmol). The resulting mixture was stirred at room temperature for 24 h, filtered through diatomaceous earth and washed with CH2Cl2(500 ml). The filtrate was washed with saturated aqueous Panso3(1×250 ml), dried (Na2SO4) and concentrated under reduced pressure to obtain the crude product as a pale yellow oil. The crude product was purified on SIO, SIS2(330 g; 0-5% CH3HE/CH2Cl2) and received solid white (3,95 g, yield 68%). Mass spectrum (ESI): mass calculated for C17H16N2OS; 296,1; m/z found 297,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,40-7,33 (m, 3H), 7,32-7,27 (m, 2H), 7,24 (t,J=8,1, 1H), 3,85 (s, 2H), 2,19-2,12 (m, 1H), 1,86 (Sirs, 1H), 0,48-0,35 (m, 4H).

C. Tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl) - carbamino acid.

To a solution of [4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine (2,96 g, 10 mmol) in CH3JV (40 ml) at room temperature was added N,N-diisopropylethylamine (3,48 ml, 20 mmol) and then tert-butyl ether (2-bromacil)carbamino acid (3,36 g, 15 mmol). The resulting mixture was heated at 60°C for but is I. The mixture was cooled and dissolved in CH2Cl2(200 ml), then washed with saturated aqueous Panso3(1×25 ml) and H2O (2×25 ml), dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of a solid of light yellow color. The crude product was purified on SIO, SIS2(120 g; 0-50% ethyl acetate/hexane) to obtain the solid white (3,44 g, yield 78%). Mass spectrum (ESI): mass calculated for C4H29N3O3S; 439,2; m/z found 440,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), 7,39-7,22 (m, 6H), 4.75 in (Sirs, 1H), 3,74 (s, 2H), 3,25 (DD,J=5,8, 6,1, 2H), 2,65 (t,J=6,3, 2H), 1,82 is 1.75 (m, 1H), USD 1.43 (s, 9H), 0,54-of 0.48 (m,' 2H), 0,43 is 0.37 (m, 2H).

C. N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine.

To a solution of tert-butyl methyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl) - carbamino acid in CH2Cl2(16 ml) at 0°C was added dropwise triperoxonane acid in dioxane (4 ml). The resulting reaction mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure to obtain the crude product as a pale yellow oil. The oil was dissolved in CH2Cl2(100 ml), washed with saturated aqueous Panso3(1×25 ml), dried (Na2SO4) and concentrated at below the nom pressure to obtain product as a clear oil. Mass spectrum (ESI): mass calculated for C19H21N3OS; 339,1; m/z found 340,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.61 (d,J=8,1, 1H), 7,37-to 7.18 (m, 6H), of 3.75 (s, 2H), was 2.76 (t,J=6,3, 2H), 2,60 (t,J=6,3, 2H), 1,98 (s, 2H), 1,79-of 1.73 (m, 1H), 0,51-of 0.45 (m, 2H), 0,42 is 0.37 (m, 2H).

D. 1-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-it.

To a solution of N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine (1.5 g, 4.4 mmol) in CH3JV (18 ml) at room temperature was added N,N-diisopropylethylamine (1,15 mg, 6,63 mmol) and then ethyl ester of 4-(R)-bromo-3-hydroxybutiric acid (1,11 g, 5.3 mmol). The resulting mixture was heated at 60°C over night. The mixture was cooled and dissolved in CH2Cl2(100 ml), then washed with saturated aqueous Panso3(1×10 ml) and H2O (2×10 ml), dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of butter, light brown. The crude product was purified HPLC with reversed phase (0-99%, 0,05% FA in H2O/CH3SP) and got a clear oil (435 mg, yield of 18.3%). Mass spectrum (ESI): mass calculated for C23H25N3O3S; 423,2; m/z found 424,3 [M+H]+.1H NMR (400 MHz, CD3OD): to 7.64 (d,J=8,1, 1H), 7,58-rate of 7.54 (m, 2H), 7,49 (l,J=8,1, 1H), 7,37-7,33 (m, 2H), 7,26 (t,J=7,6, 1H), 7,16 (t,J=7,6, 1H), 4,48 (DD,J=8,8, 12,9, 2H), 4,32 (t J=5,8, 1H), 3,84 of 3.75 (m, 1H), 3,64 of 3.56 (m, 2H), 3,38 (t,J=6,3, 2H), 3,24 (t,J=10,9, 1H), 2,73-of 2.66 (m, 1H), 2,59 (DD,J=6,3, 11,1, 1H), 2,15 (l,J=17,2, 1H), 0.79 (respectively d,J=6,6, 4H).

Example 255

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide

A. Tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid.

A mixture of 4-(benzothiazol-2-yloxy)benzaldehyde (4.4 g, and 17.2 mmol), tert-butyl ester methylpiperidin-4-ylcarbamate acid (4,06 g of 18.9 mmol) in Cl2CH2Cl (172 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture in portions over 1.5 hours was added N(SLA)3(4×1,82 g, to 34.4 mmol). The resulting mixture was stirred at room temperature for 24 h, filtered through diatomaceous earth and washed with CH2Cl2(300 ml). The filtrate was washed with saturated aqueous Panso3(1×50 ml), dried (Na2SO4) and concentrated under reduced pressure to obtain the crude product as a pale yellow oil. The crude product was purified on SIO, SIS2(330 g; 0-100% ethyl acetate/hexane) and got the foam light yellow (3.75 g, yield 48%). Mass spectrum (ESI): mass calculated for C25H31N3About3S; 453,2; m/z found 454,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,<> J=8,1, 1H), 7,41-7,35 (m, 3H), 7,33-of 7.23 (m, 3H), 4,13-of 3.94 (m, 1H), 3,53 (s, 2H), 2,93 (l,J=11,6, 2H), 2,74(with,3H), 2,08 (t,J=11,6, 2H), 1,81 was 1.69 (m, 2H), 1,65-of 1.57 (m, 2H), of 1.46 (s, 9H).

Century {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine.

To a solution of tert-butyl methyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid (3.7 g, 8.2 mmol) in CH2Cl2(41 ml) at 0°C was added dropwise 4n. HCl in dioxane (8.2 ml, with a 32.6 mmol). The resulting mixture was stirred at room temperature for 2 hours the Desired product was isolated by filtration and washed with Et2O (150 ml) to obtain a white powder (to 3.38 g, yield 97%). Mass spectrum (ESI): mass calculated for C20H23N3OS; 353,2; m/z found 354,4 [M+H]+.1H NMR (400 MHz, CDCl3): 8,92 (Sirs, 1H), 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,39-7,33 (m, 3H), 7,30-7,21 (m, 3H), 3,49 (s, 2H), 2,98-of 2.86 (m, 3H), 2.63 in (s, 3H), 2,08-to 1.98 (m, 4H), 1,84-1,71 (m, 2H).

C. N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide.

To a solution of dihydrochloride {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine (354 mg, 1.0 mmol) in CH2Cl2(20 ml) at room temperature was added tea (to 0.70 ml, 5.0 mmol) and then methanesulfonanilide (of 0.12 ml, 1.5 mmol). The resulting mixture was stirred at room temperature overnight. The mixture was dissolved in CH2Cl2(100 ml), washed with saturated aqueous Panso3 (1×25 ml), dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of a solid of light yellow color. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2with getting solid white (378 mg, yield 88%). Mass spectrum (ESI): mass calculated for C21H25N3About3S2; 431,1; m/z found 432,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,41-7,35 (m,3H), 7,33-of 7.23 (m, 3H), 3,80-3,70 (m, 1H), 3,50 (s, 2H), 2,96 (l,J=11,6, 2H), 2,82 (s, 3H), 2,80 (s, 3H), 2,08 (t,J=11,6, 2H), 1,89-to 1.77 (m, 2H), 1.70 to to 1.60 (m, 2H).

Example 256

2-{4-[4-(1H-tetrazol-5-yl)piperidine-1-ylmethyl]phenoxy}benzothiazole

A solution of 4-(benzothiazol-2-yloxy)benzaldehyde (Example 251, step A; 620 mg, 2.4 mmol), hydrochloride of 4-(1H-tetrazol-5-yl)piperidine (565 mg, 3.0 mmol) and Et3N (of 0.43 ml, 3.1 mmol) in 30% THF/CH2Cl2(35 ml) was stirred at room temperature for 30 minutes. To stir the mixture was added PA(ASO)3NR (787 mg, 3.7 mmol). After 20 hours the reaction mixture was added to 10% iPrOH/H2O (50 ml), the organic layer was separated and dried (MgSO4). The solvent was removed under reduced pressure and obtained a transparent sticky yellow oil. The resulting material was diluted with ethanol (10 ml)was heated is about 80°C and was filtered in hot condition. To the filtrate was added Et2About (10 ml) and the flask was cooled on ice. The resulting solid was filtered and received solid white (48 mg, yield 5%). Mass spectrum (ESI): mass calculated for C20H20N6OS; 392,1; m/z found 393,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.95 (d,J=7,9, 1H), of 7.70 (d,J=7,9, 1H), 7,53-to 7.35 (m, 5H), 7,33 (t,J=7,9, 1H)and 3.59 (s, 2H), 3,09-3,00 (m, 1H), 2.91 in (q,J=10,8, 2H), 2,22 (t,J=9,8, 2H), 1.85 to 1,72 (m, 2H).

Example 257

1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane

A. Tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid.

A mixture of (4-(benzothiazole-2-yloxy)benzaldehyde (2.5 g, 9.8 mmol), tert-butyl methyl ether piperazine-2-one-1-carboxylic acid (3.7 g, a 19.6 mmol) and molecular sieves (2.5 g, crushed 4Å) in Cl2CH2Cl (25 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture in portions over 1.5 hours was added N(SLA)3(4×504 mg and 19.6 mmol). The resulting mixture was stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth and washed with CH2Cl2(200 ml). The filtrate was washed with saturated aqueous Panso3(1×50 ml), dried (Na2SO4) and concentrated under reduced pressure to get neojidannogo the product in the form of a semi-solid substance is yellow. The crude product was purified on SIO, SIS2(120 g; 0-100% acetone/CH2Cl2) and received not quite white solid (1,72 g, yield 42%). Mass spectrum (ESI): mass calculated for C23H27N3About3S; 423,5; m/z found 426,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,2, 1H), to 7.67 (d,J=8,2, 1H), 7,42-7,37 (m, 3H), 7,4-7,25 (m, 3H), 3,53 (s, 2H), 3.45 points (shirt,J=4,9, 4H), 2,41 (shirt,J=4,5, 4H), of 1.46 (s, 9H).

Century 2-(4-piperazine-1-ylmethylene)benzothiazole.

To a solution of tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid (1.7 g, 4.0 mmol) in CH2Cl2(20 ml) at 0°C was added dropwise 4n. HCl in dioxane (5 ml, 20 mmol). The resulting mixture was stirred at room temperature for 2 h and then concentrated under reduced pressure to get crude product in the form of a solid white color. The crude product is triturated with Et2About (50 ml) and was isolated by filtration to obtain the desired product as white powder (1,37 g, yield 87%). Mass spectrum (ESI): mass calculated for C18H19N3OS; 325,4; m/z found 326,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,81 (l,J=8,0, 1H), to 7.77-7,72 (m, 2H), 7.62mm (l,J=8,2, 1H), EUR 7.57-7,53 (m, 2H), 7,45-7,40 (m, 1H), 7,35-7,31 (m, 1H), of 4.45 (s, 2H), 3,62 (Sirs, 8H).

C. 1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane.

To a mixture of glycolic acid (47 m is, of 0.62 mmol) and NOT (1.25 ml, of 0.62 mmol, 0.5m in DMF) in CH2Cl2(25 ml) was added 2-(4-piperazine-1-ylmethylene)benzothiazole (150 mg, 0.42 mmol) and then EDCI (150 mg, 0.79, which mmol). The resulting mixture was stirred at room temperature for 24 h, diluted with CH2Cl2(50 ml) and washed with saturated aqueous Panso3(1×20 ml). The organic layer was dried (Na2SO4) and concentrated under reduced pressure to obtain the crude product as a pale yellow oil. The crude product was purified on SIO, SIS2(40 g; 0-3% 2M NH3in CH3HE/CH2Cl2with getting a white foam (93 mg, yield 59%). Mass spectrum (ESI): mass calculated for C20H21N3About3S; 383,5; m/z found 384,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), 7.68 per (e,J=8,0, 1H), 7,45-7,25 (m, 6H), 4.16 the (l,J=4,1, 2H), 3,71-3,68 (m, 2H), 3,64-3,61 (m, 1H), 3,55 (s, 2H), 3,32-of 3.25 (m, 2H), 2,53 is 2.44 (m, 4H).

Example 258

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide

A. Tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbamino acid.

A mixture of 4-(benzothiazol-2-yloxy)benzaldehyde (1.0 g, 3.9 mmol), tert-butyl methyl ether piperidine-4-iletilerinindeki acid (1.3 g, 5.9 mmol) and molecular sieves (1.0 g, crushed 4Å) in Cl2CH2Cl (15 m is) was stirred at room temperature for 40 minutes To the obtained reaction mixture in portions over 1.5 hours was added N(SLA)3(4×412 mg, 7.8 mmol). The mixture was stirred at room temperature for 24 h, filtered through diatomaceous earth and washed with CH2Cl2(100 ml). The filtrate was washed with saturated aqueous Panso3(1×50 ml), dried (Na2SO4) and concentrated under reduced pressure to obtain the crude product as a yellow semi-solid substances. The crude product was purified on SIO, SIS2(40 g; 0-100% acetone/CH2Cl2) and received a white foam (890 mg, yield 50%). Mass spectrum (ESI): mass calculated for C25H31N3About3S; 453,6; m/z found 454,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,41 and 7.36 (m, 3H), 7,32-7,24 (m, 3H), 4,59 (Sirs, 1H), 3,50 (s, 2H), 3,06-3,00 (m, 2H), 2,94-is 2.88 (m, 2H), 1.97 of (t,J=11,4, 2H), 1,68 (l,J=11,4, 2H), of 1.44 (s, 9H), to 1.22 and 1.33(m, 2H).

Century-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine.

To a solution of tert-butyl methyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbamino acid (866 mg, 1.9 mmol) in CH2Cl2(5 ml) at 0°C was added dropwise 4n. HCl in dioxane (2.4 ml, 9.5 mmol). The resulting mixture was stirred at room temperature for 24 h and then concentrated under reduced pressure to get crude product in the form of a solid white color. Neoc is on the product triturated with Et 2About (50 ml) and was isolated by filtration to obtain the desired product as white powder (813 mg, yield 100%). Mass spectrum (ESI): mass calculated for C20H23N3OS; 353,5; m/z found 354,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,80 (l,J=8,0, 1H), 7,69 (l,J=8,6, 2H), 7,60 (l,J=8,0, 1H), 7,51 (l,J=8,6, 1H), 7,42-7,38 (m, 1H), 7,33-7,28 (m, 1H), 4,37 (s, 2H), 3,78 (shirt,J=12,7, 1H), 2H), 3,13 totaling 3.04 (m, 2H), 2,89 (l,J=6,6, 2H), 2,08-of 1.92 (m, 3H), 1,68-of 1.56 (m, 2H).

C. N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide.

To a mixture of C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine (150 mg, 0,39 mmol) in CH2Cl2(5 ml) was added Et3N (400 μl, of 2.86 mmol). The mixture was cooled to 0°C and the syringe was added CH3SO2Cl (41 μl, 0.52 mmol). The mixture was stirred at room temperature for 24 h, diluted with CH2Cl2(10 ml) and washed with saturated aqueous Panso3(1×5 ml). The organic layer was dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of a solid white color. The crude product was purified on SIO, SIS2(10 g; 0-3% 2M NH3in CH3HE/CH2Cl2with getting solid white (112 mg, yield 67%). Mass spectrum (ESI): mass calculated for C21H25N3About3S2; 431,6; m/z found 432,4 [M+H]+.1H YAM who (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,33-7,25 (m, 3H), 4,25 (shirt,J=6,6, 1H), 3,51 (s, 2H), 3.04 from (l,J=6,6, 2H), 2,96 (s, 3H), 2.91 in-2,84 (m, 2H), 1,98 (t,J=11,7, 2H), 1,74 (shirt,J=12,7, 2H), 1,60 is 1.48 (m, 2H), 1,36-1,24 (m, 2H).

Example 259

3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-he

A. cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it.

To a solution of 1-benzyl-4-piperidinol (10.3 g, 54 mmol) and ethanolamine (13.2 mg, 218 mmol) in CH3SP (20 ml) was added cyanoborohydride sodium (10.2 g, 163 mmol) and triftormetilfullerenov acid (5 ml) and the reaction mixture was stirred at 23°C for 3 days. The mixture was cooled to 0°C., was slowly added n. HCl until gas evolution stops and the resulting mixture was stirred an additional 3 hours. The mixture was filtered and the filtrate was concentrated under reduced pressure. The crude oil was again dissolved in H2O (50 ml) and the solution was podslushivaet adding 10h. Paon. The mixture was extracted with CH2Cl2(8×70 ml). United CH2Cl2the extracts were dried and concentrated under reduced pressure to get crude product (12.0 g, 95%). A solution of 2-(1-benzylpiperidine-1 ylamino)ethanol (3.6 g, of 15.3 mmol) in Cl2CH2Cl (5 ml) was treated with carbonyl diimidazol (SDI) (2.6 g, 16 mmol) and the mixture was stirred at 23°C for 30 minutes. CME is ü diluted CH 2Cl2(100 ml), washed with H2O (1×50 ml) and saturated aqueous Panso3(1×50 ml), dried and concentrated under reduced pressure to obtain 2.85 g (65%) of 3-(1-benzylpiperidine-4-yl)oxazolidin-2-it. To a solution of 3-(1-benzylpiperidine-4-yl)oxazolidin-2-she (2.3 g, 8,8 mmol) in Cl2CH2Cl (40 ml) was added α-chlorantraniliprole (1.5 g, 10.6 mmol) and the mixture was heated to 100°C for 90 minutes. The mixture was cooled to 23°C and concentrated under reduced pressure. The crude residue was dissolved in CH3HE and boiled under reflux for 1 h the Mixture was cooled to 0°C and concentrated under reduced pressure to obtain specified in the title compound (1.89 g, 99%). Mass spectrum (ESI): exact mass calculated for C8H14N2About2,m/z calculated USD 170.1; m/z found 171,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,97 (Sirs, 2H), 4,27 (DD,J=9,1, 7,8, 2H), 3,80 (TT,J=11,8, 4,2, 1H), 3,49 (DD,J=8,0, 6,6, 1H), 3,30 (shirt,J=12,7, 2H), 2,97 (dt,J=12,6, 2,3, 2H), 1,90 (DDD,J=16,6, 13,0, 4,1, 2H), 1,86 is 1.75 (m, 2H).

Century [4-(benzothiazol-2-yloxy)phenyl]methanol.

To a mixture of 4-hydroxybenzoato alcohol (12 g, 97 mmol) in CH3SP (200 ml)containing C2CO3(22 g, 159 mmol), was added 2-chlorobenzothiazole (22 g, 130 mmol) and the mixture is boiled under reflux for 72 hours the Mixture was cooled to room temperature, was filtered and to the centered under reduced pressure to obtain the crude product as a Golden oil. The crude oil was purified on SIO, SIS2(300 g; 5% acetone/CH2Cl2) to obtain a transparent and colorless oil (15 g, yield 60%). Mass spectrum (ESI): exact mass calculated for C14H11NO2S; 257,1; m/z found 258,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=7,4, 1H), 7,69 (l,J=8,0, 1H), 7,50-7,31 (m, 5H), 7,32 (t,J=to 7.5, 1H), 5,32 (t,J=5,7, 1H), 4,55 (l,J=5,7, 2H).

C. 2-(4-chloromethylene)benzothiazole.

To a mixture of [4-(benzothiazol-2-yloxy)phenyl]methanol (11 g, 43 mmol) in CH2Cl2(100 ml)containing triethylamine (9 ml, 65 mmol)at 5°C for 15 minutes was added dropwise thionyl chloride (4 ml/g, 55 mmol). The ice bath was removed, the mixture was heated to room temperature and stirred 24 hours. The mixture was once washed with saturated K2CO3(100 ml), dried (MgSO4) and concentrated under reduced pressure to obtain a black oil. The crude oil was purified on SIO, SIS2(300 g; 100% SN2Cl2) and received a clear orange oil (10 g, yield 84%). Mass spectrum (ESI): exact mass calculated for C14H10ClNOS; 275,0; m/z found 276,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.95 (d,J=7,3, 1H), of 7.70 (d,J=7,6, 1H), to 7.59 (d,J=8,6, 2H), 7,47 (l,J=8,6, 2H), 7,37 (t,J=7,4, 1H), 7,33 (t,J=to 7.5, 1H), 4,84 (s, 2H).

D. 3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-he.

To smesi-(4-chloromethylene)benzothiazole (670 mg, 2.4 mmol) in CH3JV (15 ml)containing C2CO3(544 mg, 3.9 mmol)was added cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it (355 mg, 1.7 mmol) and the mixture was heated to 60°C for 24 h the Mixture was cooled to room temperature, filtered and concentrated under reduced pressure to obtain the crude product as a Golden oil. The crude oil was purified on SIO, SIS2(12 g; acetone) and received solid white (591 mg, yield 84%). Mass spectrum (ESI): exact mass calculated for C22H23N3O3S; 409,2; m/z found 410,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,7, 1H), of 7.70 (d,J=to 7.5, 1H), of 7.48-7,37 (m, 5H), 7,33 (l,J=8,0, 1H), 4.25 in (t,J=7,7, 2H), 3,60-of 3.42 (m, 5H), 2,85 (l,J=11,5, 2H), 2,04 (t,J=11,4, 2H), 1,78 is 1.58 (m, 4H).

Example 260

4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one

A. 4-piperidine-4-Immortalis-3-one.

To a solution of 1-benzyl-4-piperidinol (10.3 g, 54 mmol) and ethanolamine (13.2 mg, 218 mmol) in CH3SP (20 ml) was added cyanoborohydride sodium (10.2 g, 163 mmol) and triftormetilfullerenov acid (5 ml) and the reaction mixture was stirred at 23°C for 3 days. The mixture was cooled to 0°C., was slowly added n. HCl until gas evolution stops and the resulting mixture was stirred an additional 3 hours. The mixture was filtered and Phi is Trat concentrated under reduced pressure. The crude oil was again dissolved in H2O (50 ml) and the solution was podslushivaet adding 10h. Paon. The mixture was extracted with CH2Cl2(8×70 ml). United CH2Cl2the extracts were dried and concentrated under reduced pressure to obtain 12.0 g (yield 95%) of the crude product. Solution (0°C) 2-(1-benzylpiperidine-4-ylamino)ethanol (2,13 g, 9.1 mmol) in ethanol (11 ml) and H2O (5 ml) were simultaneously treated with chloracetamide (1.8 ml, 22.7 mmol) and 35% aqueous NaOH solution and the mixture was stirred at a temperature below 20°C for 3 hours. The reaction mixture was diluted with H2O (20 ml) and was extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with saturated salt solution, dried and concentrated to obtain to 1.83 g (yield 66%) of 4-(1-benzylpiperidine-4-yl)morpholine-3-one. To a solution of 4-(1-benzylpiperidine-4-yl)morpholine-3-one (1.1 g, 3.9 mmol) in Cl2CH2Cl (20 ml) was added α-chlorantraniliprole (660 mg, 4.6 mmol) and the reaction mixture was heated to 100°C for 16 hours the Mixture was cooled to 23°C and concentrated under reduced pressure. The crude substance was purified on SIO, SIS2(12 g, 0-10% 2M ammonia in CH3HE/CH2Cl2) to obtain 282 mg (yield 53%) of 4-piperidine-4-Immortalis-3-one. Mass spectrum (ESI): exact mass calculated for C8H14N2About2,m/z, 184,1; m/z found 185,4 [M+H]+ .1H NMR (400 MHz, CDCl3): and 3.72 (s, 2H), 2,94 (t,J=6,6, 2H), by 2.55 (t,J=3.6V, 2H), 2,46 (TT,J=10,3, 3,7, 1H), 1,92 (DD,J=12,3, 2,3, 2H), 1,82 is 1.70 (m, 2H), 1.70 to to 1.60 (m, 1H), 1,40-1,02 (m, 4H).

Century 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one.

Specified in the title compound was obtained as described in example 259, step D. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S1; 423,16; m/z found 424,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,6, 1H), of 7.70 (DD,J=7,9, 0,7, 1H), 7,45-7,40 (m, 2H), was 7.36-7,28 (m, 4H), 4,57 (TT,J=12,1, 4,2, 1H), 4,22 (s, 2H), 3,90 (t,J=4,9, 2H), of 3.56 (s, 2H), 3,34 (t,J=5,1, 2H), 3,01 (shirt,J=11,6, 2H), 2,18 (DDD,J=11,7, 11,7, 2,2, 2H), 1,79 (dddd,J=12,1, 12,1, 12,0, 3,8, 2H), 1,72-of 1.65 (m, 2H).

Example 261

(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he

A. the Acetate salt of (R)-4-hydroxy-1-piperidine-4-iparralde-2-it.

A solution of 4-amino-1-benzylpiperidine (1.0 g, 5.2 mmol) and N,N-diisopropylethylamine (2,3 mg of 13.1 mmol) in CH3SP (12 ml) was treated with (R)-4-bromo-3-hydroxybutyrate (1.4 g, 6.8 mmol) and the mixture was heated at 65°C for 48 hours the Mixture was cooled, diluted with ethyl acetate (70 ml) and washed with H2O (20 ml). The organic layer was dried, concentrated under reduced pressure and then the crude residue was purified on SIO, SIS2(12 g, 0-5% 2M ammonia in SN 3HE/CH2Cl2). The product was dissolved in ethanol (20 ml) and was heated up to 80°C for 48 hours the Mixture was concentrated under reduced pressure and the crude residue was purified on SIO, SIS2(12 g, 0-5% 2M ammonia in CH3HE/CH2Cl2with getting 346 mg (yield 25%) 1-(1-benzylpiperidine-4-yl)-4-hydroxypyrrolidine-2-it. A solution of 1-(1-benzylpiperidine-4-yl)-4-hydroxypyrrolidine-2-it (346 mg, 1.3 mmol) in ethanol (7 ml) was treated with Pd(OH)2(60 mg), the mixture was loaded into a Parr apparatus under hydrogen pressure of 50 psi and was stirred for 5 days. The mixture was filtered through diatomaceous earth and concentrated to obtain 280 mg (yield 92%) indicated in the title compound, which was used in the subsequent reactions without purification. Mass spectrum (ESI): exact mass calculated for C9H16N2About2,184,1; m/z found 185,2 [M+H]+.

C. (R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he.

Specified in the title compound was obtained as described in example 24, using the acetate salt of (R)-4-hydroxy-1-piperidine-4-iparralde-2-it. Mass spectrum (ESI): exact mass calculated for C24H27N3O4S1: 453,2; m/z found 454,5 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,69 (DD,J=8,0, 0,7, 1H), 7,42 (dt,J=8,5, 1,3, 1H), 7,34-7,27 (m, 5H), 7,02-6,97 (m, 2H), 4,58-a 4.53 (m, 1H), 4,8-Android 4.04 (m, 3H), 3,62 (DD,J=10,7, 5,6, 1H), 3,34 (DD,J=10,7, 2,2, 1H), 3,15-is 3.08 (m, 1H), 2,87 (t,J=5,7, 2H), 2,75 (DD,J=17,2, 6,6, 1H), 2,44 (DD,J=17,2, 2,6, 1H), 2,34-of 2.24 (m, 2H), 1,90 by 1.68 (m, 3H).

Example 262

2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole

A. [4-(benzothiazol-2-yloxy)phenyl]acetaldehyde.

A solution of methyl ester (4-hydroxyphenyl)acetic acid (11.2 g, 62 mmol) and 2-chlorobenzothiazole (9.5 g, 56 mmol) in CH3SP worked fine powder Cs2CO3(27 g, 84 mmol) and the resulting mixture was stirred at 40°C for 17 h at 60°C for 2 h, the Reaction mixture was filtered through diatomaceous earth and the filtrate was concentrated under reduced pressure. The crude solid was purified by dissolving in ethyl acetate (350 ml) and washing with 10% Paon (3×30 ml), 0.5m citric acid (1×30 ml), saturated aqueous Panso3(1×30 ml) and saturated salt solution (1×30 ml), then dried over Na2SO4, filtered and concentrated under reduced pressure to obtain 16 g (yield 95%) of methyl ester [4-(benzothiazol-2-yloxy)phenyl]acetic acid in a solid white color. A solution of methyl ester [4-(benzothiazol-2-yloxy)phenyl]acetic acid (5.4 g, 18 mmol) in 80 ml of toluene at -90°C was treated dropwise 1.0m solution of hydride diisobutylaluminum in hexane (27 ml, 27 mmol). Rea is operating, the mixture was slowly heated within 30 minutes to -68°C and then the reaction was suppressed by the addition of methanol (2.0 ml). The reaction mixture was heated to -20°C, diluted with diethyl ether (100 ml) and 2.0m HCl (60 ml) and then intensively stirred for 30 minutes. The organic layer was separated, washed with saturated aqueous Panso3, dried over Na2SO4, filtered and concentrated to obtain specified in the connection header (4,84 g, yield 99%).

Century 2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}-phenoxy)benzothiazole.

A solution of [4-(benzothiazol-2-yloxy)phenyl]-acetaldehyde (628 mg, 2.3 mmol) and 4-(1H-tetrazol-5-yl)piperidine (443 mg, 2.34 mmol) in CH2Cl2(10 ml)containing triethylamine (360 μl, 2.6 mmol)was treated with triacetoxyborohydride sodium (599 mg, 2.7 mmol) and the mixture was stirred at room temperature for 24 h the Mixture was washed with saturated aqueous Panso3(15 ml), dried (MgSO4) and concentrated under reduced pressure to obtain solid white. The solid is washed with diethyl ether and air-dried to obtain the product in a solid white color (214 mg, yield 23%). Mass spectrum (ESI): mass calculated for C21H22N6OS; 406,2; m/z found 407,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.93 (d,J=7,9, 1H), 7,69 (l,J=7,7, 1H), of 7.48-7,30 (m, 6H), 3,10 (l,J=11,6, 2H), is 3.08-of 2.97 (m, 1H), 2,87 (t,J=6,7, 2H), 2,72 (t,J=8,6, 2H), 2,34 (t,J=11,0, 2H), 2,01 (l,J=11,2, 2H), 1,79 (kV,J=9,9, 2H).

<> Example 263

(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol

Specified in the title compound was obtained in accordance with the procedure described in example 24, using piperidine-2-ylmethanol. Mass spectrum (ESI): mass calculated for C21H24N2About3S; 384,2; m/z found 385,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to $ 7.91 (d,J=7,9, 1H), 7.68 per (e,J=8,0, 1H), 7,42 (t,J=7,3, 1H), 7,37 (l,J=9,0, 2H), 7,31 (t,J=8,1, 1H), 7,05 (l,J=9,1, 2H), 4,43 (t,J=5,3, 1H), 4,08 (t,J=6,2, 2H), 3,60-3,51 (m, 1H), 3,48-3,39 (m, 1H), 3,17-to 3.09 (m, 1H), 2,94-2,84 (m, 1H), 2,80-2,70 (m, 1H), 2,33 (t,J=10,4, 2H), 1,62 (l,J=9,3, 2H), 1,58 to 1.47 (m, 1H), 1,47-of 1.35 (m, 1H), 1,35-1,20 (m, 2H).

Example 264

Ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 24, using ethyl ether (1H-tetrazol-5-yl)acetic acid. Mass spectrum (ESI): mass calculated for C20H19N5About4S; 425,1; m/z found 426,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to $ 7.91 (d,J=8,0, 1H), to 7.67 (d,J=7,6, 1H), 7,46 and 7.36 (m, 3H), 7,32 (t,J=8,4, 1H), 7,03 (l,J=9,1, 2H), 4,88 (t,J=5,0, 2H), 4,43 (t,J=5,0, 2H), 4,35 (s, 2H), 4,14 (kV,J=7,1, 2H), 1,20 (t,J=7,1, 3H).

Example 265

(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol

Specified in the title compound was obtained in accordance with the procedure described in example 24, using piperidine-3-ylmethanol. Mass spectrum (ESI): exact mass calculated for C21H24N2About3S1; 384,2; m/z found 385,1 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=8,1, 1H), 7.68 per (e,J=7,9, 1H), 7,42 (dt,J=8,4, 1,2, 1H), 7,34-7,26 (m, 3H), 7,02-6,97 (m, 2H), 4,15 (t,J=5,9, 2H), 3,68 (DD,J=10,6, 5,2, 1H), of 3.56 (DD,J=10,4, 6,3, 1H), 3.00 and (l,J=5,3, 1H), 2,84 (t,J=5,9, 2H), 2,83-and 2.79 (m, 1H), 2,75-2,60 (m, 1H), 2,30 (t,J=9,5, 1H), 2,16 (t,J=9,5, 1H), 1,92-of 1.78 (m,2H), 1.77 in by 1.68 (m, 1H), 1,68 is 1.60 (m, 1H), 1,24-1,12 (m, 1H).

Example 266

Hydrochloride of 2-{4-[2-(5-piperidine-4-intersol-2-yl)ethoxy]phenoxy}benzothiazole

A. Tert-butyl ester 4-(2-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2H-tetrazol-5-yl)piperidine-1-carboxylic acid.

To a stirred solution of 2-[4-(2-bromoethoxy)phenoxy]benzothiazole (Example 9; 500 mg, 1.4 mmol) and tert-butyl ester 4-(2H-tetrazol-5-yl)piperidine-4-carboxylic acid (404 mg, 1.6 mmol) in CH3SP (10 ml) was added Cs2CO3(543 mg, 1.7 mmol). The mixture was heated at 60°C for 20 h and then filtered. The filtrate was concentrated under reduced pressure to obtain a clear oil, Golden color, which was purified on SIO, SIS (40 g; 0-15% acetone/CH2Cl2), getting a solid white color (483 mg, yield 65%). TLC (SIO, SIS215% acetone/CH2Cl2): Rf=0,84. Mass spectrum (ESI): mass calculated for C26H30N6About4S; 522,2; m/z found 523,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.90 (d,J=7,7, 1H), to 7.67 (d,J=7,9, 1H), 7,42 (t,J=7,1, 1H), was 7.36 (d,J=6,8, 2H), 7,31 (t,J=8,1, 1H), 7,01 (l,J=6,9, 2H), of 5.05 (t,J=4,7, 2H), 4,57 (t,J=4,8, 2H), 3,92 (l,J=12,4, 2H), 3,20-of 3.12 (m, 1H), 2,96 (Sirs, 2H), 1,97 (DD,J=13,3, 3, 2H), 1,65-of 1.52 (m, 2H), 1,40 (s, 9H).

Century Hydrochloride, 2-{4-[2-(5-piperidine-4-intersol-2-yl)ethoxy]phenoxy}benzothiazole.

To a stirred solution of tert-butyl ester 4-(2-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2H-tetrazol-5-yl)piperidine-1-carboxylic acid (440 mg, 0.84 mmol) in 88% formic acid (7.5 ml) was added concentrated HCl (75 μl, 0,009 mmol). The mixture was stirred at room temperature for 20 h and then concentrated under reduced pressure to obtain colorless transparent oil. The oil was dried under high vacuum for 2 h and received solid white (337 mg, yield 99%). Mass spectrum (ESI): mass calculated for C21H22N6O2S; 422,2; m/z found 423,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=7,9, 1H), to 7.67 (d,J=8,0, 1H), 7,42 (t,J=7,8, 1H), 7,39 (l,J=9,4, 2H), 7,32 (t,J=7,4, 1H), 5,08 (is, J=4,7, 2H), 4,58 (t,J=4,8, 2H), 3,40-up 3.22 (m, 4H), 3,03 (kV,J=15,1, 2H), 2,16 (l,J=14,1, 2H), 1,92 (kV,J=14,3, 2H).

Example 267

7-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]-4-Spiro[3-phtalic]piperidine

Specified in the title compound was obtained in accordance with the procedure described in example 24 using 4-Spiro[3-phtalic]piperidine. Mass spectrum (ESI): mass calculated for C27H24N2About4S; 472,2; m/z found 473,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=7,9, 1H), 7,83 (l,J=7,7, 1H), 7,82 to 7.75 (m, 2H), of 7.70 (d,J=10,2, 1H), to 7.61 (t,J=11,6, 1H), of 7.48-7,38 (m, 3H), 7,32 (t,J=8,2, 1H), 7,10 (l,J=9,1, 2H), 4,19 (t,J=5,7, 2H), 3,05 (l,J=13,0, 2H), 2,86 (t,J=5,6, 2H), 2,50 is 2.44 (m, 2H), 2,28 (t,J=13,5, 2H), 1,65 (l,J=12,5, 2H).

Example 268

Ethyl ester of 1-{3-[4-(benzothiazol-2-yloxy)phenyl]propyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 35, using ethyl ether piperidine-4-carboxylic acid for stage and 2-chlorobenzothiazole for stage C. Mass spectrum (ESI): mass calculated for C24H28N2About3S; 424,2; m/z found 425,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=7,9, 1H), 7.68 per (e,J=8,0, 1H), 7,43 (t,J=8,1, 1H), 7,38-7,28 (m, 5H), 4,05 (kV,J=7,1, 2H), 2,78 (l,J=11,, 2H), 2.63 in (t,J=to 7.5, 2H), 2,25 (t,J=7,0, 3H), 1.93 and (t,J=13,2, 2H), 1,84 by 1.68 (m, 4H), and 1.54 (kV,J=14,9, 2H), 1,18 (t,J=7,1, 3H).

Example 269

Hydrochloride of 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine

A. Tert-butyl ether [2-(4-hydroxyphenyl)ethyl]carbamino acid.

To perelyaeva solution of di-tert-butyldiethanolamine (34,2 g, 157 mmol) in THF (200 ml) was added tyramine (21,3 g, 155 mmol) in THF (100 ml) for 1 h and the Mixture was stirred for 2.5 h and then concentrated under reduced pressure to obtain a clear oil, Golden color, which was purified on SIO, SIS2(300 g; 0-25% acetone/CH2Cl2). The desired fractions were combined and concentrated under reduced pressure to obtain product as a clear oil pink (37 g, yield 100%). TLC (SIO, SIS2with 5% acetone/CH2Cl2): Rf=0,31. Mass spectrum (ESI): mass calculated for C13H19NO3; 237,1; m/z found of 260.2 [M+PA]+.1H NMR (400 MHz, DMSO-d6): 9,16 (s, 1H), of 6.96 (d,J=8,4, 2H), PC 6.82 (s, 1H), 6,66 (l,J=8,4, 2H), 3,05 (kV,J=8,3, 2H), 2,56 (t,J=8,1, 2H), of 1.37 (s, 9H).

C. Tert-butyl ether {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}carbamino acid.

Specified in the title compound was obtained in the form of solids, white (9 g, yield 56%) in accordance with the procedure described in example 30, step B, the BL is using tert-butyl ester [2-(4-hydroxyphenyl)ethyl]carbamino acid. TLC (SIO, SIS2CH2Cl2): Rf=0,19. Mass spectrum (ESI): mass calculated for C20H22N2About3S; 370,1; m/z found 371,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=7,9, 1H), 7.68 per (e,J=8,0, 1H), of 7.48-7,30 (m, 6H), 7,34 (t,J=7,8, 1H), 3,09 (l,J=7,1, 2H), 2,75 (t,J=7,4, 2H), to 1.38 (s, 9H).

C. the Hydrochloride of 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine.

Specified in the title compound was obtained in a solid white color (6.4 g, yield 100%) in accordance with the procedure described in example 266, step C. Mass spectrum (ESI): mass calculated for C15H14N2OS; 270,1; m/z found 271,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,05 (Sirs, 2H), 7,94 (l,J=7,8, 1H), 7.68 per (e,J=7,8, 1H), 7,53-7,39 (m, 5H), 7,34 (t,J=7,9, 1H), 3,09 (t,J=6,9, 2H), 2.95 and (t,J=8,6, 2H).

Example 270

2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethoxy]phenoxy)benzothiazole

A. Methyl ester [4-(benzothiazol-2-yloxy)phenoxy]acetic acid.

To a stirred mixture of sodium hydride (7.5 g, 187,5 mmol) in DMSO (100 ml) for 30 minutes was added hydroquinone (10.0 g, 91,2 mmol). Then the mixture was heated up to 80°C for 2 hours and cooled to room temperature. To stir the mixture for 30 minutes was added 2-chlorobenzothiazole (11.3 ml of 91.3 mmol) and the mixture was stirred at room temperature in them is giving 24 hours To the mixture was added methyl-2-bromoacetate (86 ml, the 90.8 mmol) for 30 minutes and the mixture was stirred for 24 hours To the mixture was added H2O (1 l) and the product was extracted with Et2About (2×500 ml), dried (MgSO4) and concentrated under reduced pressure to obtain a beige solid. The solid was stirred in CH2Cl2(200 ml) and filtered to obtain the product in a solid white color (24.2 g, yield 84%). Mass spectrum (ESI): mass calculated for C16H13N2O4S; 315,1; m/z found 316,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 7.92 (d,J=8,0, 1H), 7,66 (l,J=8,1, 1H), 7,47-7,40 (m, 3H), 7,32 (t,J=to 7.5, 1H), 7,07 (l,J=8,6, 2H), to 4.87 (s, 2H), of 3.73 (s, 3H).

Century [4-(benzothiazol-2-yloxy)phenoxy]acetaldehyde.

To a stirred solution of methyl ester [4-(benzothiazol-2-yloxy)phenoxy]acetic acid (1.0 g, 3,17 mmol) in THF (15 ml) at -78°C was added DIBAL-H (5 ml, 5 mmol), maintaining the temperature below -75°C. the Mixture was stirred at -72°C for 4 h, the reaction was suppressed by the addition of H2O (10 ml), then the mixture was extracted with CH2Cl2(2×10 ml), dried (MgSO4) and concentrated under reduced pressure, obtaining a clear oil is Golden in color (708 mg, yield 78%). Mass spectrum (ESI): mass calculated for C15H11NO3S; 285,1; m/z found 286,3 [M+H]+.

C. 2-(4-{2-[4-(1H-tetrazol-5-yl)PIP is ridin-1-yl]ethoxy]-phenoxy)benzothiazole .

Specified in the title compound was obtained in accordance with the procedure described in example 262, step b using 4-(1H-tetrazol-5-yl)piperidine. Mass spectrum (ESI): mass calculated for C21H22N6About2S; 422,2; m/z found 422,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.93 (d,J=7,8, 1H), 7.68 per (e,J=7,9, 1H), 7,49-7,40 (m, 3H), 7,33 (t,J=7,3, 1H), 7,14 (l,J=9,0, 2H), 4,43 (t,J=4,3, 2H), 3,62-of 3.43 (m, 4H), 3.25 to 3,10 (m, 3H), 2,25 (l,J=12,0, 2H), 2,18-2,02 (m, 2H).

Example 271

2-(4-piperidine-1-ylmethylene)benzooxazol

A. 4-piperidine-1-ylmethylene.

A mixture of 4-hydroxybenzaldehyde (10 g, 82 mmol), piperidine (16 ml, 164 mmol) and molecular sieves (10 g, milled, 4E) Cl2CH2Cl (150 ml) was stirred at room temperature for 40 minutes To the mixture in portions over 1.5 hours was added N(SLA)3(7×5 g, 164 mmol). The reaction mixture was stirred at room temperature for 24 h the mixture was diluted with CH2Cl2(300 ml), filtered through kieselguhr and again washed CH2Cl2(100 ml). The filtrate was washed with saturated aqueous Panso3(3×150 ml), was extracted with a mixture of 25% isopropanol/CHCl3, then was dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of a semi-solid which CSOs substances orange. The crude product was purified on SIO, SIS2(120 g; 0-100% acetone/CH2Cl2) and received solid yellow (is 3.08 g, yield 48%). Mass spectrum (ESI): mass calculated for C12H17NO; 191,1; m/z found 192,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,18 (l,J=8,4, 2H), 6.75 in (q,J=8,4, 2H), 3,83 (s, 2H), 2,81 (Sirs, 4H), 1.77 in (quintet,J=5,7, 4H), and 1.54 (Sirs, 2H).

Century 2-(4-piperidine-1-ylmethylene)benzooxazol.

Specified in the title compound was obtained in accordance with the procedure described in example 13, step B, using 4-piperidine-1-ylmethylene. Mass spectrum (ESI): mass calculated for C19H20N2About2S; 308,2; m/z found 309,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.64 (d,J=3.1 Hz, 1H), 7,52 (d,J=a 8.9 Hz, 1H), and 7.3 (kV,J=8,3 Hz, 4H), 7,34-7,26 (m, 2H), 3.45 points (s, 2H), 2,33 (Sirs, 4H), 1,57 of 1.46 (m, 4H), 1,44-of 1.32 (m, 2H).

Example 272

[4-(benzothiazol-2-yloxy)benzyl}cyclohexylethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using cyclohexylethylamine. Mass spectrum (ESI): mass calculated for C22H26N2OS; 366,2; m/z found 367,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.93 (d,J=8,5, 1H), of 7.70 (d,J=8,0, 1H), 7,45 (t,J=8,5, 3H), 7,37 (l,J=8,6, 2H), 7,33 (t,J=8,3, 1H), 3,63 (s, 2H), 2,58-to 2.41 (m, 3H), 1,7 (t, J=11,9, 4H), 1,58 (l,J=12,1, 1H), 1.32 to a 1.01 (m, 5H), of 0.95 (t,J=7,1, 3H).

Example 273

[4-(benzothiazol-2-yloxy)benzyl]cyclopropanemethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using (2-cyclopropylethyl)ethylamine. Mass spectrum (ESI): mass calculated for C21H24N2OS; 352,2; m/z found 353,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,0, 1H), of 7.70 (d,J=8,1, 1H), 7,45 (t,J=8,5, 3H), 7,39 (l,J=8,6, 2H), 7,33 (t,J=8,0, 1H), 3,66 (s, 2H), 2,53 is 2.44 (m, 3H), 2,32 (l,J=6,5, 2H), 1,54-of 1.42 (m, 2H), 1.32 to a 1.01 (m, 5H), of 0.85 (d,J=7,3, 4H), 0,45 (l,J=9,7, 2H), 0,06 (t,J=6,2, 2H).

Example 274

Amide 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using amide piperidine-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C20H21N3About2S; 367,1; m/z found 368,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,4, 1H), of 7.70 (d,J=7,9, 1H), of 7.48-7,38 (m, 5H), 7,33 (l,J=7,1, 1H), 7,22 (s, 1H), 6.73 x (s, 1H), 3,49 (s, 2H), 2,83 (l,J=11,4, 2H), 2,14-2,02 (m, 1H), 2.00 in of 1.93 (m, 2H), 1,73-of 1.62 (m, 2H), 1,58 (t,J=15,4, 2H).

Example 275

1'-[4-(is isothiazol-2-yloxy)benzyl]-[1,4']bipyridinyl-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using [1,4']bipyridinyl-2-it. Mass spectrum (ESI): mass calculated for C24H27N3About2S; UAH 421,2; m/z found 422,5 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,8, 1H), of 7.70 (d,J=8,6, 1H), of 7.48-7,38 (m, 5H), 7,33 (l,J=9,0, 1H), 4,37-of 4.25 (m, 1H), 3,52 (s, 2H), and 3.16 (t,J=5,2, 2H), 2,89 (l,J=11,2, 2H), 2,22 (t,J=6,6, 2H), 2,03 (t,J=11,1, 2H), 1,78 is 1.58 (m, 6H), 1,45 (l,J=10,8, 2H).

Example 276

{4-[4-(benzothiazol-2-yloxy)benzyl}piperazine-1-yl}pyridine-3-ylmethanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using piperazine-1-espiridion-3-ylmethanone. Mass spectrum (ESI): mass calculated for C24H22N4About2S; 430,2; m/z found 431,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,65 (l,J=4,8, 1H), 8,61 (l,J=1,9, 1H), 7,94 (l,J=7,9, 1H), to 7.84 (d,J=7,8, 1H), 7,69 (l,J=,8,0, 1H), 7,60-7,40 (m, 6H), 7,33 (l,J=8,3, 1H), 3,64 (Sirs, 2H), to 3.58 (s, 2H), 3,37 (Sirs, 2H), 2,41 (Sirs, 4H).

Example 277

Tert-butyl ether ({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 25, stage D, using tert-butyl ether piperidine-4-iletilerinindeki acid. Mass spectrum (ESI): mass calculated for C25H32N3About3S; 453,2; m/z found 454,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,3, 1H), of 7.70 (d,J=7,9, 1H), of 7.48-7,37 (m, 5H), 7,33 (l,J=8,2, 1H), 6,85 (t,J=5,9, 1H), 3,48 (s, 2H), 2,86 was 2.76 (m, 4H), 1,90(t,J=11,1, 2H), and 1.56 (d,J=11,8, 2H), 1,37 (s, 10H), 1,11 (t,J=9,9, 2H).

Example 278

Methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbamino acid

Specified in the title compound was obtained in accordance with the method described in example 258, step C, using methylcarbamate. Mass spectrum (ESI): mass calculated for C22H25N3About3S; 411,2; m/z found 412,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,9, 1H), of 7.70 (d,J=8,0, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (l,J=8,0, 1H), 7,17 (t,J=5,6, 1H), 3,51 (s, 3H), of 3.48 (s, 2H), 2,87 (t,J=6,2, 2H), 2,80 (l,J=11,1, 2H), 1,90 (t,J=10,5, 2H), 1,60 (t,J=12,8, 2H), 1,38 (Sirs, 1H), 1,20 was 1.06 (m, 2H).

Example 279

Tert-butyl ether N-{C-[[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl]methylaminomethyl}carbamino acid

To a stirred solution of C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine (Example 258, step In, 657 mg, 1.5 m is ol) in CH 2Cl2(15 ml)containing triethylamine (1 ml, 7.2 mmol), was added tert-butyl ether N-(sulphonylchloride)carbamino acid (440 mg, 2.1 mmol). The mixture was stirred for 48 hours, was dissolved in CH2Cl2(50 ml), then washed with H2O (75 ml), dried (MgSO4) and concentrated under reduced pressure to obtain a transparent, colorless oil. The oil was purified on SIO, SIS2(12 g; 0-50% acetone/CH2Cl2) and the desired fractions were combined and concentrated under reduced pressure to obtain solid white (112 mg, yield 14%). TLC (SIO, SIS2, 50% acetone/CH2Cl2): Rf=0,40. Mass spectrum (ESI): mass calculated for C25H32N4O5S2; 532,2; m/z found 533,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): a 10.74 (Sirs, 1H), of 7.90 (d,J=7,9, 1H), 7,66 (l,J=8,0, 1H), 7,54 (Sirs, 1H), 7,44-7,34 (m, 5H), 7,30 (m,J=8,3, 1H), 3,48 (s, 2H), 2,84-2,70 (m, 4H), 1,90 (t,J=10,4, 2H), 1,64 (l,J=11,4, 2H), 1,38(s, 10H), 1,16-1,02 (m, 2H).

Example 280

The hydrochloride of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}sulphonamide

Specified in the title compound was obtained from the compound of example 279 in accordance with the procedure described in example 266, step C. Mass spectrum (ESI): mass calculated for C20H24N4About3S2; 432,1; m/z found 433,4 [M+H]+ .1H NMR (400 MHz, DMSO-d6): 10,08 (Sirs, 1H), 7,80 (l,J=8,2, 1H), 7,76-to 7.68 (m, 3H), 7,58 (l,J=8,6, 2H), 7,45 (t,J=8,4, 2H), was 7.36 (t,J=8,8, 2H), 6,70-6,50 (Sirs, 2H), 4,33 (l,J=5,4, 2H), 3.00 and-2,86 (Sirs, 1H), 2,77 (t,J=6,2, 2H), 1.91 a (l,J=13,4, 2H), 1,71 (Sirs, 1H), 1,50-of 1.36 (m, 2H), 1,34-of 1.26 (m, 1H).

Example 281

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}ndimethylacetamide

Specified in the title compound was obtained in accordance with the method described in example 258, step C, using acetylchloride. Mass spectrum (ESI): mass calculated for C22H25N3About2S; 395,2; m/z found 396,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,8, 1H), 7,83 (t,J=5,5, 1H), of 7.70 (d,J=8,0, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (l,J=8,2, 1H), 3,48 (s, 2H), 2,93 (t,J=6,2, 2H), 2,81 (l,J=11,4, 2H), 1.91 a (t,J=11,3, 2H), 1,80 (s, 3H), 1.61 of (l,J=11,0, 2H), 1,38 (Sirs, 1H), 1,20 was 1.06 (m, 2H).

Example 282

{1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-yl}acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using ethyl ether piperidine-4-luxusni acid in example 250, step D. Mass spectrum (ESI): mass calculated for C21H22N2About3S; 382,1; m/z found 383,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 10,1 (Shi is .c, 1H), 7,97 (l,J=7,9, 1H), of 7.70 (d,J=7,6, 3H), 7,58 (Sirs, 2H), 7,45 (t,J=7,2, 1H), was 7.36 (t,J=7,3, 1H), or 4.31 (Sirs, 1H), 2,98 (Sirs, 3H), 2,20 (l,J=5,6, 3H), 1,87 (Sirs, 4H)and 1.51 (Sirs, 2H).

Example 283

({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbarnoyl)methyl ester acetic acid

Specified in the title compound was obtained in accordance with the method described in example 258, step D, using [(piperidine-4-ylmethyl)carbarnoyl]methyl ester of acetic acid and in accordance with the procedure described in example 253, step D. Mass spectrum (ESI): mass calculated for C24H27N3About4S; 453,2; m/z found 454,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,01 (t,J=5,8, 1H), 7,94 (l,J=to 7.5, 1H), of 7.70 (d,J=8,0, 1H), 7,80 was 7.36 (m, 5H), 7,33 (t,J=7,2, 1H), 4,43 (s, 2H), 3,48 (s, 2H), 2,98 (t,J=6,3, 2H), 2,81 (l,J=11,4, 2H), 2,08 (s, 3H), 1.91 a (t,J=11,2, 2H), 1,60 (l,J=11,2, 2H), 1,42 (Sirs, 1H), 1,20-1,08 (m, 2H).

Example 284

Tert-butyl ether [2-({1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-ylmethyl}carbarnoyl)cyclobutyl]carbamino acid

Specified in the title compound was obtained from the compound of example 258, step In, in accordance with the procedure described in example 257, step C, using 2-tert-butoxycarbonylmethylene acid. Mass spectrum (ESI): m the SSA, calculated for C30H38N4About4S; 550,3; m/z found 551,5 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,9, 1H), of 7.70 (d,J=8,0, 1H), 7,47-7,35 (m, 7H), 7,33 (t,J=7,3, 1H), 3,47 (s, 2H), 2.95 and (t,J=6,1, 2H), 2,78 (t,J=9,6, 2H), 2,45 to 2.35 (m, 2H), 2.13 in (s, 1H), 2,05-of 1.95 (m, 2H), 1.93 and is 1.70 (m, 4H), 1,59 (l,J=10,9, 2H), to 1.38 (s, 9H), 1,20-of 1.05 (m, 2H).

Example 285

The dihydrochloride {1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 266, step C. Mass spectrum (ESI): mass calculated for C25H30N4About2S; 450,2; m/z found 451,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,78-8,55 (m, 4H), of 7.97 (d,J=8,1, 1H), 7,78 (l,J=8,6, 3H), 7,71 (l,J=7,8, 1H), 7,45 (t,J=8,5, 1H), was 7.36 (t,J=7,1, 1H), 4,32 (s, 2H), 3,20 was 3.05 (m, 2H), 3.00 and-to 2.85 (m, 2H), 2,472 (l,J=4,7, 2H), 2,62-of 2.50 (m, 2H), 2,65-to 2.42 (m, 2H), 2,38-2,05 (m, 1H), 2,02 is 1.70 (m, 6H), 1,68 of 1.50 (s, 2H).

Example 286

2-(4-pyrrolidin-1 ylmethylene)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using pyrrolidine. Mass spectrum (ESI): mass calculated for C18H18N2OS; 310,1; m/z found 311,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l, =9,0, 1H), of 7.70 (d,J=8,0, 1H), of 7.48-7,37 (m, 5H), 7,33 (t,J=7,7, 1H), 3,62 (s, 2H), 2,49-to 2.40 (m, 4H), 1,78-of 1.65 (m, 4H).

Example 287

2-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}ethanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using 2-ethylaminoethanol. Mass spectrum (ESI): mass calculated for C18H20N2About2S; 328,1; m/z found 329,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,0, 1H), of 7.70 (d,J=7,7, 1H), 7,50 was 7.36 (m, 5H), 7,33 (t,J=7,7, 1H), 4,39 (t,J=5,4, 1H), 3,63 (s, 2H), 3,49 (kV,J=6,4, 2H), 2.57 m at 2.45 (m, 4H), and 1.00 (t,J=7,1, 3H).

Example 288

2-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-2-yl}ethanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using 2-piperidine-2-retinol. Mass spectrum (ESI): mass calculated for C21H24N2About2S; 368,2; m/z found 369,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): to 7.93 (d,J=8,0, 1H), of 7.70 (d,J=7,7, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t,J=6,9, 1H), 4,42 (s, 1H), 3,92 (l,J=14,0, 1H), 3,50 (Sirs, 2H), and 3.31 (d,J=6,4, 1H), 2,70-2,60 (m, 1H), 2,14-2,03 (m, 1H), 1,87 is 1.75 (m, 1H), 1.70 to 1.55V (m, 3H), 1,53-of 1.27 (m, 5H).

Example 289

1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}alanon

is shown in the title compound was obtained in accordance with the methodology described in example 259, step D using 1-piperazine-1-ratanana. Mass spectrum (ESI): mass calculated for C20H21N3About2S; 367,1; m/z found 368,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,0, 1H), of 7.70 (d,J=to 7.5, 1H), of 7.48-7,39 (m, 5H), 7,33 (t,J=7,7, 1H), 3,55 (s, 2H), 3,50 is 3.40 (m, 4H), 2.40 a (t,J=4,9, 2H), 2,33 (t,J=5,0, 2H), 1,99 (s, 3H).

Example 290

8-[4-(benzothiazol-2-yloxy)benzyl]-2,8-diaza-Spiro[4.5]Decan-1-he

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using 2,8-diaza-Spiro[4.5]Decan-1-it. Mass spectrum (ESI): mass calculated for C22H23N3About2S; 393,2; m/z found 394,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,4, 1H), of 7.70 (d,J=8,0, 1H), 7,54 (s, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t,J=8,2, 1H), 3,51 (s, 2H), 3.15 in (t,J=6,8, 2H), 2,75(l,J=11,6, 2H), 2.05 is (t,J=10,0, 2H), 1.91 a (t,J=6,8, 2H), 1.70 to (t,J=12,6, 2H), 1,33 (l,J=12,8, 2H).

Example 291

Spiro[isobenzofuran-1(3H),4'-piperidine]-3-one, 1'-[4-benzothiazol-2-yloxy)benzyl]

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using Spiro[isobenzofuran-1(3H),4'-piperidine]-3-one. Mass spectrum (ESI): mass calculated for C26H22N2About3 S; 442,1; m/z found 443,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.95 (d,J=7,9, 1H), 7,83 (l,J=7,6, 1H), 7,82-7,76 (m, 2H), of 7.70 (d,J=8,0, 1H), to 7.61 (t,J=7,8, 1H), 7,56-of 7.48 (m, 2H), 7,47-7,40 (m, 3H), 7,33 (t,J=7,4, 1H), 3,66 (s, 2H), 2,90 (l,J=11,1, 2H), 2,41 (t,J=11,0, 2H), 2,28 (t,J=13,3, 2H), 1,66 (l,J=12,6, 2H).

Example 292

(R)-1-[4-(benzothiazol-2-yloxy)benzyl]pyrrolidin-3-ol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using (R)pyrrolidin-3-ol. Mass spectrum (ESI): mass calculated for C18H18N2About2S; to 326.1; m/z found 327,2 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,0, 1H), of 7.70 (d,J=8,1, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t,J=7,2, 1H), 4.72 in (q,J=4,5, 1H), 4,27-4,16 (m, 1H), 3,60 (kV,J=13,2, 2H), 2,73-to 2.65 (m, 1H), 2,60 (kV,J=8,1, 1H), 2,47-of 2.38 (m, 1H), 2,36-of 2.30 (m, 1H), 2,07-of 1.95 (m, 1H), 1,62 of 1.50 (m, 1H).

Example 293

2-[4-(2-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using 2-methylpiperidine. Mass spectrum (ESI): mass calculated for C20H22N2OS; 338,2; m/z found 339,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=8,0, 1H), of 7.70 (d,J=8,1, 1H), 7,30-7,33 (m, 5H), 7,33 (t,J=7,9, 1H), 3.96 points (l,J=13,9, 1H, 3,19 (l,J=13,9, 1H), 2,70-2,60 (m, 1H), 2.40 a-2,30 (m, 1H), 1,98 (t,J=13,0, 1H), 1,68-of 1.56 (m, 2H), 1,54 is 1.34 (m, 2H), 1.32 to 1,24 (m, 2H), 1,11 (l,J=6,2, 3H).

Example 294

[4-(benzothiazol-2-yloxy)benzyl]diethylamin

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using diethylamine. Mass spectrum (ESI): mass calculated for C18H20N2OS; 312,1; m/z found 313,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,9, 1H), of 7.70 (d,J=8,0, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t,J=7,2, 1H), only 3.57 (s, 2H), 2,48 (kV,J=7,1, 4H), and 1.00 (t,J=7,1, 6H).

Example 295

[4-(benzothiazol-2-yloxy)benzyl}butylmethylamine

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using butylmethylamine. Mass spectrum (ESI): mass calculated for C19H22N2OS; 326,2; m/z found 327,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,9, 1H), of 7.70 (d,J=to 7.5, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t,J=8,0, 1H), 3,49 (s, 2H), 2,34 (t,J=7,1, 2H), 2.13 and (s, 3H), 1,50-of 1.40 (m, 2H), 1,38-1,24 (m, 2H), 0.88 to (t,J=7,3, 3H).

Example 296

2-{1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-yl}ethanol

Specified in the title compound was obtained in accordance with the methodology described is Oh in example 259, stage D, using 2-piperidine-2-retinol. Mass spectrum (ESI): mass calculated for C21H24N2About2S; 368,2; m/z found 369,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,74 (l,J=7,9, 1H), 7,49 (l,J=8,0, 1H), 7,30-7,16 (m, 5H), 7,13 (t,J=7,9, 1H), 4,13 (t,J=5,1, 1H), 3.27 to (s, 2H), 3,23 (kV,J=6,2, 2H), 2,59 (l,J=11,1, 2H), 1,72(t,J=10,3, 2H), 1,42 (l,J=12,1, 2H), 1,16 (t,J=3,8, 3H), 1.00 m-0,85 (m, 2H).

Example 297

1-[4-(benzothiazol-2-yloxy)benzyl}piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using piperidine-4-ol. Mass spectrum (ESI): mass calculated for C19H20N2About2S; 340,1; m/z found 341,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,9, 1H), 7.68 per (e,J=8,0, 1H), 7,46 and 7.36 (m, 5H), 7,32 (t,J=8,1, 1H), 4,60 (l,J=4,9, 1H), to 3.58 is 3.40 (m,3H), 2,80 (l,J=9,9, 1H), 2,65 (l,J=10,7, 1H), 1,87 (t,J=9,2, 1H), 1,80 (l,J=8,6, 1H), 1,71 (t,J=9,8, 1H), 1,62 (l,J=13,3, 1H), 1,48-to 1.38 (m, 1H), 1,12-1,00 (m, 1H).

Example 298

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-2-yl}methanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using piperidine-2-ylmethanol. Mass spectrum (ESI): mass calculated for C20H22N2About2 S; 354,1; m/z found 355,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,98 (l,J=7,2, 1H), 7,74 (l,J=8,0, 1H), 7,53-7,42 (m, 5H), 7,37 (t,J=8,3, 1H), 4,60 (t,J=5,2, 1H), 4,18 (l,J=14,1, 1H), 3.75 to the 3.65 (m, 1H), 3,56-of 3.46 (m, 1H), 3,37 (l,J=3,8, 1H), 2,72 (l,J=11,9, 1H), 2,36 (l,J=4,8, 1H), 2,07 (t,J=9,7, 1H), 1,72 (t,J=13,2, 2H), 1,58-of 1.26 (m, 4H).

Example 299

(R)-{1-[4-(benzothiazol-2-yloxy)benzyl]pyrrolidin-2-yl}methanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using (R)pyrrolidin-2-ylmethanol. Mass spectrum (ESI): mass calculated for C19H20N2About2S; 340,1; m/z found 340,1 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.97 (d,J=7,2,1H), 7,73 (l,J=7,8, 1H), 7,50-7,38 (m, 5H), was 7.36 (t,J=7,9, 1H), 4,90 (t,J=5,4, 1H), 4,14 (l,J=13,4, 1H), 3,55-of 3.48 (m, 1H), 3,42 (l,J=13,4, 2H), 2,84 (t,J=6,6, 1H), 2,68-of 2.58 (m, 1H), 2,20 (kV,J=8,6, 1H), 1,95 of-1.83 (m, 1H), 1,72-of 1.55 (m, 3H).

Example 300

2-(4-azetidin-1 ylmethylene)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using azetidine. Mass spectrum (ESI): mass calculated for C17H16N2About2S; 296,1; m/z found 297,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,80 (l,J=8,5, 1H), 7,56 (l,J=8,0, 1H), and 7.3-7,24 (m, 5H), 7,19 (t,J=7,3, 1H), 3.43 points (s, 2H), to 3.02 (t,J=7,0, 4H), 1,92 and 1.80 (m, 2H).

Example 301

1-[4-(benzothiazol-2-yloxy)benzyl]-[1,4]diazepan-5-he

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D using [1,4]diazepan-5-it. Mass spectrum (ESI): mass calculated for C19H19N3About2S; 353,1; m/z found 354,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,94 (l,J=7,9, 1H), 7,69 (l,J=7,9, 1H), EUR 7.57 (t,J=5,4, 1H), 7,44-7,33 (m, 5H), 7,33 (t,J=8,2, 1H), 3,62 (s, 2H), 3,18-3,10 (m, 2H), 2,58-to 2.40 (m, 6H).

Example 302

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-3-yl}methanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using piperidine-3-ylmethanol. Mass spectrum (ESI): mass calculated for C20H22N2About2S; 354,1; m/z found 355,3 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,98 (l,J=7,2, 1H), 774 (l,J=7,9, 1H), 7,50-7,42 (m, 5H), 7,38 (t,J=8,2, 1H), 4,46 (t,J=5,3, 1H), 3,52 (l,J=3,4, 2H), 3,36 be 3.29 (m, 1H), 3.27 to 3,18 (m, 1H), 2,92 (l,J=8,1, 1H), 2,77 (l,J=10,8, 1H), 1,96 (l,J=12,8, 1H), 1,75-to 1.60 (m, 4H), 1,58-of 1.45 (m, 1H), 1.00 m-0,85 (m, 1H).

Example 303

Amide 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-3-carboxylic acid

The decree of the TES in the title compound was obtained in accordance with the methodology described in example 259, step D, using amide piperidine-3-carboxylic acid. Mass spectrum (ESI): mass calculated for C20H21N3About2S; 367,1; m/z found 368,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): of 7.70 (d,J=7,8, 1H), 7,46 (l,J=8,0, 1H), 7,25-7,00 (m, 7H), 6,53 (s, 1 H), 3,26 (l,J=2,9, 2H), 2.57 m (e,J=10,3, 1H), 2.49 USD (D.,J=11,3, 1H), 2,15-2,00 (m, 1H), 1,78 (t,J=10,7, 1H), 1.69 in (t,J=9,4, 1H)and 1.51 (d,J=10,0, 1H), 1,40 (l,J=12,9, 1H), 1,22 (kV,J=12,6, 1H), 1,09 (kV,J=12,2, 1H).

Example 304

Tert-butyl ester 9-[4-(benzothiazol-2-yloxy)benzyl]-3,9-diaza-Spiro[5.5]undecane-3-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using tert-butyl ether 3,9-diaza-Spiro[5.5]undecane-3-carboxylic acid. Mass spectrum (ESI): mass calculated for C28H35N3About3S; 493,2; m/z found of 494.5 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,13 (l,J=7,9, 1H), 7,89 (l,J=8,0, 1H), 7.68 per-7,56 (m, 5H), 7,53 (t,J=7,1, 1H), 3,70 (s, 2H), 3,51 is-3.45 (m, 4H), 2,60-of 2.50 (m, 4H), of 1.66 (t,J=5,3, 4H), was 1.58 (s, 9H), and 1.54 (t,J=5,4, 4H).

Example 305

2-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-3-yl}ethanol

Specified in the title compound was obtained in accordance with the procedure described in example 259, step D, using the-W 2-piperidine-3-retinol. Mass spectrum (ESI): mass calculated for C21H24N2About2S; 368,2; m/z found 369,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 7,71 (l,J=8,4, 1H), 7,47 (l,J=7,9, 1H), 7,25-to 7.15 (m, 5H), 7,10 (t,J=8,1, 1H), 4,12 (t,J=5,1, 1H), 3.33 and is 3.15 (m, 4H), 2,58-to 2.42 (m, 2H), 1,67 (t,J=9,6, 1H), 1,53-of 1.33 (m, 4H), of 1.30 to 1.00 (m, 3H), 0.70 to EUR 0.58 (m, 1H).

Example 306

Triftoratsetata salt of CIS-4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step B, using CIS-4-aminocyclohexanecarboxylic acid. Mass spectrum (ESI): mass calculated for C22H24N2About3S; 396,2; m/z found 397,3 [M+H]+.1H NMR (400 MHz, CDCl3): 9,15, (s, 1H), of 7.75 (d,J=7,6, 1H), 7,72 (DD,J=8,0, 0,7, 1H), 7,43 (dt,J=7,2, 1,2, 1H), 7,37-7,29 (m, 5H), 5,10 (Sirs, 1H), 3,29 (Sirs, 2H), 3,10 (t,J=7,4, 3H), 2,73 (Sirs, 1H), 2,24 (shirt,J=10,6, 2H), 2,09 (shirt,J=9,3, 2H), 1,72-of 1.52 (m,3H).

Example 307

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon

A. Bis-triftorbyenzola 2-[4-(2-piperazine-1-retil)phenoxy]benzothiazole.

Tert-butyl ether 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-carboxylic acid was obtained in accordance with the methodology, is written in example 262, stage b, using tert-butyl ether piperazine-1-carboxylic acid. A solution of tert-butyl ester 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-carboxylic acid (3.9 g, 8.9 mmol) in CH2Cl2(5 ml) and a solution of 50% triftormetilfullerenov acid in CH2Cl2(35 ml) was stirred at 23°C for 4 h the Reaction mixture was concentrated, the residue is suspended in diethyl ether, filtered and dried to obtain specified in the connection header in the form of a solid white color (5,4 g, yield 94%). Mass spectrum (ESI): exact mass calculated for C19H21N3About1S1; 339,1; m/z found 340,4 [M+H]+.1H NMR (400 MHz, D6-DMSO): 9,50-of 9.30 (width, s, 1H), 7,94 (DD,J=7,9, 0,6, 1H), 7.68 per (e,J=7,6 Hz, 1H), of 7.48-7,41 (m, 5H), 7,39-7,30 (m, 1H), 4,15-3,50 (Sirs, 1H), 3.45 points-of 3.32 (m, 8H), 3,32-3,20 (m, 2H), 3,01 (DD,J=8,8, 5,2 Hz, 2H).

C. (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon.

Specified in the title compound was obtained in accordance with the procedure described in example 257, step C, using tetrahydrofuran-2-carboxylic acid and triethylamine. Mass spectrum (ESI): exact mass calculated for C24H27N3About3S; 437,2; m/z found 438,5 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=7,3, 1H), 7,71 (DD,J=7,8, 0,8, 1H), 7,42 (dt,J=7,3, 1,2, 1H), 7,33-7,26 (m, 5H)and 4.65 (DD,J =7,0, 5,3, 1H), 3,99 (DDD,J=7,7, 7,1, 6,7, 1H), 3,92-3,86 (m, 1H), 3,82-and 3.72 (m, 2H), 3,76 (s, 1H), 3,70-to 3.58 (m, 2H), 2,90 (DD,J=10,3, 7,3, 2H), 2,70 (DD,J=8,6, 5,6, 2H), 2,64-of 2.54 (m, 3H), 2,38-of 2.28 (m, 1H), 2,14-1,90 (m, 4H).

Example 308

(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amide propane-2-sulfonic acid

A solution of amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid (example 22, 197 mg, 0.5 mmol) in THF (5 ml) was treated with Pan (14 mg, 0.6 mmol) and isopropylacetanilide (86 mg, 0.6 mmol) and the reaction mixture was stirred at 60°C for 16 hours, the Reaction mixture was cooled, the reaction was suppressed by the addition of CH3HE (5 ml), then H2O (5 ml) and the pH was brought to 7. The solution was extracted with ethyl acetate (2×25 ml) and an ethyl acetate solution washed with 1M Paon (2×30 ml). United alkaline leaching was neutralized by addition of 2M HCl and was extracted with chloroform (2×30 ml). Solutions of chloroform was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified on SIO, SIS2(4 g; 0-10% 2M NH3/CH3HE:CH2Cl2) obtaining specified in the title compound as a solid (45 mg, yield 18%). Mass spectrum (ESI): exact mass calculated for C24H28N3About5S2; 503,2; m/z found 504,5 [M+H]+.1H NMR (400 MHz, C6D6 ): to 7.77 (d,J=7,8, 1H), 7,20 (DD,J=8,0, 0,8, 1H), 7,16-7,10 (m, 2H), 7,07 (dt,J=8,3, 1,0, 1H), 6.90 to (dt,J=8,0, 1,0, 1H), 6,76 (l,J=8,8, 1H), 6,13 (s, 1H), 3,98 (Sirs, 2H), 3,51 (cept,J=6,8, 2H), 3,20 (Sirs, 2H), 2,82 (Sirs, 1H), 2,37 is 2.00 (m, 4H), 1,96-of 1.84 (m, 2H), 1,33 (l,J=6,6, 6H) 1,38 of 1.28 (m, 2H).

Example 309

Methyl ester of (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid

A solution of bis-triftoratsetata 2-[4-(2-piperazine-1-retil)phenoxy]benzothiazole (296 mg, 0.52 mmol) in CH2Cl2(3 ml) was treated with triethylamine (0.25 ml, 1.8 mmol)was then added methylchlorosilanes (of 0.07 ml, 0.8 mmol) and the reaction mixture was stirred at 23°C for 20 minutes. The reaction mixture was diluted with CH2Cl2(10 ml) and washed with saturated aqueous Panso3(10 ml). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to obtain specified in the title compound (234 mg, yield 99%). Mass spectrum (ESI): exact mass calculated for C22H23N3About4S; 425,1; m/z found 426,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=7,6, 0,5, 1H), of 7.70 (d,J=7,8, 1H), 7,41 (dt,J=7,3, 1,0, 1H), 7,34-7,26 (m, 5H), 3,91 (s, 3H), and 3.72 (t,J=4,8, 2H), 3,51 (t,J=4,8, 2H), 2,86, (DD,J=10, 6,8, 2H), 2,70, (DD,J=8,6, 5,6, 2H), 2,62-to 2.57 (m, 4H).

Example 310

Cryptomaterial the more salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)benzosulfimide

Specified in the title compound was obtained in accordance with the procedure described in example 34, step B, using benzosulfimide. Mass spectrum (ESI): exact mass calculated for C27H27N3About4S2; 521,1; m/z found 522,3 [M+H]+.1H NMR (400 MHz, CD3OD): 8,60-of 8.00 (m, 2H), 7,82-7,76 (m, 1H), 7,73-EUR 7.57 (m, 4H), of 7.48-7,28 (m, 5H), 3,70 (Sirs, 1H), 3,41-to 3.34 (m, 2H), 3,14 are 2.98 (m, 3H), 2,60 (Sirs, 1H), 2,08 (shirt,J=13,6, 2H), 1,86 (Sirs, 2H) 1,30 (Sirs, 2H), 0,94-0,88 (m, 2H).

Example 311

Triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)methanesulfonamide

Specified in the title compound was obtained in accordance with the procedure described in example 34, step B, using methanesulfonamide. Mass spectrum (ESI): exact mass calculated for C22H25N3About4S2; 459,1; m/z found 460,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,81 (l,J=7,8, 1H), 7.62mm (l,J=8,1, 1H) 7,49-the 7.43 (m, 3H), 7,43-7,38 (m, 2H), 7,34 (t,J=7,8, 1H), 3,80 (shirt,J=10,4, 1H), 3,48 is 3.40 (m, 2H), 3.33 and (s, 3H), of 3.28 (s, 2H), 3,20 totaling 3.04 (m, 3H), 2,70-2,60 (m, 1H), 2,21 (shirt,J=12,4, 2H), 2.06 to of 1.93 (m, 2H).

Example 312

Triftoratsetata salt (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid

Specified in the title compound was obtained in accordance with the tvii with methods described in example 253, step D. Mass spectrum (ESI): exact mass calculated for C21H21N3About4S; 411,1; m/z found 412,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,75 (t,J=8,3, 2H), of 7.70 (dt,J=8,0, 0,8, 1H), 7,28-7,22 (m, 5H), 4,28-3,88 (SIRM, 4H), to 3.58-3,20 (SIRM, 6H), and 3.16-3.04 from (SIRM, 2H).

Example 313

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)morpholine-4-ylmethanol

A solution of bis-triftoratsetata 2-[4-(2-piperazine-1-retil)phenoxy]benzothiazole example 307, stage And (268 mg, 0.47 mmol) in CH2Cl2(6 ml) was treated with PS-dimethylamino resin (1.3 g, 0.90 mmol), then 4-morpholinylcarbonyl (of 0.07 ml, 0.6 mmol) and the reaction mixture was stirred for 1 hour. The reaction mixture was treated with PS-isocyanate resin to remove excess isocyanate and, after 15 minutes, the reaction mixture was filtered and concentrated, obtaining mentioned in the title compound (225 mg, yield 99%). Mass spectrum (ESI): exact mass calculated for C24H28N4About3S1; 452,2; m/z found 453,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,0, 0,5, 1H), 7,71 (DD,J=7,8, 0,5, 1H), 7,42 (dt,J=7,3, 1,2, 1H), 7,34-7,28 (m, 5H), 3,78-3,70 (m, 4H), 3,39 (shirt,J=4,3, 4H), and 3.31 (t,J=4,8, 4H), 2,90 (DD,J=10,4, 7,3, 2H), 2,70 (DD,J=8,3, 7,3, 2H), 2,59 (Sirs, 4H).

Example 314

1-(4-{2-[4-(b shall societal-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-thiophene-2-ylatason

Specified in the title compound was obtained in accordance with the procedure described in example 313 using 2-thiophenated. Mass spectrum (ESI): exact mass calculated for C25H25N3About3S2; 463,1; m/z found rub464.3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,0, 0,5, 1H), 7,71 (DD,J=7,8, 0,8, 1H), 7,43 (dt,J=7,3, 1,2, 1H), 7,34-7,28 (m, 5H), 7,25 (DD,J=5,3, 1,2, 1H), 7,00 (DD,J=5,0, 3,2, 1H), of 6.96-6,93 (m, 1H), 3.96 points (l,J=0,8, 2H), 3,74 (t,J=4,8, 2H)and 3.59 (t,J=4,8, 2H), 2,86 (DD,J=10,4, 7,6, 2H), 2,66 (DD,J=8,3, 5,6, 2H), by 2.55 (t,J=5,3, 2H), 2,47 (t, J=5,0, 2H).

Example 315

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-3-ylmethanol

Specified in the title compound was obtained in accordance with the procedure described in example 313 using the hydrochloride of 2-nicotinoid. Mass spectrum (ESI): exact mass calculated for C25H24N4About2S; 444,2; m/z found 445,4 [M+H]+.1H NMR (400 MHz, CDCl3): 8,73-to 8.70 (m, 2H), 7,81 (dt,J=7,9, 1,9, 1H), to 7.77 (DD,J=8,1, 0,5, 1H), 7,71 (DDD,J=7,9, 0,7, 0,4, 1H), 7,45-7,39 (m, 2H), 7,34-7,28 (m, 5H), 3,90 (Sirs, 2H), 3,52 (Sirs, 2H), 2,92-to 2.85 (m, 2H), 2,71 (DD,J=8,9, 5,6, 2H), 2,74-2,60 (m, 2H), 2,54 (Sirs, 2H).

Example 316

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)cyclopropylmethanol

Specified in the title compound which was lucali in accordance with the methodology described in example 313 using cyclopropanecarbonitrile. Mass spectrum (ESI): exact mass calculated for C23H25N3About2S; 407,2; m/z found 408,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,71 (DD,J=7,9, 0,8, 1H), 7,43 (dt,J=7,4, 1,3, 1H), 7,34-7,28 (m, 5H), 3,74 (l,J=16,0, 4H), 2,89 (DD,J=9,4, 6,5, 2H), 2,70 (DD,J=9,4, 6,5, 2H), 2,58 (shirt,J=20,8, 4H), 1,78 (TT,J=8,0, 4,7, 1H), 1.06 a-a 1.01 (m, 2H), 0,83-0,78 (m, 2H).

Example 317

1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-methoxyethanol

A solution of bis-triftoratsetata 2-[4-(2-piperazine-1-retil)phenoxy]benzothiazole example 307, step A (200 mg, 0.35 mmol) in CHCl3(14 ml) was treated with PS-dimethylamino resin (740 mg, 1.0 mmol) and the reaction mixture was stirred for 1 hour. Then the resin was filtered, the resulting solution of the free base was treated methoxybutanol acid (0.04 ml, 0.5 mmol) and PS-carbonyldiimidazole resin (500 mg, 0.6 mmol) and the reaction mixture was stirred for 1 hour. The reaction mixture was filtered, concentrated and the crude product was purified on SIO, SIS2(12 g, 0-10% 2M NH3/Meon:CH2Cl2), getting mentioned in the title compound (143 mg, yield 99%). Mass spectrum (ESI): exact mass calculated for C22H25N3About2S; 411,2; m/z found 412,4 [M+H]+.sup> 1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,6, 1H), 7,71 (DD,J=7,9, 0,8, 1H), 7,42 (dt,J=7,5, 1,3, 1H), 7,35-7,28 (m, 5H), 4,14 (s, 2H), and 3.72 (t,J=4,8, 2H), to 3.58 (t,J=4,8, 2H), 3,47 (s, 3H), 2,89 (DD,J=10,6, 7,3, 2H), 2,70 (DD,J=8,5, 5,6, 2H), 2,58 (t,J=5,1, 4H).

Example 318

1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2,2,2-triptoreline

Specified in the title compound was obtained in accordance with the procedure described in example 317 using triftormetilfullerenov acid. Mass spectrum (ESI): exact mass calculated for C21H20F3N3O2S; 435,1; m/z found 436,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,2, 0,5, 1H), 7,71 (DD,J=7,9, 0,7, 1H), 7,43 (dt,J=8,5, 1,2, 1H), 7,35-7,28 (m, 5H), 4,14 (s, 2H), 3,76 (t,J=4,8, 2H), 3,68 (t,J=4,7, 2H), 2,88 (DD,J=10,0, 7,0, 2H), 2,70 (DD,J=8,7, 5,6, 2H), 2,62 (t,J=4,6, 4H).

Example 319

4-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-carbonyl)benzoic acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using nanometrology ester of terephthalic acid and in example 250, step D. Mass spectrum (ESI): exact mass calculated for C27H25N3O4S; 487,2; m/z found 488,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 8,00 (l,J=83, 2H), to 7.93 (DD,J=8,0, 0,8, 1H), 7,69 (DD,J=8,0, 0,4, 1H), 7,50 (d,J=8,3, 2H), 7,43 (dt,J=7,5, 1,3, 1H), 7,40-7,29 (m, 5H), 3,66 (Sirs, 2H), 3,30 (Sirs, 2H), 2,88 (DD,J=7,0, 7,0, 2H), 2,60 (DD,J=8,3, 8,3, 2H), 2,55 (Sirs, 2H), 2,44 (Sirs, 2H).

Example 320

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-4-ylmethanol

Specified in the title compound was obtained in accordance with the procedure described in example 317 using isonicotinic acid. Mass spectrum (ESI): exact mass calculated for C25H24N4O2S; 444,2; m/z found 445,4 [M+H]+.1H NMR (400 MHz, CDCl3): a total of 8.74 (DD,J=4,4, 1,6, 1H), to 7.77 (DD,J=8,1, 0,5, 1H), 7,71 (DD,J=7,9, 0,8, 1H), 7,43 (dt,J=7,4, 1,3, 1H), 7,45-7,39 (m, 2H), 7,35-7,28 (m, 7H), a 3.87 (Sirs, 2H), 3,44 (shirt,J=3,9, 2H), 2,88 (DD,J=10,1, 6,9, 2H), 2,71 (DD,J=8,8, 5,5, 2H), 2,70-of 2.64 (m, 2H), 2,54-2,49 (m, 2H).

Example 321

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(5-methylpyrazine-2-yl)methanon

Specified in the title compound was obtained in accordance with the procedure described in example 317 using 5-methylpyrazine-2-carboxylic acid. Mass spectrum (ESI): exact mass calculated for C25H25N5O2S; 444,2; m/z found 445,4 [M+H]+.1H NMR (400 MHz, CDCl3): 8,89 (l,J=1,4, 1H), 8,45 (l,J=1,0, 1H), 7,76 (DD,J=8,1, 0,5, 1H), of 7.70 (DD,J=8,0, 0,8, 1H), 7,43(dt, J=7,4, 1,3, 1H), 7,33-7,28 (m, 5H), 3,90 (shirt,J=4,7, 2H), of 3.77 (shirt,J=4,8, 2H), 2,92 (DD,J=10,5, 6,5, 2H), 2,80-of 2.72 (m, 2H), 2,69-of 2.64 (m, 2H), 2,66 (s, 3H).

Example 322

(R)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon

Specified in the title compound was obtained in accordance with the procedure described in example 317 using 5-(R)-tetrahydrofuran-2-carboxylic acid. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S; 437,2; m/z found 438,5 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=7,3, 1H), 7,71 (DD,J=7,8, 0,8, 1H), 7,42 (dt,J=7,3, 1,2, 1H), 7,33-7,26 (m, 5H)and 4.65 (DD,J=7,0, 5,3, 1H), 3,99 (DDD,J=7,1, 6,7, 6,7, 1H), 3,92-3,86 (m, 1H), 3,82-and 3.72 (m, 2H), 3,76(with,1H), 3,70-to 3.58 (m, 2H), 2,90 (DD,J=10,3, 7,3, 2H), 2,70 (DD,J=8,6, 5,6, 2H), 2,64-of 2.54 (m, 3H), 2,38-of 2.28 (m, 1H), 2,14-1,90 (m, 4H).

Example 323

(S)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon

Specified in the title compound was obtained in accordance with the procedure described in example 317 using 5-(S)-tetrahydrofuran-2-carboxylic acid. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S; 437,2; m/z found 438,5 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=7,3, 1H), 7,71 (DD,J=7,8, 0,8, 1H), 7,42 (dt,J=7,3, 1,2, 1H), 7,33-7,26 (m, 5H), 465 (DD, J=7,0, 5,3, 1H), 3,99 (DDD,J=7,1, 6,7, 6,7, 1H), 3,89 (DDD,J=7,7, 7,5, 5,8, 1H), 3,82-and 3.72 (m, 2H), 3,76(with,1H), 3,70-to 3.58 (m, 2H), 2,90 (DD,J=10,3, 7,3, 2H), 2,70 (DD,J=8,6, 5,6, 2H), 2,64-of 2.54 (m, 3H), 2,38-of 2.28 (m, 1H), 2,14-1,90 (m, 4H).

Example 324

(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-3-yl)methanon

Specified in the title compound was obtained in accordance with the procedure described in example 317 using 5-tetrahydrofuran-3-carboxylic acid. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S; 437,2; m/z found 438,5 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,71 (DD,J=7,9, 0,8, 1H), 7,42 (dt,J=7,5, 1,3, 1H), 7,33-7,26 (m, 5H), 4,06 (t,J=8,2, 1H), 3,97-a 3.87 (m, 3H), of 3.77-to 3.67 (m, 2H)and 3.59 (t,J=5,1, 1H), 3,35-3,24 (m, 1H), 2,88 (DD,J=10,2, 7,3, 2H), and 2.79 (DD,J=8,5, 5,7, 2H), 2,60-of 2.50 (m, 4H), 2,29 (dddd,J=12,6, 7,6, 6,4, 6,4, 1H), 2,17-of 2.08 (m, 1H).

Example 325

1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-hydroxyethane

Specified in the title compound was obtained in accordance with the procedure described in example 317 using glycolic acid. Mass spectrum (ESI): exact mass calculated for C21H23N3O3S; 397,2; m/z found 398,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,71 (DD,J=8,0, 0,7, 1H), 7,43 (dt,J=7,5, 1,, 1H), 7,35-7,28 (m, 5H), is 4.21 (s, 2H, in), 3.75 (t,J=5,0, 2H), 3,68 (Sirs, 1H), 3,35 (t,J=5,0, 2H), 2,88 (DD,J=10,1, 7,0, 2H), 2,70 (DD,J=8,6, 5,6, 2H), 2,58 (DDD,J=8,4, 8,3, 5,2, 1H).

Example 326

2-[2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-oxoethyl]Cyclopentanone

Specified in the title compound was obtained in accordance with the procedure described in example 317 using 5-(2-oxocyclopent)acetic acid. Mass spectrum (ESI): exact mass calculated for C26H29N3O3S; 463,2; m/z found 464,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (d,J=7,7, 1H), 7,71 (DD,J=7,9, 0,7, 1H), 7,42 (dt,J=7,5, 1,2, 1H), 7,33-7,28 (m, 5H), 3,80-to 3.64 (m, 2H), 3,54 (DD,J=9,2, 3,9, 1H), 2,92-2,84 (m, 3H), 2,88 (DD,J=10,1, 7,0, 2H), 2,68 (DD,J=8,5, 5,6, 2H), 2,60 was 2.25 (m, 2H), 2,15-to 2.06 (m, 1H), 1.93 and-of 1.80 (m, 1H), 1,78-of 1.64 (m, 2H).

Example 327

Triftoratsetata salt of 3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)propionic acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using 3-piperazine-1-ylpropionic acid. Mass spectrum (ESI): exact mass calculated for C21H23N3O3S1; 411,2; m/z found 412,4 [M+H]+.1H NMR (400 MHz, CDCl3): 11,25 (Sirs, 1H), 7,76 (DD,J=8,0, 0,5, 1H), 7,69 (DD,J=7,8, 0,6, 1H), 7,42 (dt,J/i> =7,4, 1,2, 1H), 7,35-7,28 (m, 5H), 3,76 (s, 1H), 3.04 from (t,J=6,4, 4H), 2.91 in (DD,J=10,3, 5,4, 4H), 2,86-and 2.79 (m, 2H), 2.63 in (t,J=6,4, 1H), 2,08 (s, 4H).

Example 328

3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)oxazolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it, and in example 259, step A. Mass spectrum (ESI): exact mass calculated for C23H25N3O3S1; 423,2; m/z found 424,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,69 (DD,J=7,9, 1,1, 1H), 7,41 (dt,J=8,5, 1,2, 1H), 7,35-7,28 (m, 5H), 4,36, (t,J=7,8, 2H), and 3.72 (t,J=4,8, 2H), 3,86 is 3.76 (m, 1H), 3,57 (t,J=8,1, 2H), 3,11 (shirt,J=11,8, 2H), 2,86 (DD,J=11,0, 7,6, 2H), 2,66 (DD,J=8,6, 5,2, 2H), 2,18 (dt,J=11,7, 2,7, 2H), 1,89-1,72 (m, 4H).

Example 329

4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)morpholine-3-one

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using piperidine-4-Immortalis-3-one, and in example 260, step A. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S1; 437,2; m/z found 438,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=8,0, 1H), of 7.70 (DD,J=7,9, 0,7, 1H), 7,42 (the t, J=7,4, 1,2, 1H), 7,33-7,28 (m, 5H), 4,57 (TT,J=11,9, 4,3, 1H), 4,23 (s, 2H), 3,91, (t,J=4,9, 2H), 3,34 (t,J=5,1, 2H), 3,12 (shirt,J=11,6, 2H), 2,87 (DD,J=10,9, 7,6, 2H), to 2.67 (DD,J=8,7, 5,2, 2H), 2,23 (DDD,J=11,7, 11,6, 2,5, 2H), equal to 1.82 (DDD,J=24,1, 12,1, 3,8, 2H), 1,76 is 1.70 (m, 2H).

Example 330

4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)morpholine-3-one

Specified in the title compound was obtained in accordance with the procedure described in example 17, step A, using piperidine-4-Immortalis-3-one, and in example 260, step A. Mass spectrum (ESI): exact mass calculated for C24H27N3O4S1; 453,2; m/z found 454,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (DD,J=8,1, 0,5, 1H), 7,68 (DD,J=7,9, 0,7, 1H), 7,40 (dt,J=7,4, 1,3, 1H), 7,31-7,28 (m, 3H), 7,02-of 6.96 (m, 2H), 4,57 (TT,J=12,1, 4,2, 1H), 4,22 (s, 2H), 4,14 (t,J=5,6, 2H), 3,90 (t,J=5,0, 2H), 3.33 and (t,J=5,1, 2H), 3,12 (shirt,J=11,7, 2H), 2,87 (t,J=5,7, 2H), 2,32 (DDD,J=11,8, 11,8, 2,4, 2H), 1,82 (dddd,J=12,2, 12,1, 12,1, 3,8, 2H), 1,75 by 1.68 (m, 2H).

Example 331

3-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)oxazolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 17, step A, using cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it, and in example 259, step A. Mass spectrum (ESI): exact mass calculated the La 23H25N3O4S1; 439,2; m/z found 440,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (DD,J=8,1, 0,7, 1H), 7,69 (DD,J=8,0, 0,7, 1H), 7,42 (dt,J=8,6, 1,3, 1H), 7,35-7,26 (m, 3H), 7,02-6,97 (m, 2H), 4,36 (DD,J=8,7, 7,3, 2H), 4,14 (t,J=5,7, 2H), 3,80 (DDD,J=16,4, 11,0, 5,6, 1H), 3,60-of 3.53 (m, 2H), 3,12 (shirt,J=12,0, 2H), 2,87 (l,J=5,7, 2H), 2,28 (DDD,J=11,7, 11,6, 3,8, 2H), 1,90-of 1.74 (m, 4H).

Example 332

Benzylacetone 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

A solution of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid example 34, stage (383 mg, 1.0 mmol) in CH2Cl2(10 ml) was treated with N-methylmorpholine (of 0.24 ml, 2.2 mmol) and acid chloride cyanuric acid (61 mg, 0.3 mmol), the resulting solution was stirred for 1 hour, then the reaction mixture was treated with O-benzylhydroxylamine and was stirred for 16 hours, the Reaction mixture was filtered through a layer of diatomaceous earth, concentrated and purified on SIO, SIS2(12 g, 0-10% 2M NH3/Meon:CH2Cl2), getting mentioned in the title compound (81 mg, yield 17%). Mass spectrum (ESI): exact mass calculated for C28H29N3About3S1; 487,2; m/z found 488,5 [M+H]+.1H NMR (400 MHz, CDCl3): a 8.34 (Sirs, 1H), 7,76 (DD,J=8,1, 0,5, 1H), of 7.70 (DD,J=7,9, 0,7, 1H), 7,45-7,39 (m, 6H), 7,34-7,28 (m, 4H), 4,96 (Sirs, 2H), 3,05 (shirt,J=11,6, 2H) 2,85 (DD, J=10,6, 7,6, 2H), 2.63 in (DD,J=8,5, 5,5, 2H), 2,04 (DDD,J=11,0, 11,0, 2,8, 2H), 1,91 to 1.76 (m, 2H).

Example 333

(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using ethyl ether piperidine-4-luxusni acid in example 250, step D. Mass spectrum (ESI): exact mass calculated for C22H24N2O3S1; 396,2; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CD3OD): a 8.34 (Sirs, 1H), 7,82 (DD,J=7,9, 0,6, 1H), to 7.67 (DD,J=8,1, 0,5, 1H), 7,53-7,33 (m, 6H), 3,78-3,66 (m, 2H), 3.46 in-to 3.38 (m, 2H), 3,22-3,14 (m, 2H), 3,14-of 3.07 (m, 2H), 2,39 (shirt,J=6,1, 1H), 2,20-2,08 (Sirs, 1H), 2,11 (shirt,J=13,5, 1H), 1,72-and 1.54 (m, 2H).

Example 334

(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using the acetate salt of (R)-4-hydroxy-1-piperidine-4-iparralde-2-it, and in example 261, step A. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S1; 437,2; m/z found 438,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,66 (DD,J=7,9, 0,7, 1H), 7,40 (dt,J=7,7, 1,3, 1H), 7,28-of 7.24 (m, 5H), to 4.52 (DDD,J=8,5, 5,9, 2,4, 1H), 4,11-4,00 (m, 1H), 3,60 (DD,J=10,7, 5,6, 1H), and 3.31 (DD,J=10,7, 2,2, 1H), 3,12 totaling 3.04 (m, 2H), and 2.83 (DD,J=9,7, 6,5, 2H), 2,72 (DD,J=17,2, 6,6, 1H), 2.63 in (DD,J=9,8, 6,4, 2H), 2,72 (DD,J=17,2, 2,6, 1H), 2.21 are a 2.12 (m, 2H), 1.85 to to 1.67 (m, 4H).

Example 335

Hydroxyamide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using hydroxyamide piperidine-4-carboxylic acid. Mass spectrum (ESI): exact mass calculated for C21H23N3O3S1; 397,2; m/z found 398,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73-of 7.60 (m, 2H), 7,40-7,30 (m, 1H), 7,30-7,16 (m, 5H), 3,48-3,36 (Sirs, 2H), 3,10-2,95 (m, 4H), 2,80-2,50 (SIRM, 3H), 2.23 to-1,96 (SIRM, 5H).

Example 336

(S)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using the acetate salt of (S)-4-hydroxy-1-piperidine-4-iparralde-2-it, and in example 261, step A, using (S)-4-bromo-3-hydroxybutyrate. Mass spectrum (ESI): exact mass calculated for C24H27N3O3S1; 437,2; m/z found 438,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.77 (DD,J=8,1, 0,5, 1H), 7,66 (DD,J =7,9, 0,7, 1H), 7,40 (dt,J=7,7, 1,3, 1H), 7,28-of 7.24 (m, 5H), to 4.52 (DDD,J=8,5, 5,9, 2,4, 1H), 4,11-4,00 (m, 1H), 3,60 (DD,J=10,7, 5,6, 1H), and 3.31 (DD,J=10,7, 2,2, 1H), 3,12 totaling 3.04 (m, 2H), and 2.83 (DD,J=9,7, 6,5, 2H), 2,72 (DD,J=17,2, 6,6, 1H), 2.63 in (DD,J=9,8, 6,4, 2H), 2,72 (DD,J=17,2, 2,6, 1H), 2.21 are a 2.12 (m, 2H), 1.85 to to 1.67 (m, 4H).

Example 337

Tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using tert-butyl ether piperidine-4-ylcarbamate acid. Mass spectrum (ESI): exact mass calculated for C25H31N3O3S1; 453,2; m/z found 454,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,2, 0,6, 1H), 7,65 (DD,J=7, 9, 0,7, 1H), 7,39 (dt,J=7,4, 1,3, 1H), 7,29-of 7.23 (m, 5H), 4,47 (shirt,J=6,6, 1H), 3,55 is-3.45 (m, 1H), 2,93 (shirt,J=11,3, 2H), 2,82 (DD,J=11,0, 7,7, 2H), 2,60 (DD,J=8,6, 5,3, 2H), 2,16 (t,J=11,3, 2H), 1,97 (shirt,J=11,1, 2H), 1,45 (s, 9H).

Example 338

2-{4-[2-(4-foreperiod-1-yl)ethyl]phenoxy}benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using 4-foreveryday. Mass spectrum (ESI): exact mass calculated for C20H21F1N3O1S1; 356,1; m/z found 357,3 [M+H +.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,1, 0,5, 1H), 7,65 (DD,J=8,0, 0,7, 1H), 7,41 and 7.36 (m, 1H), 7,28-of 7.24 (m, 5H), 4,70 (DM,J=48,6, 1H), 2,85 (DD,J=10,9, 7,7, 2H), 2.71 to 2,63 (m, 2H), 2,62 (DD,J=8,3, 5,4, 2H), 2,52 is 2.44 (m, 2H), 2,03 is 1.86 (m, 4H).

Example 339

2-{4-[2-(4,4-deformability-1-yl)ethyl]phenoxy}benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using 4,4-deformability. Mass spectrum (ESI): exact mass calculated for C20H20F2N3O1S1; 374,1; m/z found 375,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,1, 0,6, 1H), 7,65 (DD,J=8,0, 0,7, 1H), 7,41 and 7.36 (m, 1H), 7,28-of 7.24 (m, 5H), 2,82 (DD,J=10,2, 6,4, 2H), 2.71 to 2,60 (m, 6H), 2,09-of 1.97 (m, 4H).

Example 340

(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}pyrrolidin-3-ol

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using (R)-3-hydroxypyrrolidine. Mass spectrum (ESI): exact mass calculated for C19H20N2O2S1; 340,1; m/z found 341,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,0, 0,4, 1H), 7,66 (DD,J=7,9, 0,8, 1H), 7,39 (dt,J=7,4, 1,2, 1H), 7,31-of 7.24 (m, 5H), 4,36 (dddd,J=7,3, 4,8, 2,2, 2,2, 1H), 2,96 (DDD,J=8.5 a, 8.5 a, 5,1, 1H), 2,90-and 2.83 (m, 2H), 2,79-2,70 (m, 3H), 2,58 (DD,J=10,0, 5,2, 2H), a 2.36 (DDD, J=8,8, 8,8, 6,5, 1H), 2,21 (dddd,J=13,7, 8,6, 7,2, 5,1, 1H), 1,82-of 1.73 (m, 1H).

Example 341

N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)formamide

Specified in the title compound was obtained from the compound of example 337 in accordance with the methods described in example 266, step In, and in example 317. Mass spectrum (ESI): exact mass calculated for C21H23N3O2S1; 381,2; m/z found 382,4 [M+H]+.1H NMR (400 MHz, CDCl3): 8,16 (s, 1H), 7,72 (l,J=8,6, 1H), 7,65 (DD,J=7,9, 0,7, 1H), 7,42 and 7.36 (m, 1H), 7,31-of 7.23 (m, 5H), a 4.03-3,93 (m, 1H), 3,13-3,03 (m, 2H), 2,90 (DD,J=11,1, 7,2, 2H), 2,75-2,69 (m, 2H), 2,34 (t,J=9,2, 2H), 2,08 is 2.00 (m, 2H), 1,72 is 1.60 (m, 2H).

Example 342

(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)urea

Hydrochloride of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine was obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid of example 337 in accordance with the procedure described in example 266, step C. the resulting amine hydrochloride (227 mg, of 0.58 mmol) in CH2Cl2(5 ml) was treated with pyridine (of 0.14 ml, 1.7 mmol), trimethylsilane (and 0.09 ml, 0.64 mmol) and triethylamine (0,08 ml of 0.58 mmol) and the reaction mixture was stirred for 16 hours the Reaction mixture was diluted with CH2Cl2(25 ml) and washed Na the CO 3(30 ml). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified on SIO, SIS2(12 g, 0-10% [2M NH3] CH3HE/CH2Cl2) obtaining specified in the title compound (134 mg, yield 58%). Mass spectrum (ESI): exact mass calculated for C21H24N4About2S1; 396,2; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,7, 1H), 7,65 (DD,J=7,9, 0,7, 1H), 7,42 and 7.36 (m, 1H), 7,31-of 7.23 (m, 5H), is 4.93 (d,J=8,0, 1H), 4,78 (s, 2H), 3,93 (shirt,J=11,7, 1H), 2,82 (DD,J=10,7, 7,6, 2H), 2,60 (DD,J=8,5, 5,4, 2H), 2,16 (t,J=11,3, 2H), 1,97 (DD,J=12,7, 3,1, 2H), 1,47 (dddd,J=12,8, 12,6, 12,6, 3,7, 2H).

Example 343

1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-phenylazomethine

Hydrochloride of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine was obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid of example 337 by removal of the BOC-group in accordance with the procedure described in example 266, step C. the Free base was obtained by suspendirovanie hydrochloride 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine (1.3 g, 3.3 mmol) in CH2Cl2(20 ml) and washing with saturated solution Panso3(20 ml). The organic layer was dried over Na2SO , filtered and concentrated under reduced pressure to obtain 1.0 g (yield 83%) of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-iluminado free base. A solution of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine (145 mg, 0.4 mmol) in ethanol (5 ml) was treated with diphenylcyanoarsine (319 mg, of 1.34 mmol) and was heated up to 80°C for 16 hours the Reaction mixture was concentrated under reduced pressure and was purified on SIO, SIS2(12 g, 0-10% [2M NH3] CH3HE/CH2Cl2) obtaining specified in the title compound (173 mg, yield 85%). Mass spectrum (ESI): exact mass calculated for C28H27N5About2S1; 496,2; m/z found 498,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,7, 1H), 7,66 (DD,J=7,9, 0,7, 1H), 7,45 was 7.36 (m, 4H), 7,31-of 7.24 (m, 5H), was 7.08 (d,J=7,8, 2H), 6,36 (shirt,J=6,5, 1H), a 3.87 is 3.76 (m, 1H), 3,02 (shirt,J=11,2, 2H), and 2.83 (DD,J=8,4, 7,3, 2H), 2,64 (DD,J=8,6, 5,4, 2H), 2,21 (t,J=11,1, 2H), 2,07 (l,J=11,0, 2H), 1,76 (DD,J=20,7, 10,4, 2H).

Example 344

1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylisothiazoline

Hydrochloride of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine was obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid of example 337 by removal of the BOC-group in accordance with the methods is Oh, described in example 266, step C. the Free base was obtained as described in example 343. A solution of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine (145 mg, 0.4 mmol) in ethanol (5 ml) was treated with dimethyl-N-cyanodithioiminocarbonate (180 mg, of 1.34 mmol) and was heated up to 80°C for 16 hours the Reaction mixture was concentrated under reduced pressure and was purified on SIO, SIS2(12 g, 0-10% 2M NH3/CH3HE/CH2Cl2) obtaining specified in the title compound (143 mg, yield 69%). Mass spectrum (ESI): exact mass calculated for C23H25N5About1S2; 451,2; m/z found 452,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,1, 0,5, 1H), 7,66 (DD,J=7,9, 0,7, 1H), 7,41 and 7.36 (m, 2H), 7,29-of 7.24 (m, 5H), 6,13 (shirt,J=196, 2H), 2,97 (shirt,J=12,0, 2H), 2,82 (DD,J=10,3, 7,3, 2H), 2,62 (DD,J=8,5, 5,5, 2H), 2,60-2,44 (Sirs, 3H), 2,18 (t,J=11,5, 2H), 2,03 (l,J=13,5, 2H), 1,7-of 1.55 (m, 2H).

Example 345

N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methanesulfonamide

Hydrochloride of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine was obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid of example 337 by removal of the BOC-group in accordance with the procedure described in example 266, step C. the Free base was obtained as described in example 343. Free the warping (240 mg, of 0.68 mmol) in CH2Cl2(7 ml) was treated with triethylamine (142 μl, 1.0 mmol), then methanesulfonanilide (77 μl, 1.0 mmol) and the solution was stirred for 16 hours the Reaction mixture was diluted with CH2Cl2(20 ml) and washed with a solution Panso3(30 ml). The organic layer was dried, concentrated under reduced pressure and then purified on SIO, SIS2(12 g, 0-10% 2M NH3/CH3HE:CH2Cl2)to give 168 mg (yield 57%) specified in the connection header. Mass spectrum (ESI): exact mass calculated for C21H25N3About3S2; 431,1; m/z found 432,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,65 (DD,J=7,9, 0,7, 1H), 7,42 and 7.36 (m, 1H), 7,29-of 7.24 (m, 5H), of 4.45 (d,J=7,6, 1H), 3,42-of 3.31 (m, 1H), 2,99 (s, 3H), 2,93 (shirt,J=12,0, 2H), 2,81 (DD,J=10,6, 7,5, 2H), 2,60 (DD,J=8,5, 5,4, 2H), 2,18 (t,J=11,0, 2H), 2,02 (l,J=12,5, 2H), 1,47 (dddd,J=11,2, 11,1, 11,1, 3,7, 2H).

Example 346

1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylguanine

A solution of 1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-phenylazomethine example 343 (76 mg, 0.15 mmol) in ethanol (3 ml) was treated with a solution of 40% methylamine in water (0.2 ml) and the solution was stirred at 80°C for 1 hour. The reaction mixture was cooled to 23°C and concentrated under reduced pressure to get crude is solid substances, which was purified on SIO, SIS2(4 g; 0-10% 2M NH3/CH3HE:CH2Cl2), receiving 50 mg (yield 76%) specified in the connection header. Mass spectrum (ESI): exact mass calculated for C23H26N6About1S1; 434,2; m/z found 435,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), to 7.67 (DD,J=7,9, 0,7, 1H), 7,42 and 7.36 (m, 2H), 7,29-of 7.24 (m, 5H), 5,67 (Sirs, 1H), 4.75 in (Sirs, 1H), 3,63 (Sirs, 1H), 2,94 (shirt,J=11,9, 2H), 2,86 (l,J=4,9, 2H), 2,82 (DD,J=10,4, 7,4, 2H), 2,61 (DD,J=8,5, 5,5, 2H), 2,18 (t,J=11,4, 2H), 2.05 is is 1.96 (m, 2H), 2,61 (dddd,J=12,3, 12,3, 12,3, 3,6, 2H).

Example 347

8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1-phenyl-1,3,8-triaza-Spiro[4.5]Decan-4-one

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using 1-phenyl-1,3,8-triaza-Spiro[4.5]decane-2,4-it. Mass spectrum (ESI): exact mass calculated for C28H28N4About2S1; 484,2; m/z found 485,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (DD,J=8,0, 0,5, 1H), 7,66 (DD,J=7,9, 0,7, 1H), 7,52 (s, 1H), 7,42 and 7.36 (m, 1H), 7,34-7,24 (m, 6H), 6,91 (l,J=8,0, 1H), 6.87 in (t,J=7,3, 1H), and 4.75 (s, 2H), 2.95 and-to 2.85 (m, 4H), was 2.76-of 2.66 (m, 4H), 1,76 (l,J=13,9, 2H).

Example 348

8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-triaza-Spiro[4.5]decane-2,4-dione

Specified in the title compound was obtained according to the accordance with the methodology described in example 262, step A, using 1,3,8-triaza-Spiro[5.5]decane-2,4-dione. Mass spectrum (ESI): exact mass calculated for C22H22N4About3S1; 422,1; m/z found 423,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,1, 0,5, 1H), to 7.67 (DD,J=7,9, 1,1, 1H), 7,42 and 7.36 (m, 1H), 7,34-of 7.24 (m, 5H), 3,0 (DDD,J=of 9.2, 4.3, 4,3, 2H), 2,86 (DD,J=10,6, 6,9, 2H), 2,69 (DD,J=9,0, 5,3, 2H), 2,72 (t,J=10,2, 2H), 2,19 is 2.10 (m, 2H), 1.75 of (l,J=13,6, 2H).

Example 349

Tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamate acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using tert-butyl ester methylpiperidin-4-ylcarbamate acid. Mass spectrum (ESI): exact mass calculated for C26H23N3About3S1: 467,2; m/z found 468,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,1, 0,5, 1H), 7,66 (DD,J=7,9, 0,7, 1H), 7,41 and 7.36 (m, 1H), 7,29-7,25 (m, 5H), 4,10-3,95 (SIRM, 1H), 3,07 (l,J=11,6, 2H), and 2.83 (DD,J=11,1, 7,8, 2H), 2,75 (s, 3H), 2,61 (l,J=8,6, 5,2, 2H), 2,11 (t,J=10,9, 2H), 2,19 is 2.10 (m, 2H), 1.77 in (dddd,J=12,1, 12,0, 12,0, 3,3, 2H), 1.70 to of 1.64 (m, 2H), 1,47 (s, 9H).

Example 350

N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylacetamide

Specified in the header of the connection is received and the connection 349 in accordance with the methodology described in example 266, step b In example 343 and example 345, using acetylchloride. Mass spectrum (ESI): exact mass calculated for C23H27N3About2S1, 409,2; m/z found 410,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,1, 0,6, 1H), 7,66 (DD,J=8,0, 1,1, 1H), 7,41 and 7.36 (m, 1H), 7,31-7,25 (m, 5H), 4,53 (TT,J=12,0, 4,2, 0,5H), 3,54 (TT,J=11,7, 4,0, 0,5H), 3.15 and totaling 3.04 (m, 2H), 2,90-2,78 (m, 5H), 2,70-of 2.58 (m, 2H), 2,24-to 2.06 (m, 5H), 2.00 in a 1.96 (m, 1H), 1,82 is 1.60 (m, 3H).

Example 351

N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylmethanesulfonamide

Specified in the title compound was obtained from the compound of example 349 in accordance with the procedure described in example 266, step b In example 343 in example 345, using methanesulfonanilide. Mass spectrum (ESI): exact mass calculated for C25H29N3About4S; 467,2; m/z found 468,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (DD,J=7,9, 0,7, 1H), 7,42 and 7.36 (m, 1H), 7,29-of 7.24 (m, 5H), 3,78 (TT,J=11,9, 4,2, 1H), is 3.08 (DD,J=9,6, 2,1, 1H), 2,84 (s, 3H), 2,82 (s, 3H), 2,83-and 2.79 (m, 2H), 2,61 (DD,J=8,5, 5,3, 2H), 2,18 (DDD,J=11,8, 11,8, 2,2, 2H), 1,86 (dddd,J=12,2, 12,0, 12,0, 3,4, 2H), 1,76 was 1.69 (m, 2H).

Example 352

[(1-{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamoyl]methyl ester acetic acid

Specified in the header connect the s was obtained from the compound of example 349 in accordance with the methodology described in example 266, step b In example 343 in example 345, using chlorocarbonate ester of acetic acid. Mass spectrum (ESI): exact mass calculated for C23H27N3About2S1; 467,2; m/z found 468,4 [M+H]+.1H NMR (400 MHz, CDbl3): 7,73 (DD,J=8,1, 0,5, 1H), 7,66 (l,J=7,9, 1H), 7,42 and 7.36 (m, 1H), 7,29-of 7.24 (m, 5H), was 4.76 (s, 0,6H), 4,71 (s, 1,4H), 4,48 (TT,J=12,0, 4,3, 0,7H), 3,36 (TT,J=11,6, 4,4, 0,3H), 3,16 totaling 3.04 (m, 2H), 2,90-2,78 (m, 5H), 2,68-of 2.58 (m, 2H), 2,19 (s, 3H), 2,19-2,05 (m, 2H), 2,01-of 1.84 (m, 1H), 1,82 is 1.60 (m, 3H).

Example 353

N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-ndimethylacetamide

Specified in the title compound was obtained from the compound of example 337 in accordance with the procedure described in example 266, step b In example 343 in example 345, using acetylchloride. Mass spectrum (ESI): exact mass calculated for C25H29N3About4S; 395,2; m/z found 396,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,66 (DD,J=7,9, 0,6, 1H), 7,42 and 7.36 (m, 1H), 7,29-of 7.24 (m, 5H), 5,48 (l,J=7,8, 1H), a 3.87-of 3.77 (m, 1H), 2,95 (DD,J=11,6, 2H), and 2.83 (DD,J=10,8, 7,6, 2H), 2,62 (DD,J=8,5, 5,3, 2H), 2,18 (l,J=11,4, 2H), 2.00 in was 1.94 (m, 2H), up to 1.98 (m, 2H), 1,49 (dddd,J=12,3, 12,2, 12,2, 3,6, 2H).

Example 354

(1-{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbonyl]methyl ester acetic acid

The decree of the TES in the title compound was obtained from the compound of example 337 in accordance with the methodology described in example 266, step b In example 343 in example 354, using chlorocarbonate ester of acetic acid. Mass spectrum (ESI): exact mass calculated for C24H27N3About4S; 453,2; m/z found of 454.3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (DD,J=8,2, 0,6, 1H), to 7.67 (DD,J=7,9, 0,7, 1H), 7,42 and 7.36 (m, 1H), 7,29-of 7.24 (m, 5H), equal to 6.05 (d,J=8,0, 1H), of 4.54 (s, 2H), 3.96 points-of 3.85 (m, 1H), 3.00 and (l,J=8,2, 0,6, 2H), 2,85 (DD,J=10,6, 7,4, 2H), 2,85 (DD,J=10,6, 7,4, 2H), 2,66 (DD,J=8,6, 5,3, 2H), 2,23 (t,J=11,4, 2H), 2,18 (s, 3H), 1,98 (l,J=9,7, 2H), 1.57 in (dddd,J=12,4, 12,4, 12,3, 3,6, 2H).

Example 355

(S)-2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)-3-(1H-imidazol-2-yl)propionic acid

Specified in the title compound was obtained in accordance with the procedure described in example 262, step A, using (S)-3-(1H-imidazol-2-yl)-2-methylaminopropane acid. Mass spectrum (ESI): exact mass calculated for C22H22N4About3S1: 422,1; m/z found 423,3 [M+H]+.1H NMR (400 MHz, CD3OD): cent to 8.85 (s, 1H), 7,81 (DD,J=7,9, 0,6, 1H), 7,72 (DD,J=8,1, 0,5, 1H), 7,58-7,42 (m, 4H), 7,39-7,34 (m, 3H), 4,34, (DD,J=9,3, 4,9, 3H), 3,71-3,42, (m, 4H), 3,35-of 3.32 (m, 2H), 3,20 (l,J=8,6, 2H), is 3.08 (s, 3H).

Example 356

2-(4-{2-[4-(3-nitropyridine-2-yl)-[1,4]diazepan-1-yl]ethyl}phenoxy)benzothiazole

Specified in the header connection p which were given in accordance with the methodology described in example 262, step A, using 1-(3-nitropyridine-2-yl)-[1,4]diazepan. Mass spectrum (ESI): exact mass calculated for C25H25N2About3S1: 457,2; m/z found 476,1 [M+H]+.1H NMR (400 MHz, CDCl3): at 8.36 (DD,J=4,5, and 1.7, 1H), 8,14 (DD,J=8,1, 1,7, 1H), to 7.77 (DD,J=8,1, 0,5, 1H), of 7.70 (DD,J=8,0, 0,7, 1H), 7,45-7,40 (m, 1H), 7,29-of 7.24 (m, 5H), was 6.73 (DD,J=8,0, 4,4, 1H), 3,80-3,75 (Sirs, 2H), 3,47-3,40 (Sirs, 2H), 3,07-3,01 (Sirs, 2H), 2.95 and-is 2.88 (m, 2H), 2,86-and 2.79 (m, 4H), 2,20-2,10 (Sirs, 2H).

Example 357

2-(4-piperidine-1-ylmethylene)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 251, step B, using piperidine. Mass spectrum (ESI): mass calculated for C19H20N2OS: 324,4; m/z found 325,3 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.75 (d,J=8,2, 1H), 7,73 (l,J=8,2, 1H), was 7.36-7,42 (m, 3H), 7.24 to to 7.32 (m, 3H), 3,49 (s, 2H), 2,39 (Sirs, 3H), 1.56 to of 1.64 (m, 5H), of 1.40 to 1.48 (m, 2H).

Example 358

1-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 251, step B, using 4-phenylpiperidine-4-ol. Mass spectrum (ESI): mass calculated for C25H24N2About3S, 416,5; m/z found 417,4 [M+H]+.1H NMR (400 MHz, CDCl3):of 7.75 (d, J=8,0, 1H), 7,66 (l,J=8,0, 1H), 7,55-7,51 (m, 2H), 7,47-7,25 (m, 9H), 3,63 (s, 2H), 2,85-2,77 (m, 2H), 2,50 (dt,J=11,8, 2,5, 2H), 2,18 (dt,J=13,0, 4,4, 2H), 1,80-of 1.74 (m, 2H), 1.55V (Sirs, 1H).

Example 359

1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol

Specified in the title compound was obtained in accordance with the procedure described in example 251, step B, using 4-piperidinol. Mass spectrum (ESI): mass calculated for C19H20N2About3S, 340,4; m/z found 341,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,32-7,24 (m, 3H), 3,68-to 3.64 (m, 1H), 3.46 in (s, 2H), 2,81 was 2.25 (m, 2H), 2,20-of 2.15 (m, 2H), 1,95-1,90 (m, 2H), 1,67 is 1.58 (m, 3H).

Example 360

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol

Specified in the title compound was obtained in accordance with the procedure described in example 251, step B, using piperidine-4-ylmethanol. Mass spectrum (ESI): mass calculated for C20H22N2About2S, 354.5 TWh excluding; m/z found 355,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42-7,37 (m, 3H), 7,32-7,25 (m, 3H), of 3.54 (s, 2H), 3,51 (l,J=6,5, 2H), 2,97-2,90 (m, 2H), 2,01 (dt,J=11,6, 2,4, 3H), 1,73 (l,J=12,1,2H), 1,58 to 1.47 (m, 1H), 1,37-of 1.26 (m, 2H).

Example 361

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}metasolv name

Specified in the title compound was obtained in accordance with the procedure described in example 253, stages a and b, and then example 258, step C. Mass spectrum (ESI): mass calculated for C20H23N3About3S2, 417,6; m/z found 418,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), 7.68 per (e,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,35-7,25 (m, 3H), 4,32 to 4.5 (m, 1H), to 3.58 (s, 2H), 3.43 points-of 3.32 (m, 1H), 2,99 (s, 3H), 2,87 is 2.80 (m, 2H), 2,18 is 2.10 (m, 2H), 2,04 is 1.96 (m, 2H), 1,64-and 1.54 (m, 2H).

Example 362

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido

Specified in the title compound was obtained in accordance with the method described in example 258, stages a and b, and then in example 253, step C, using glycolic acid. Mass spectrum (ESI): mass calculated for C22H26N3About3S, 411,5; m/z found 412,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,2, 1H), to 7.67 (d,J=8,2, 1H), 7,42-7,37 (m, 3H), 7,32-7,25 (m, 3H), 4,11 (s, 2H), 3,51 (s, 2H), 3,24 (t,J=6,3, 2H), 2,88-to 2.94 (m, 2H), 2,20 (l,J=11,5, 1H), 2,02-of 1.92 (m, 2H), 1,72-of 1.65 (m, 2H), 1,62 of 1.50 (m, 2H), 1,36-of 1.26 (m, 2H).

Example 363

Methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, stages a and b, and then example 258, tadia With, using methyl isocyanate. Mass spectrum (ESI): mass calculated for C21H23N3About3S, 397,5; m/z found 398,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,32-7,24 (m, 3H), 4,57 (Sirs, 1H), 3,66 (s, 3H), 3,51 (s, 2H), 2,85-and 2.79 (m, 2H), 2,18-of 2.09 (m, 2H), 1,98-1,90 (m, 2H), 1,51-of 1.40 (m, 2H).

Example 364

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea

Specified in the title compound was obtained in accordance with the method described in example 258, phase a, b and C, using trimethylsilyltriflate. Mass spectrum (ESI): mass calculated for C21H24N4About2S, 396,5; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,32-7,24 (m, 3H), with 4.64 (Sirs, 1H), 4,35 (s, 2H), 3,50 (s, 2H), 3,07 (shirt,J=6,3, 2H), 2,94-is 2.88 (m, 2H), 1,86 is 2.01 (m, 2H), 1,72-of 1.66 (m, 2H), 1.56 to the 1.44 (s, 1H), 1,24-of 1.23 (m, 2H).

Example 365

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-triptorelin

Specified in the title compound was obtained in accordance with the method described in example 258, stages a and b in example 257, step C, using triperoxonane acid. Mass spectrum (ESI): mass calculated for C22H22F3N3O2S, 449,5; m/z found 450,4 [M+H]+.1 H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,32-7,24 (m, 3H), 6,41 (Sirs, 1H), 3,51 (s, 2H), 3,28 (t,J=6,46, 2H), 2,92 (l,J=11,5, 2H), 2,02-of 1.94 (m, 2H), 1,74-and 1.54 (m, 3H), 1,38-of 1.27 (m, 2H).

Example 366

{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 259, stage C and D, and in example 250, step D, using piperazine-1-luxusni acid. Mass spectrum (ESI): mass calculated for C20H21N3O3S, 383,5; m/z found 384,4 [M+H]+.1H NMR (400 MHz, CD3OD): to 7.77 (d,J=8,0, 1H), 7.62mm (l,J=8,0, 1H), 7,50-7,46 (m, 2H), 7,42-7,26 (m, 4H), to 6.67 (s, 2H), 3,60 (s, 2H), 3,34 (Sirs, 4H), 2,77 (Sirs, 4H).

Example 367

2-[4-(4-methanesulfonylaminoethyl-1-ylmethyl)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 257, stages a and b in example 258, step C. Mass spectrum (ESI): mass calculated for C19H21N3O3S2, 403,53; m/z found 404,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), 7.68 per (e,J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,35-7,26 (m, 3H), of 3.57 (s, 2H), 3,26 (shirt,J=4,7, 4H), and 2.79 (s, 3H), 2,58 (shirt,J=4,7, 4H).

Example 368

1-{4-[4-(benzothiazol-2-yloxy)is ensil]piperazine-1-yl}-2,2,2-triptoreline

Specified in the title compound was obtained in accordance with the procedure described in example 257, phase a, b and C, using triperoxonane acid. Mass spectrum (ESI): mass calculated for C20H18F3N3O2S, 421,44; m/z found 422,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), 7.68 per (e,J=8,0, 1H), 7,42-7,27 (m, 6H), 3,74-3,70 (m, 2H), 3,65-of 3.60 (m, 2H), only 3.57 (s, 2H), 2,56-of 2.50 (m, 4H).

Example 369

2-(4-(morpholine-4-ylmethylene)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 259, stage C and D, using the research. Mass spectrum (ESI): mass calculated for C18H18N2O2S, 326,42; m/z found 327,4 [M+H]+.1H NMR (500 MHz, CDCl3): 7,74 (l,J=7,7, 1H), to 7.67 (d,J=7,7, 1H), 7,42-7,37 (m, 3H), 7,33-7,25 (m, 3H), and 3.72 (t,J=3,7, 4H), 3,52 (s, 2H), 2,46 (Sirs, 4H).

Example 370

Phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, stages a and b, and then example 258, step C, using phenylisocyanate. Mass spectrum (ESI): mass calculated for C28H25N3About3S, 459,57; m/z found 460,4 [M+H]+.1H NMR (400 MHz, CDl 3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,42-7,10 (m, 11H), 4,95 (shirt,J=7,8, 1H), 3,67-to 3.58 (m, 1H), 3,53 (s, 2H), 2,88-2,82 (m, 2H), 2.21 are to 2.06 (m, 2H), 2,03 of 1.99 (m, 2H), 1.61 of-the 1.44 (m, 2H).

Example 371

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide

Specified in the title compound was obtained in accordance with the procedure described in example 253, stages a and b, and then example 258, step C, using benzosulfimide. Mass spectrum (ESI): mass calculated for C25H25N3About3S2, 479,62; m/z found 480,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,86-to 7.84 (m, 2H), of 7.75 (d,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,60-of 7.48 (m, 3H), 7,41-7,24 (m, 6H), 4,56 (shirt,J=7,8, 1H), 3,48 (s, 2H), 3,26-and 3.16 (m, 1H), was 2.76 of 2.68 (m, 2H), 2.06 to of 1.97 (m, 2H), 1,78 is 1.70 (m, 1H), 1,52-of 1.42 (m, 2H).

Example 372

Ethyl ester of 3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid

Specified in the title compound was obtained in accordance with the procedure described in example 251, stages a and b, using ethyl ester 3-aminopropionic acid. Mass spectrum (ESI): mass calculated for C19H20N2About3S, 356,45; m/z found 357,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,0, 1H), to 7.67 (d,J=8,0, 1H), 7,44-7,25 (m, 6H), 4,21 (Sirs, 1H), 4,15 (kV,J=7,2, 2H), a 3.87 (s, 2H), 2.95 and (t,J=6,3, 2H), 2,58 (t,J=6,3, 2H), 1.26 in (t,J =7,2, 3H).

Example 373

3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid

Specified in the title compound was obtained in accordance with the procedure described in example 372, and in example 250, step D. Mass spectrum (ESI): mass calculated for C17H16N2About3S, 328,39; m/z found 329,3 [M+H]+.1H NMR (400 MHz, DMSO): 7,87 (l,J= 8,0, 1H), 7.62mm (l,J=8,0, 1H), 7,44-of 7.23 (m, 6H), of 3.77 (s, 2H), 2,72 (t,J=6,6, 2H), 2,29 (t,J=6,6, 2H).

Example 374

Ethyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 18, step A, and example 20, using the ethyl ester of 3-methylaminopropane acid. Mass spectrum (ESI): mass calculated for C26H31N3About5S, 497,62; m/z found 498,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,65 (l,J=8,0, 1H), 7,41-7,35 (m, 1H), 7,28-of 7.23 (m, 3H), 6,99-6,94 (m, 2H), 4,28-4,08 (m, 5H), of 3.12 (s, 3H), 3,10 totaling 3.04 (m, 1H), 2,98-of 2.81 (m, 4H), 2,62 of $ 2.53 (m, 1H), 2,24-2,12 (m, 2H), 1,97 of-1.83 (m, 2H), 1,81-of 1.64 (m, 2H), 1.32 to 1,24 (m, 3H).

Example 376

Ethyl ester of 1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid

Specified in the header soy is inania received in accordance with the methodology described in example 9 and example 24, using ethyl ether [1,4']bipyridinyl-4-carboxylic acid. Mass spectrum (ESI): mass calculated for C28H35N3About4S, 509,67; m/z found 510,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,0, 1H), 7,65 (l,J=8,0, 1H), 7,41-7,35 (m, 1H), 7,29-of 7.23 (m, 3H), 6,99-6,92 (m, 2H), 4,16-4,08 (m, 4H), 3,10 totaling 3.04 (m, 2H), 2,92-of 2.86 (m, 2H), 2,80 (t,J=5,9, 1H), 2,36-of 2.20 (m, 4H), 2,16-2,07 (m, 2H), 1,95-to 1.87 (m, 2H), 1,82-of 1.57 (m, 7H), 1,24 (t,J=7,0, 3H).

Example 377

1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 376 in example 250, step D. Mass spectrum (ESI): mass calculated for C26H31N3About4S, 481,62; m/z found 482,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=8,0, 1H), to 7.64 (d,J=8,0, 1H), 7,44-7,38 (m, 1H), 7,32-7,27 (m, 3H), was 7.08-7.03 is (m, 2H), 4,17 (t,J=5,4, 2H), 3,44-to 3.36 (m, 2H), 3,24-3,19 (m, 2H), 3,05-2,84 (m, 5H), 2.40 a-2,20 (m, 3H), 2,14-2,04 (m, 4H), 1,86-1,72 (m, 4H).

Example 378

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylalanine

A. {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine.

A mixture of [4-(benzothiazol-2-yloxy)phenyl]acetaldehyde (example 262, step A, 4,2 g, 15.6 mmol), cyclopropylamine (5,4 ml, 78,0 mmol) and acetic acid (4.5 ml, 78 mmol) is CH 2Cl2(156 ml) was stirred at room temperature for 1 hour. To the mixture was added Na(SLA)3(6,61 g, and 31.2 mmol). The mixture was stirred at room temperature for 24 hours, filtered through a layer of diatomaceous earth, washed with CH2Cl2(200 ml), then 1N. Paon (3×50 ml) and concentrated under reduced pressure, obtaining the crude product as a yellow oil. The crude product was purified on SIO, SIS2(330 g; 0-10% CH3HE/CH2Cl2) and received a clear oil, which crystallized upon standing (3.4 g, yield 71%). Mass spectrum (ESI): mass calculated for C18H18N2OS; 310,11; m/z found 311,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,76 (l,J=8,1, 1H),7.62mm (l,J=8,1, 1H), 7,46-7,27 (m, 6H), to 3.41 (t,J=7,6, 2H), is 3.08 (t,J=7,6, 2H), 2,38 was 2.76 (m, 1H), 0,95-0,89 (m, 4H).

Century {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylalanine.

A mixture of acetaldehyde (180 μl, 3.2 mmol), {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine (500 mg, 1.6 mmol) in CH2Cl2(32 ml) was stirred at room temperature for 1 hour. To the mixture was added Na(SLA)3(of 1.02 g, 4.8 mmol). The mixture was stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(100 ml) and concentrated under reduced pressure, obtaining the crude product in widebase yellow. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2) and received a clear oil (465 mg, yield 86%). Mass spectrum (ESI): mass calculated for C20H22N2OS; 338,15; m/z found 339,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,66 (l,J=8,1, 1H), 7,58 (l,J=8,1, 1H), 7,31 (t,J=8,1, 1H), 7.23 percent-to 7.15 (m, 5H), 2,80 (s, 4H), of 2.72 (DD,J=7,3, 7,1, 2H), 1,78 is 1.70 (m, 1H), 1,05 (t,J=7,1, 3H), 0.50 to 0,36 (m, 4H).

Example 379

Triftoratsetata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid

A. Methyl ester 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid.

To a solution of {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine (500 mg, 1.6 mmol) in CH3SP (10 ml) at room temperature was added N,N-diisopropylethylamine (349 μl, 2 mmol) and then methyl ester 3-bromo-2-methylpropionic acid (362 mg, 2 mmol). The resulting mixture was heated at 60°C over night. The mixture was cooled, dissolved in CH2Cl2(100 ml), then washed with saturated aqueous Panso3(1×25 ml) and H2O (2×25 ml), dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/THE H 2Cl2) and received light, the solid is not quite white (158 mg, yield 39%). Mass spectrum (ESI): mass calculated for C23H26N2About3S; 410,17; m/z found 411,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,73 (l,J=8,3, 1H), 7,65 (l,J=8,3, 1H), 7,38 (t,J=8,1, 1H), 7,28-of 7.23 (m, 5H), 3,66 (s, 3H), 3,01 (DD,J=8,8, 3,8, 1H), 2,89 was 2.76 (m, 5H), of 3.60 (DD,J=6,6, 6,1, 1H), 1,84-of 1.78 (m, 1H), 1,12 (l,J=7,1, 3H), 0,51-0,30 (m, 4H).

Century Triftoratsetata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid.

To a solution of methyl ester 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid (158 mg, 0.38 mmol) in a mixture of THF/CH3HE 3:1:1 (13 ml) was added a solution of lithium hydroxide (37 mg, 1.54 mmol) in H2O (3 ml). The reaction mixture was stirred at room temperature for 16 h and then concentrated under reduced pressure. The residue was dissolved in CH3HE and purified HPLC with reversed phase. The desired fractions were collected and concentrated under reduced pressure to obtain specified in the title compound as a clear oil (179 mg, yield 92%). Mass spectrum (ESI): mass calculated for C22H24N2About3S; 396,15; m/z found 397,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,78 (l,J=8,3, 1H), to 7.64 (d,J=8,1, 1H), 7,51-7,27 (m, 6H), 3,83 (t,J=12,4, 1H), 3,55 (t,J=8,1, 2H), 3,37 (l,J =13,1, 1H), 3,25 (t,J=8,8, 2H), 3,21-3,11 (m, 1H), 2,99-2,90 (m, 1H), 1,33 (l,J=7,3, 3H), 1,17 is-0.97 (m, 4H).

Example 380

2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethanol

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using cyclopropanemethylamine, and in example 379, step A, using 2-bromoethanol. Mass spectrum (ESI): mass calculated for C21H24N2About2S, 368,16; m/z found 369,3 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=8,1, 1H), 7.62mm (l,J=8,1, 1H), 7,34 (t,J=7,3, 1H), 7,27-to 7.18 (m, 5H), of 3.56 (t,J=5,3, 2H), 2,92-of 2.86 (m, 2H), 2,84-by 2.73 (m, 4H), 2.49 USD (D.,J=6,6, 2H), 0,92 is 0.81 (m, 1H), 0.55 to 0,49 (m, 2H), 0,16-0,09 (m, 2H).

Example 381

2-[2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethoxy]ethanol

Specified in the title compound was obtained in accordance with the procedure described in example 380. Mass spectrum (ESI): mass calculated for C23H28N2About3S, 412,18; m/z found 413,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.64 (d,J=8,3, 2H), 7,41 (l,J=8,3, 2H), 7,31 (t,J=8,3, 1H), 7,25-7,17 (m, 3H), 4,08 (Sirs, 1H), 3,84-3,68 (m, 6H), 3,59-to 3.49 (m, 2H), 3,26-and 3.16 (m, 2H), 1,11-0,99 (m, 1H), 0,79 to 0.70 (m, 2H), 0.55 to 0,48 (m, 2H).

Example 382

3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}qi is apropertyname)propan-1-ol

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using cyclopropanemethylamine, and in example 379, step A, using 3-bromopropane-1-ol. Mass spectrum (ESI): mass calculated for C22H26N2About2S, 382,17; m/z found 383,3 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=8,1, 1H), 7.62mm (l,J=8,1, 1H), 7,34 (t,J=8,1, 1H), 7,27-to 7.18 (m, 5H), of 3.77 (t,J=5,3, 2H), 2,84 was 2.76 (m, 6H), 2,43 (l,J=6,6, 2H), 1,72-of 1.65 (m, 2H), 0,94-0,83 (m, 1H), 0,57-0,49 (m, 2H), 0,18-0,11 (m, 2H).

Example 383

Triftoratsetata salt of {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl(3-tetrazol-2-ylpropyl)Amin

To a solution of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propan-1-ol (example 382, 220 mg of 0.58 mmol) and 2N-tetrazole (61 mg, 0.87 mmol) in CH2Cl2(12 ml) was added applied to the polymer triphenylphosphine (290 mg, 0.87 mmol) and di-tert-utilisationbased (200 mg, 0.87 mmol). The reaction mixture was stirred at room temperature for 1 h, filtered and the collected solids were washed CH2Cl2(10 ml). The filtrate was concentrated under reduced pressure and obtained crude product as a pale yellow oil. The crude product was dissolved in CH3HE and purified HPLC with reversed phase. The desired fractions from Irali and concentrated under reduced pressure to obtain specified in the title compound as a clear oil (100 mg, yield 40%). Mass spectrum (ESI): mass calculated for C23H26N6OS; 434,19; m/z found 435,3 [M+H]+.1H NMR (400 MHz, CDCl3): 8,75 (,1H), of 7.75 (d,J=8,1, 1H), 7,60 (l,J=8,1, 1H), 7,45-to 7.32 (m, 5H), 7,28 (t,J=8,1, 1H), 3,54 is 3.40 (m, 4H), 3,29-of 3.25 (m, 2H), 3,19 (l,J=7,3, 2H), 3,09 (t,J=8,6, 2H), 2,56-2,47 (m, 2H), 1,16-of 1.05 (m, 1H), 0,78 is 0.71 (m, 2H), 0,46-0,40 (m, 2H).

Example 384

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl(3-pyrrol-1-ylpropyl)Amin

Specified in the title compound was obtained in accordance with the procedure described in example 379, step A, using 1-(3-bromopropyl)-1H-pyrrole. Mass spectrum (ESI): mass calculated for C25H27N3OS, 417,19; m/z found 418,3 [M+H]+.1H NMR (400 MHz, CDCl3): the 7.65 (d,J=7,6, 1H), EUR 7.57 (d,J=8,1, 1H), 7,30 (m,J=8,1, 1H), 7,21-7,13 (m, 5H), to 6.57 (t,J=2,0, 2H), 6,07 (t,J=2,0, 2H), 3,80 (t,J=7,1, 2H), 2,80-2,69 (m, 4H), 2.57 m (t,J=7,1, 2H), 1,98-of 1.88 (m, 2H), 1,74-to 1.67 (m, 1H), 0,47-0,40 (m, 2H), 0.37 to 0.31 in (m, 2H).

Example 385

4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using cyclopropanemethylamine, and in example 319, step A, using 4-bromobutyronitrile. Mass spectrum (ESI): mass calculated for C23H25/sub> N3OS, 391,17; m/z found 392,3 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,35 (t,J=8,1, 1H), 7,27-7,20 (m, 5H), 2.77-to 2,73 (m, 4H), 2,64 (t,J=6,6, 2H), 2,39 (l,J=6,3, 2H), 2,29 (t,J=6,8, 2H), 1,74-of 1.66 (m, 2H), 0,89-0,78 (m, 1H), 0.55 to 0,48 (m, 2H), of 0.13 to 0.08 (m, 2H).

Example 386

(2-cyanoethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 33, step B, using 3-aminopropionitrile. Mass spectrum (ESI): mass calculated for C24H26N4About2S, 434,18; m/z found 435,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,3, 1H), to 7.67 (d,J=8,1, 1H), 7,40 (t,J=8,1, 1H), 7,32-of 7.24 (m, 5H), to 6.39 (t,J=6,6, 1H), 3,51(DD,J=6,3, 6,1, 2H), 3,11-3,00 (m, 2H), 2,89-2,82 (m, 2H), 2,69-of 2.58 (m, 4H), 2,23 and 2.13 (m, 1H), 2,08 (t,J=12,1, 2H), 1,94 to 1.76 (m, 4H).

Example 387

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(2H-tetrazol-5-yl)propyl]amine

To a solution of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile (example 385, 250 mg, 0.6 mmol) in toluene (32 ml) at room temperature was added trimethylaluminum (2.0m solution in toluene, of 1.53 ml, is 3.08 mmol) and then azidotimedine (404 μl, is 3.08 mmol). The resulting mixture was heated at 80°C for 18 hours the Mixture Oh what was Adali to room temperature, diluted CH2Cl2(200 ml), then washed with saturated aqueous Panso3(1×25 ml) and H2O (2×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-20% CH3HE/CH2Cl2) and received not quite white solid (246 mg, yield 88%). Mass spectrum (ESI): mass calculated for C23H26N6OS; 434,19; m/z found 435,5 [M+H]+.1H NMR (400 MHz, CDCl3): 11,25 (Sirs, 1H), 7,54 (DD,J=7,8, 5,0, 2H), 7.23 percent (DD,J=8,1, 7,3, 1H), 7,19-to 7.09 (m, 5H), 3,23-3,11 (m, 4H), 3,01-2,90 (m, 4H), 2,83 (l,J=7,3, 2H), 2,18-2,07 (m, 2H), 1,01-of 0.91 (m, 1H), 0,57-0,50 (m, 2H), 0,25-018 (m, 2H).

Example 388

3-[5-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)tetrazol-1-yl]propionitrile

To a stirred suspension of (2-cyanoethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid (example 386, 500 mg, 1.15 mmol) and triphenylphosphine (755 mg, is 2.88 mmol) in anhydrous CH3SP (10 ml) at 0°C was added diisopropylethylamine (567 μl, is 2.88 mmol), after 2 minutes, for 20 minutes was added attributively (399 μl, 3.04 from mmol). The reaction mixture was left to warm to room temperature for 30 minutes and then stirred a further 14 hours. The reaction mixture is obavljale iced water (20 ml) and was extracted with CH 2Cl2(2×25 ml). The combined organic layers were dried (Na2SO4) and concentrated. The residue was purified on SIO, SIS2(40 g; 0-15% CH3HE/CH2Cl2) and received not quite white solid (439 mg, yield 83%). Mass spectrum (ESI): mass calculated for C24H25N7OS; 459,18; m/z found 460,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,38 (t,J=7,8, 1H), 7,31-of 7.23 (m, 5H), to 4.62 (t,J=6,8, 2H), 3,20-3,10 (m, 4H), 3.04 from-to 2.94 (m, 1H), 2.91 in-2,82 (m, 2H), 2,73-of 2.64 (m, 2H), 2,25 (t,J=10,9, 2H), 2,18-2,05 (m, 2H), 2,04-of 1.95 (m, 2H).

Example 389

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl[3-(2H-tetrazol-5-yl)propyl]amine

Specified in the title compound was obtained in accordance with the procedure described in example 387. Mass spectrum (ESI): mass calculated for C20H24N6OS, 420,17; m/z found 421,5 [M+H]+.1H NMR (400 MHz, CDCl3): 13,02 (Sirs, 1H), 7,50 (DD,J=8,1, 3,5, 2H), 7,20 (m,J=8,1, 1H), 7,12? 7.04 baby mortality (m, 5H), 2.95 and-2,77 (m, 8H), 2.06 to of 1.93 (m, 3H), 0.60 and of 0.48 (m, 4H).

Example 390

(2-hydroxy-1,1-dimethylethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 33, steps In and, using 2-amino-2-methylpropan-1-ol. Mass spectrum (ESI mass, calculated for C25H31N3About3S, 453,21; m/z found 454,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.75 (d,J=8,1, 1H), 7.68 per (e,J=8,1, 1H), 7,40 (t,J=8,1, 1H), 7,32-7,25 (m, 5H), of 5.83 (s, 1H), 5,06 (Sirs, 1H)and 3.59 (s, 2H), 3,14-of 3.06 (m, 2H), 2.91 in-2,84 (m, 2H), 2,70 2.63 in (m, 2H), 2,20-2,10 (m, 3H), 1,95-of 1.74 (m, 4H), 1,32 (s, 6H).

Example 391

Triftoratsetata salt of {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(1H-[1,2,4]triazole-3-yl)propyl]amine

A. cleaners containing hydrochloride salt of the ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butylimidazole acid.

A solution of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile (example 385, 932 mg, of 2.38 mmol) in absolute ethanol (5 ml) and diethyl ether (10 ml) was barbotirovany gaseous hydrogen chloride for 1 hour. The resulting suspension was filtered and washed with ether to obtain specified in the title compound (1.12 g, yield 92%). Because of the instability, the crude product was used without purification.

Century Triftoratsetata salt of {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(1H-[1,2,4]triazole-3-yl)propyl]amine.

To a solution of cleaners containing hydrochloride salt of the ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butylimidazole acid (511 mg, 1 mmol) in ethanol (4.5 ml) EXT is ulali the triethylamine (375 μl, 2.7 mmol) and then a solution of formic acid hydrazide (60 mg, 1 mmol) in ethanol (4.5 ml). The resulting mixture was stirred at room temperature for 2 h and then boiled under reflux for 1 h the Mixture was cooled and diluted with CH2Cl2(1500 ml), then washed with saturated aqueous Panso3(1×25 ml) and H2O (2×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-15% CH3HE/CH2Cl2) and received not quite white solid (317 mg, yield 73%). Mass spectrum (ESI): mass calculated for C24H27N5OS; 433,19; m/z found 434,4 [M+H]+.1H NMR (400 MHz, CDCl3): to $ 7.91 (s, 1H), 7.68 per (e,J=7,8, 1H), 7,63 (d, J=8,1, 1H), 7,34 (t,J=8,1, 1H), 7,25-7,19 (m, 5H), 2,90 was 2.76 (m, 6H), of 2.72 (t,J=6,3, 2H), 2,46 (l,J=6,6, 2H), 2.00 in 1,90 (m, 2H), 0,93-of 0.82 (m, 1H), 0.56 to 0,49 (m, 2H), 0,16 one-0.10 (m, 2H).

Example 392

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-methyl-1H-[1,2,4]triazole-3-yl)propyl]amine

Specified in the title compound was obtained in accordance with the procedure described in example 391, the stage, using acetic acid hydrazide. Mass spectrum (ESI): mass calculated for C25H29N5OS, 447,21; m/z found 448,4 [M+H]+ 1H NMR (400 MHz, CDCl3): the 7.65 (DD,J=8,1, 8,1, 2H), 7,35 (t,J=8,1, 1H), 7,27-7,21 (m, 5H), 3,01-to 2.94 (m, 2H), 2,93-2,84 (m, 4H), of 2.81 (t,J=6,6, 2H), 2,61 (l,J=6,8, 2H), is 2.37 (s, 3H), 2,07-of 1.97 (m, 2H), 1,01-0,89 (m, 1H), 0,62-of 0.53 (m, 2H), from 0.25 to 0.17 (m, 2H).

Example 393

{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-phenyl-1H-[1,2,4]triazole-3-yl)propyl]amine

Specified in the title compound was obtained in accordance with the procedure described in example 391, the stage, using benzoic acid hydrazide. Mass spectrum (ESI): mass calculated for C30H31N5OS, 509,22; m/z found 510,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 8.06 (DD,J=16,8, 0,5, 2H), of 7.70 (d,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,42-7,30 (m, 4H), 7,28-7,20 (m, 5H), 2,99-2,87 (m, 6H), 2,85 (t,J=6,6, 2H), 2,58 (l,J=6,8, 2H), 2,09 is 2.00 (m, 2H), 1.00 and-0,89 (m, 1H), and 0.61-of 0.53 (m, 2H), of 0.23 to 0.16 (m, 2H).

Example 394

Trifurcata salt of 2-(4-{2-[4-(1-methyl-1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole

To a solution of 2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole (example 262, 80 mg, 1.97 mmol) in DMF (20 ml) was added To a2CO3(256 mg, of 1.85 mmol) and dimethylcarbonate (360 μl, 4,27 mmol). The reaction mixture was stirred at room temperature for 18 h, filtered and concentrated under reduced pressure. The crude product was dissolved in CH322H24N6OS; 420,17; m/z found 421,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,72 (l,J=7,8, 1H), 7,58 (l,J=7,8, 1H), 7,44-7,28 (m, 5H), 7,25 (t,J=8,1, 1H), 4,06 (s, 3H), 3,80 (l,J=12,1, 1H), 3,66-to 3.35 (m, 4H), 3,28-3,17 (m, 2H), 3,16-is 3.08 (m, 2H), 2,33-of 2.23 (m, 2H), 2,22-2,07 (m, 2H).

Example 395

2-(4-{2-[4-(2-methyl-2H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 394. Mass spectrum (ESI): mass calculated for C22H24N6OS, 420,17; m/z found 421,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,75 (l,J=7,8, 1H), 7,60 (l,J=7,8, 1H), 7,46-7,33 (m, 5H), 7,28 (t,J=7,8, 1H), or 4.31 (s, 3H), 3,79 (l,J=13,4, 1H), 3,62-of 3.06 (m, 8H), 2,48-of 2.30 (m, 2H), 2,15-2,02 (m, 2H).

Example 396

1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile

Specified in the title compound was obtained in accordance with the procedure described in example 262, using piperidine-4-carbonitrile. Mass spectrum (ESI): mass calculated for C21H21N3OS, 363,14; m/z found 364,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,63 (l,J =7,6, 1H), 7,55 (l,J=7,6, 1H), 7,28 (t,J=8,1, 1H), 7,20 for 7.12 (m, 5H), 2,71 (DD,J=7,1, 3,3, 2H), 2,68 is 2.55 (m, 3H), 2,52 (DD,J=7,1, 3,3, 2H), 2,37 was 2.25 (m, 2H), 1,91-of 1.73 (m, 2H).

Example 397

2-(4-{2-[4-(1H-[1,2,3]triazole-4-yl]ethyl}phenoxy)benzothiazole

To a solution of trimethylsilyldiazomethane (1.8 ml, 3.6 mmol) in diethyl ether (30 ml) at 0°C under nitrogen atmosphere was added dropwise n-utility (2.5m in hexane) (of 1.44 ml, 3.6 mmol) and the mixture was stirred at 0°C for 20 minutes. To the resulting solution was added dropwise a solution of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile (example 396, of 1.09 g, 3.0 mmol) in THF (10 ml) at 0°C. the resulting mixture was stirred at 0°C for 3 hours the Mixture was treated with saturated aqueous NH4Cl and was extracted with CH2Cl2(2×100 ml). The extracts were washed H2O (2×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2) and received not quite white solid (768 mg, yield 54%). Mass spectrum (ESI): mass calculated for C22H23N5OS; 405,16; m/z found 406,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,63 (l,J=8,1, 1H), 7,56 (l,J=8,1, 1H), 7,42 (s, 1H), 7,29 (t,J=7,8, 1H), 7.23 percent-7,14 (m, 5H), 4,67 (Sirs, 1H), 3.04 from (l,J=11,9, 2H), 2,84-2,70 (m, H), 2,63-of 2.56 (m, 2H), 2,16 (t,J=11,1, 2H), 1.97 of (l,J=12,6, 2H), 1,82 is 1.70 (m, 2H).

Example 398

Ethyl ester of 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}butyric acid

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using the ethyl ester of 4-aminobutyric acid. Mass spectrum (ESI): mass calculated for C21H24N2About3S, 384,15; m/z found 385,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,38 (t,J=8,1, 1H), 7,31-7,22 (m, 5H), 6,67 (Sirs, 1H), 4,12 (DD,J=7,3, 7,1, 2H), 2.95 and is 2.80 (m, 2H), 2,69 (t,J=6,8, 2H), 2,35 (t,J=7,3, 2H), 2,29 (t,J=7,3, 2H), 1,86-to 1.77 (m, 2H), 1,25 (t,J=7,1, 3H).

Example 399

Ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using cyclopropanemethylamine, and in example 379, step A, using the ethyl ester of 4-pamakani acid. Mass spectrum (ESI): mass calculated for C25H30N2About3S, 438,20; m/z found 439,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,35 (t,J=8,1, 1H), 7,27-7,20 (m, 5H), 6,67 (Sirs, 1H), 4,10 (DD,J=7,1, 7,1, 2H), 2,83-a 2.71 (m, 4H), 2,60 (t,i> J=7,1, 2H), 2.40 a (t,J=6,6, 2H), 2,31 (t,J=7,3, 2H), 1,81-1,72 (m, 2H), 1,23 (t,J=7,1, 3H), 0.88 to 0,79 (m, 1H), 0,52-of 0.45 (m, 2H), 0,13-0,07 (m, 2H).

Example 400

2-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using cyclopropanemethylamine, and in example 379, step A, using 2-(3-bromopropyl)isoindole-1,3-dione. Mass spectrum (ESI): mass calculated for C30H29N3About3S, 511,19; m/z found 512,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,84-to 7.77 (m, 2H), 7,72-7,63 (m, 3H), 7,60 (l,J=7,8, 1H), 7,34 (t,J=8,1, 1H), 7,27-to 7.18 (m, 5H), 3,71 (t,J=7,1, 2H), 2,82-2,70 (m, 4H), 2,65 (t,J=7,6, 2H), 2,39 (l,J=6,6, 2H), 1,88-to 1.79 (m, 2H), 0,87-0,76 (m, 1H), 0,50 at 0.42 (m, 2H), 0.12 to 0.06 to (m, 2H).

Example 401

4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid

Specified in the title compound was obtained from the compound of example 399, in accordance with the procedure described in example 379, step C. Mass spectrum (ESI): mass calculated for C23H26N2About3S, 410,17; m/z found 411,4 [M+H]+.1H NMR (400 MHz, CD3OD): 7,42 (l,J=7,8, 1H), 7,31 (l,J=7,8, 1H), 7,16-7,10 (m, 2H), 7,07 (t,J=7,8, 1H),? 7.04 baby mortality-7,00 (m, 2H), of 6.96 (t,J=7,8, 1H), 3,23-3,11 (m, 2H), of 3.07 (t,J=7,8, 2H), 2,1-2,77 (m, 4H), 2,19 (t,J=7,1, 2H), 1,78 by 1.68 (m, 2H), 0,91-of 0.82 (m, 1H), 0,49-0,41 (m, 2H), of 0.20 to 0.13 (m, 2H).

Example 402

1-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using 1-(3-aminopropyl)pyrrolidin-2-it. Mass spectrum (ESI): mass calculated for C22H25N3About2S, 395,17; m/z found 396,4 [M+H]+.1H NMR (400 MHz, CD3OD): to 7.67 (d,J=8,1, 1H), 7,60 (l,J=8,1, 1H), 7,32 (t,J=7,8, 1H), 7,28-to 7.15 (m, 5H), 5,61 (Sirs, 1H), 3,34-of 3.25 (m, 4H), 2,94-of 2.81 (m, 4H), 2,65 (t,J=7,3, 2H), 2,32 (t,J=7,8, 2H), 1,94 (t,J=7,3, 2H), 1,79 was 1.69 (m, 2H).

Example 403

N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylmethyl-1,3-diamine

To a solution of 2-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione (example 400, 3.0 g, 5,86 mmol) in EtO (12 ml) was added hydrazine (220 μl, 7.03 mmol). The reaction mixture was stirred at room temperature for 24 h the Mixture was dissolved in CH2Cl2(200 ml), washed with saturated Panso3(2×20 ml) and H2O (1×20 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS (330 g; 0-10% 2M NH3in CH3HE/CH2Cl2) and received a clear oil (2,13 g, yield 96%). Mass spectrum (ESI): mass calculated for C22H27N3OS; 381,2; m/z found 382,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.68 (d,J=8,1, 1H), 7,58 (l,J=8,1, 1H), 7,31 (t,J=8,1, 1H), 7.24 to 7,16 (m, 5H), 2,79-a 2.71 (m, 4H), to 2.67 (t,J=6,8, 2H), 2,59 (t,J=6,8, 2H), 2,37 (l,J=6,6, 2H), 2,07 (s, 2H), 1,62-of 1.52 (m, 2H), 0,87 of 0.77 (m, 1H), and 0.50 to 0.44 (m, 2H), 0.12 to 0.06 to (m, 2H).

Example 404

Methyl ester 5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentanol acid

Specified in the title compound was obtained in accordance with the procedure described in example 379, step A, using methyl ester 5-bromopentanoate acid. Mass spectrum (ESI): mass calculated for C24H28N2About3S, 424,18; m/z found 425,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), was 7.36 (t,J=8,1, 1H), 7,27-7,20 (m, 5H), the 3.65 (s, 3H), 2,85 is 2.80 (m, 4H), 2,66 (t,J=7,6, 2H), 2,33 (t,J=7,6, 2H), 1,81 is 1.75 (m, 1H), 1,67 of 1.50 (m, 4H), 0,52-0,40 (m, 2H), 0,43 is 0.37 (m, 2H).

Example 405

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide

To a solution of N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1 - cyclopropylmethyl-1,3-diamine (example 403, 180 mg, 0.47 mmol) in CH2Cl2(10 ml) was added to ritilin (131 μl, to 0.94 mmol) and then acetic anhydride (76 μl, 0.71 mmol). The reaction mixture was stirred at room temperature for 24 h the Mixture was dissolved in CH2Cl2(100 ml), washed with saturated Panso3(2×15 ml) and H2O (1×15 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(12 g, 0-10% CH3HE/CH2Cl2) and received solid white (154 mg, yield 77%). Mass spectrum (ESI): mass calculated for C24H29N3OS; 423,2; m/z found 424,4 [M+H]+.1H NMR (400 MHz, CDCl3): RS 9.69 (Sirs, 1H), to 7.67 (d,J=8,1, 1H), 7.62mm (l,J=8,1, 1H), 7,33 (t,J=8,1, 1H), 7,27-7,17 (m, 5H), of 3.27 (DD,J=6,6, 5,6, 2H), 2,96-2,89 (m, 2H), 2,87-of 2.81 (m, 2H), 2,78 (t,J=6,8, 2H), 2,53 (l,J=6,8, 2H), of 1.88 (s, 3H), 1,76-to 1.67 (m, 2H), 0,94-0,83 (m, 1H), 0.60 and of 0.53 (m, 2H), by 0.21 to 0.15 (m, 2H).

Example 406

[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide morpholine-4-carboxylic acid

Specified in the title compound was obtained in accordance with the procedure described in example 405, using morpholine-4-carbonylchloride. Mass spectrum (ESI): mass calculated for C28H34N4About3S, 494,24; m/z found 495,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.69 (t,J=8,5, 2H),7,41-of 7.23 (m, 6H), 6,85 (Sirs, 1H), 3,68-of 3.60 (m, 4H), 3,51 is 3.40 (m, 6H), 3,39-of 3.27 (m, 4H), 3,26-3,17 (m, 2H), 3,09-a 3.01 (m, 2H), 2,19-to 2.06 (m, 2H), 1,25-to 1.14 (m, 1H), 0,85-0,76 (m, 2H), 0,53-of 0.45 (m, 2H).

Example 407

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methansulfonate

Specified in the title compound was obtained in accordance with the procedure described in example 405, using methanesulfonanilide. Mass spectrum (ESI): mass calculated for C23H29N3About3S2, 459,17; m/z found 460,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.67 (t,J=8,6, 2H), 7,39-7,17 (m, 6H), 7,06 (Sirs, 1H), 3.43 points-to 3.09 (m, 8H), 3,07 are 2.98 (m, 2H), 2,96 (s, 3H), 2,20-2,07 (m, 2H), 1,23-1,11 (m, 1H), 0.79, which is 0.67 (m, 2H), 0,49-0,41 (m, 2H).

Example 408

5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentane acid

Specified in the title compound was obtained from compound example 379 in accordance with the procedure described in example 404, step C. Mass spectrum (ESI): mass calculated for C23H26N2About3S, 410,17; m/z found 411,3 [M+H]+.1H NMR (400 MHz, CDCl3): KZT 12.39 (Sirs, 1H), 7,71 (l,J=7,8, 1H), 7.62mm (d, J=7,8, 1H), 7,35 (t,J=7,8, 1H), 7,31-7,20 (m, 5H), 3.04 from-2,90 (m, 4H), 2,82 (t,J=7,8, 2H), 2,30 (t,J=6,8, 2H), 1,98 is 1.91 (m, 1H), 1,72-and 1.54 (m, 4H), 0,83-0,76 (m, 2H), 0,63 is 0.55 (m, 2H).

Example 409

1-[3-({2-[4-(benzothiazol-yloxy)phenyl]ethyl}isopropylamino)propyl]pyrrolidin-2-he

A mixture of 1-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-it (example 402, 500 mg, of 1.26 mmol) and acetone (185 μl, 2,52 mmol) in CH2Cl2(25 ml) was stirred at room temperature for 1 hour. To the mixture was added N(SLA)3(536 mg, 2,52 mmol). The mixture was stirred at room temperature for 16 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(100 ml) and concentrated under reduced pressure to obtain the crude product as a yellow oil. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2). The desired fractions were combined and concentrated under reduced pressure to obtain a clear oil, which crystallized upon standing (290 mg, yield 53%). Mass spectrum (ESI): mass calculated for C25H31N3About2S; 437,21; m/z found 438,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,3, 1H), 7,66 (l,J=8,3, 1H), 7,38 (t,J=8,3, 1H), 7,28-of 7.23 (m, 5H), 3,35 (t,J=6,8, 2H), 3.27 to (t,J=7,3, 2H), 3,05-2,95 (m, 1H), 2,78-2,70 (m, 2H), 2,69-2,61 (m, 2H), 2,47 (t,J=7,3, 2H), 2,37 (t,J=8,1, 2H), 2,04-of 1.94 (m, 2H), 1,69 is 1.58 (m, 2H), 0,99 (l,J=6,8, 6H).

Example 410

1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the methodology described is Oh in example 409, using cyclopropanecarboxaldehyde. Mass spectrum (ESI): mass calculated for C26H31N3About3S, 449,21; m/z found 450,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=7,8, 1H), to 7.64 (d,J=8,1, 1H), was 7.36 (t,J=7,8, 1H), 7,32-7,21 (m, 5H), 3,38 (t,J=7,1, 2H), and 3.31 (t,J=7,1, 2H), 3,09-to 3.02 (m, 2H), 2.95 and-and 2.83 (m, 4H), 2,72 (l,J=7,1, 2H), 2,37 (t,J=7,8, 2H), 2.05 is-of 1.95 (m, 2H), 1,92-to 1.82 (m, 2H), 1,02-of 0.91 (m, 1H), 0,66 is 0.59 (m, 2H), of 0.29 to 0.23 (m, 2H).

Example 411

1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he

To a solution of 1-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-it (example 402, 500 mg, of 1.26 mmol) in EtO (20 ml) was added acetic acid (716 μl, of 1.26 mmol), molecular sieves (500 mg, 3E), (1 amoxilcompare)trimethylsilane (1,51 ml, 7,58 mmol) and cyanoborohydride sodium (357 mg, 5,69 mmol). The reaction mixture is boiled under reflux for 16 h, cooled, filtered through a layer of diatomaceous earth, and then washed CH2Cl2(100 ml) and concentrated under reduced pressure to obtain the crude product as a clear oil. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2). The desired fractions were combined and concentrated under reduced pressure to obtain solid white (434 mg, yield 66%). Mass spectrum (ESI): mass, in the numerical C 25H29N3About2S; 435,2; m/z found 436,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=7,8, 1H), to 7.64 (d,J=7,8, 1H), was 7.36 (t,J=7,8, 1H), 7,28-7,19 (m, 5H), to 3.36 (t,J=7,1, 2H), 3,28 (t,J=7,1, 2H), 2,87 is 2.80 (m, 4H), to 2.67 (t,J=7,3, 2H), 2,37 (t,J=7,8, 2H), 2,03-of 1.94 (m, 2H), 1,82 is 1.70 (m, 3H), 0,53 of 0.47 (m, 2H), 0,43 is 0.38 (m, 2H).

Example 412

1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}propylamino)propyl]pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 409, using Propionaldehyde. Mass spectrum (ESI): mass calculated for C25H31N3About2S, 437,21; m/z found 438,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,38 (t,J=8,1, 1H), 7,29-of 7.24 (m, 5H), 3,39 (t,J=7,1, 2H), 3,30 (t,J=7,1, 2H), 2,86 is 2.80 (m, 4H), 2,64 (t,J=7,6, 2H), 2,58 (t,J=7,6, 2H), 2,42 to 2.35 (m, 2H), 2,07-of 1.97 (m, 2H), 1,80-1,71 (m, 2H), 1,59 to 1.47 (m, 2H), 0,92 (l,J=7,3, 3H).

Example 413

Ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid

Specified in the title compound was obtained in accordance with the procedure described in example 409, using 1-acetylpiperidine-4-it. Mass spectrum (ESI): mass calculated for C28H35N3About4S, 509,23; m/z found 510,4 [M+H]+.1H NMR (400 MHz, CDC 3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,38 (t,J=8,1, 1H), 7,29-of 7.23 (m, 5H), 4,69 (l,J=13,1, 1H), 4,13 (DD,J=7,8, 6,8, 2H), 3,85 (l,J=13,4, 1H), 3,09 are 2.98 (m, 2H), 2,79-to 2.74 (m, 4H), 2,60 (t,J=6,8, 2H), 2,52 is 2.44 (m, 3H), 2,04 (s, 3H), 1.85 to at 1.73 (m, 4H), 1,48-of 1.35 (m, 2H), 1.26 in (t,J=7,1, 3H).

Example 414

Ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid

Specified in the title compound was obtained in accordance with the procedure described in example 409, using 1-methylpiperidin-4-it. Mass spectrum (ESI): mass calculated for C27H35N3About3S, 481,2; m/z found 482,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,37 (t,J=8,1, 1H), 7,28-7,19 (m, 5H), of 4.12 (DD,J=7,3, 7,1, 2H), 3,11 (l,J=12,1, 2H), 2,75-2,69 (m, 4H), 2,58-of 2.50 (m, 3H), of 2.38 (s, 3H), 2,29 (t,J=7,1, 2H), 2,24-of 2.15 (m, 2H), 2,03-of 1.97 (m, 2H), 1,73 (t,J=6,3, 4H), 1,25 (t,J=7,1, 3H).

Example 415

4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methanesulfonamide)butyric acid

Specified in the title compound was obtained from compound example 398 in accordance with the procedure described in example 407 in example 379, step C. Mass spectrum (ESI): mass calculated for C20H22N2About5S2, of 434.1; m/z found 435,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H) 7,38 (t, J=8,1, 1H), 7,33-of 7.24 (m, 5H), 3,48 (t,J=7,6, 2H), 3,20 (t,J=7,6, 2H), 2,96 (t,J=7,3, 2H), 2,77 (s, 3H), 2,37 (t,J=6,6, 2H), 1.91 a-is 1.81 (m, 2H).

Example 416

({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 379, stages a and b, using methyl ester bromoxynil acid. Mass spectrum (ESI): mass calculated for C20H20N2About3S, 368,12; m/z found 369,3 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), 7,37 (t,J=8,1, 1H), 7,31-7,22 (m, 5H), to 3.64 (s, 2H), 3,26 (DD,J=7,6, 3,3, 2H), 2,98 (DD,J=7,6, 3,3, 2H), 2,50 is 2.43 (m, 1H), 0,84-of 0.79 (m, 2H), 0,71 is 0.65 (m, 2H).

Example 417

Ethyl ester of 6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid

Specified in the title compound was obtained in accordance with the procedure described in example 379, step A, using the ethyl ester of 6-Bromhexine acid. Mass spectrum (ESI): mass calculated for C26H32N2About3S, 452,21; m/z found 453,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), was 7.36 (t,J=8,1, 1H), 7,28-7,20 (m, 5H), of 4.12 (DD,J=7,3, 7,1, 2H), 2,87-of 2.81 (m, 4H), 2,65 (t,J=7,8, 2H), 2,30 (t,J=7,6, 2H), 1,81-of 1.74 (m, 1H), 1,69 is 1.60 (m, 2H), 1,59 of 1.50 (m, 2H), 1,37-1.27mm (who, 2H), 1,24 (t,J=7,1, 3H), 0,52-0,46 (m, 2H), 0,43 is 0.37 (m, 2H).

Example 418

Ethyl ester of 7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid

Specified in the title compound was obtained in accordance with the procedure described in example 379, step A, using the ethyl ester of 7-bromoheptanoate acid. Mass spectrum (ESI): mass calculated for C27H34N2About3S, 466,23; m/z found 467,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), 7,60 (l,J=8,1, 1H), 7,34 (t,J=8,1, 1H), 7,27-to 7.18 (m, 5H), 4,10 (DD,J=7,1, 7,1, 2H), 2,86-and 2.79 (m, 4H), 2.63 in (t,J=7,6, 2H), 2,28 (t,J=7,6, 2H), 1,80-of 1.74 (m, 1H), 1,67 is 1.58 (m, 2H), 1.57 in to 1.47 (m, 2H), 1,38-1,25 (m, 4H), of 1.23 (t,J=7,1, 3H), of 0.50 to 0.44 (m, 2H), 0,43 is 0.37 (m, 2H).

Example 419

6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid

Specified in the title compound was obtained from the compound of example 417 in accordance with the procedure described in example 379 stage C. Mass spectrum (ESI): mass calculated for C24H26N2About3S, 424,18; m/z found 425,4 [M+H]+.1H NMR (400 MHz, CDCl3): 11,17 (Sirs, 1H), 7,69 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,39-7,21 (m, 6H), 3,35 of 3.28 (m, 2H), 3,24-3,10 (m, 4H), 2,53 at 2.45 (m, 1H), 2,31 (t,J=7,1, 2H), 1,92-of 1.81 (m, 2H), 1.70 to to 1.61 (m, 2H), 1,44 is 1.34 (m, 4H), 0,91-0,83 (m, 2H).

Example 420

7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid

Specified in the title compound was obtained from the compound of example 418 in accordance with the procedure described in example 379 stage C. Mass spectrum (ESI): mass calculated for C25H30N2About3S, 438,2; m/z found 439,4 [M+H]+.1H NMR (400 MHz, CDCl3): 12,57 (Sirs, 1H), 7,72 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), was 7.36 (t,J=8,1, 1H), 7,31-7,20 (m, 5H), 3,02-2,90 (m, 4H), 2,78 (t,J=7,8, 2H), 2.26 and (t,J=7,6, 2H), 1,97-1,90 (m, 1H), 1,67-of 1.56 (m, 4H), 1.41 to of 1.26 (m, 4H), 0,80-to 0.73 (m, 2H), 0,62 is 0.55 (m, 2H).

Example 421

N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine

Specified in the title compound was obtained in accordance with the procedure described in example 378, step A, using cyclopropylamine in example 379, step A, using 2-(3-bromopropyl)isoindole-1,3-dione, and in example 403. Mass spectrum (ESI): mass calculated for C21H25N3OS, 367,17; m/z found 468,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=7,6, 1H), 7,65 (l,J=7,8, 1H), 7,38 (t,J=7,6, 1H), 7,29-of 7.23 (m, 5H), 2,89-2,82 (m, 4H), 2,71 (t,J=7,1, 4H)and 1.83-1.77 in (m, 1H), 1,72-of 1.64 (m, 2H), 1.55V (Sirs, 2H), 0,54-of 0.48 (m, 2H), of 0.44 to 0.39 (m, 2H).

Example 422

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide

Pointed to by the e in the title compound was obtained from the compound of example 421 in accordance with the methodology described in example 405. Mass spectrum (ESI): mass calculated for C23H27N3About2S, 409,18; m/z found 410,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), was 7.36 (t, J=8,0118, 1H), 7,28-7,21 (m, 5H), 6,77 (Sirs, 1H), 3,26 (DD,J=6,1, 5,8, 2H), 2,89-and 2.83 (m, 4H), 2,75 (t,J=6,8, 2H), 1,89 (s, 3H), 1,84-of 1.78 (m, 1H), 1,75-to 1.67 (m, 2H), 0,57-of 0.51 (m, 2H), 0,47 at 0.42 (m, 2H).

Example 423

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isobutyramide

Specified in the title compound was obtained in accordance with the procedure described in example 421, using isobutyramide. Mass spectrum (ESI): mass calculated for C25H31N3About2S, 437,21; m/z found 438,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,37 (t,J=8,1, 1H), 7,30-of 7.23 (m, 5H), 6,54 (Sirs, 1H), 3,30 (DD,J=6,1, 5,8, 2H), 2,90-and 2.83 (m, 4H), 2,77 (t,J=6,3, 2H), 2,31-2,19 (m, 1H), 1.85 to of 1.78 (m, 1H), 1,75-to 1.67 (m, 2H), 1,12 (l,J=6,8, 6H), 0,58-0,52 (m, 2H), 0,45-0,40 (m, 2H).

Example 424

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]benzamide

Specified in the title compound was obtained in accordance with the procedure described in example 422, using benzoyl chloride. Mass spectrum (ESI): mass calculated for C28H29N3About2S, 471,20; m/z found 472,4 [M+H]+ 1H NMR (400 MHz, CDCl3): 7,78-to 7.67 (m, 4H), to 7.61 (d,J=7,8, 1H), 7,44-7,39 (m, 1H), 7,38-7,31 (m, 3H), 7,25-7,13 (m, 5H), 3,50 (DD,J=6,1, 5,6, 2H), 2,89-2,77 (m, 6H), 1.85 to about 1.75 (m, 3H), 0.56 to 0,49 (m, 2H), 0,45-0,38 (m, 2H).

Example 425

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-4-chlorobenzamide

Specified in the title compound was obtained in accordance with the procedure described in example 422, using 4-chlorobenzylchloride. Mass spectrum (ESI): mass calculated for C28H28ClN3About2S, 505,16; m/z found 506,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,80 (t,J=5.0, 1H), 7.68 per (e,J=7,6, 1H), 7,65-to 7.59 (m, 3H), 7,37-7,29 (m, 3H), 7,25-to 7.15 (m, 5H), 3,47 (DD,J=6,1, 5,31, 2H), 2,89-2,77 (m, 6H), of 1.84 and 1.75 (m, 3H), 0,57-of 0.51 (m, 2H), 0,42-0,36 (m, 2H).

Example 426

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide

Specified in the title compound was obtained in accordance with the procedure described in example 422, using methanesulfonanilide. Mass spectrum (ESI): mass calculated for C22H27N3About3S2, 445,15; m/z found 446,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=7,8, 1H), to 7.64 (d,J=7,8, 1H), was 7.36 (t,J=7,8, 1H), 7,28-7,21 (m, 5H), 6,03 (Sirs, 1H), 3.15 in (t,J=6,1, 2H), 2,88 (s, 3H), 2,87-2,82 (m, 4H), 2,78 (t,J=6,1, 2H), 1,82-1,71 (m, 3H), 0,58-0,52 (m, 2H), 0,49-0,43 (m, 2H).

Example 427

Triftoratsetata salt [3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide propane-2-sulfonic acid

Specified in the title compound was obtained in accordance with the procedure described in example 422, using propane-2-sulphonylchloride. Mass spectrum (ESI): mass calculated for C24H31N3About3S2, 473,18; m/z found 474,4 [M+H]+.1H NMR (400 MHz, CD3OD): the 7.65 (d,J=7,8, 1H), 7,53 (l,J=8,1, 1H), 7,39-7,16 (m, 6H), 3,44 (t,J=8,3, 2H), 3,37 (t,J=8,3, 2H), 3,24-3,19 (m, 2H), 3,16-of 3.06 (m, 4H), 2,87-2,78 (m, 1H), 2,07-of 1.94 (m, 2H), 1,67 (l,J=4,04, 3H), 1,23 (l,J=6,1, 3H), of 1.07 to 1.00 (m, 2H), 0,98-of 0.91 (m, 2H).

Example 428

Ethyl ester 8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid

Specified in the title compound was obtained in accordance with the procedure described in example 379, step A, using the ethyl ester of 8-bromooctanoate acid. Mass spectrum (ESI): mass calculated for C28H36N2About3S, 480,43; m/z found 481,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), was 7.36 (t,J=8,1, 1H), 7,27-7,20 (m, 5H), 4,11 (DD,J=7,3, 7,1, 2H), 2,87-of 2.81 (m, 4H), 2,64 (t,J=7,3, 2H), 2,28 (t,J=7,1, 2H), 1,82 is 1.75 (m, 1H), 1,66 is 1.58 (m, 2H), 1.56 to about 1.47 (m, 2H), 1,36-of 1.27 (m, 6H), 1,24 (t,J=7,1, 3H), 0,51-of 0.45 (m, 2H), 0,43 is 0.38 (m, 2H).

Note the p 429

1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-3-prilocaine

Specified in the title compound was obtained in accordance with the procedure described in example 422, using phenylisocyanate. Mass spectrum (ESI): mass calculated for C28H30N4About2S, 486,21; m/z found 487,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.61 (d,J=8,1, 1H), EUR 7.57 (d,J=8,1, 1H), 7,28 (t,J=8,1, 1H), 7,20-to 7.09 (m, 10H), 6.89 in (t,J=7,3, 1H), 5,64 (Sirs, 1H), 3,16-to 3.09 (m, 2H), 2,70-of 2.64 (m, 4H), 2.57 m (t,J=7,1, 2H), 1,67-to 1.60 (m, 1H), 1.60-to of 1.52 (m, 2H), 0,39 is 0.33 (m, 2H), from 0.25 to 0.20 (m, 2H).

Example 430

8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid

Specified in the title compound was obtained from the compound of example 428 in accordance with the procedure described in example 379, step C. Mass spectrum (ESI): mass calculated for C26H32N2About3S, 452,21; m/z found 453,4 [M+H]+.1H NMR (400 MHz, CDCl3): 12,76 (Sirs, 1H), 7,72 (l,J=7,6, 1H), 7,63 (l,J=7,8, 1H), was 7.36 (t,J=7,6, 1H), 7,30-7,21 (m, 5H), 3,01-is 2.88 (m, 4H), 2,77 (t,J=8,1, 2H), and 2.27 (t,J=7,8, 2H), 1,96-of 1.88 (m, 1H), 1,66-and 1.54 (m, 4H), 1,38 is 1.23 (m, 6H), 0.77-a is 0.70 (m, 2H), and 0.61-of 0.54 (m, 2H).

Example 431

[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide tetrahydrofuran-2-carboxylic acid is you

To a solution of N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine (example 421, 330 mg, 0.9 mmol) in CH2Cl2(18 ml) was added 2-tetrahydrofuroyl acid (129 μl, 1.35 mmol) and Si-carbodiimide (1.05 mmol/g, 1,71 g, 1.8 mmol). The reaction mixture was stirred at room temperature over night, filtered and concentrated. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2) and received solid white (267 mg, yield 64%). Mass spectrum (ESI): mass calculated for C26H31N3About3S; 465,21; m/z found 466,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), was 7.36 (t,J=8,1, 1H), 7,32 (Sirs, 1H), 7,29-7,21 (m, 5H), 4,32 (DD,J=6,1, 2,3, 1H), 3,93-3,81 (m, 2H), 3,41-of 3.31 (m, 1H), 3,30-is 3.21 (m, 1H), 2,90 is 2.80 (m, 4H), 2,75 (t,J=6,8, 2H), 2,32-of 2.21 (m, 1H), 2,08-of 1.97 (m, 1H), 1,92-to 1.77 (m, 3H), 1,76-to 1.67 (m, 2H), 0.56 to 0,49 (m, 2H), 0,48-0,41 (m, 2H).

Example 432

N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-2-hydroxyacetamido

Specified in the title compound was obtained in accordance with the procedure described in example 431, using glycolic acid. Mass spectrum (ESI): mass calculated for C23H27N3About3S, 425,18; m/z found 426,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73-7,63 (m, 2H), 7,44 (Sirs, 1H), 7,40-7,33 (m, 1H), 7,29-to 7.18 (m, 5H), is 4.21 (s, 1H), 3,91(s, 2H), 3,37 of 3.28 (m, 2H), 2,90-2,82 (m, 4H), 2,75 (t,J=6,1, 2H), 1.85 to of 1.78 (m, 1H), 1,77 is 1.70 (m, 2H), 0,58-0,38 (m, 4H).

Example 433

4-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)butyric acid

A. {2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamine.

To a stirred solution of 2-[4-(2-bromoethoxy)phenoxy]benzothiazole (example 9; 1.1 g, 3.14 mmol) in CH3JV (31 ml) was added cyclopropylamine (1,09 ml, 15.7 mmol) and N,N-diisopropylethylamine (1.1 ml, 6,28 mmol). The mixture was heated to 60°C for 16 h, then cooled to room temperature and was dissolved in CH2Cl2(100 ml). The solution was washed H2O (2×20 ml), dried and concentrated. The resulting oil was purified on SIO, SIS2(40 g; 0-15% CH3HE/CH2Cl2) and received a clear oil (999 mg, yield 98%). Mass spectrum (ESI): mass calculated for C18H18N2About2S; 326,11; m/z found 327,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.59 (d, J=8,1, 1H), 7,33 (t,J=8,1, 1H), 7,27-7,17 (m, 3H), 6,95-6,89 (m, 2H), 4,03 (t,J=5,3, 2H), 3,06 (t,J=5,3, 2H), 2,20-and 2.14 (m, 1H), 2,02 (Sirs, 1H), 0,47-0,41 (m, 2H), 0.39 to-0,34 (m, 2H).

C. Ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)butyric acid.

To a stirred solution of {2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamine (950 mg, only 2.91 mmol) in CH3JV (29 ml) was added ethyl ester 4-b is mmaslano acid (625 μl, 4,37 mmol) and N,N-diisopropylethylamine (1.0 ml, of 5.82 mmol). The mixture was heated to 60°C for 16 h, cooled to room temperature and was dissolved in CH2Cl2(100 ml). The solution was washed H2O (2×20 ml), dried and concentrated. The resulting oil was purified on SIO, SIS2(40 g; 0-50% EtOAc/hexane) to give colorless oil (1.0 g, yield 78%). Mass spectrum (ESI): mass calculated for C24H28N2O4S; 440,18; m/z found 441,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.61 (d,J=8,1, 1H), 7,34 (t,J=8,1, 1H), 7,28-to 7.18 (m, 3H), 6,95-of 6.90 (m, 2H), 4,14-Android 4.04 (m, 4H), 3.00 and (t,J=6,3, 2H), 2,71 (t,J=7,1, 2H), 2,31 (t,J=7,1, 2H), 1,90 and 1.80 (m, 3H), of 1.23 (t,J=7,1, 3H), 0,51 to 0.44 (m, 2H), 0,43 is 0.38 (m, 2H).

C. 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid.

To a solution of ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)butyric acid (970 mg, 2.2 mmol) in a mixture of THF/CH3HE, 3:1, (80 ml) was added lithium hydroxide (211 mg, 8,8 mmol) in water (20 ml). The solution was stirred at room temperature for 16 hours and then the pH was brought to 7 by adding 1N. aqueous HCl. The mixture was extracted with CH2Cl2(2×100 ml). The combined organic phase was concentrated under reduced pressure. The resulting oil was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2) and received solid white (877 mg, yield 97%). Mac the spectrum (ESI): mass, calculated for C22H24N2About4S; 412,15; m/z found 413,3 [M+H]+.1H NMR (400 MHz, CDCl3): 11,44 (Sirs, 1H), 7.68 per (e,J=8,1, 1H), 7.62mm (l,J=8,1, 1H), 7,35 (t,J=8,1, 1H), 7,27-7,20 (m, 3H), 7,01-to 6.95 (m, 2H), of 4.44 (t,J=5,0, 2H), 3,56 (t,J=5,005, 2H), 3,32 (t,J=8,1, 2H), 2,67-2,60 (m, 1H), 2,46 (t,J=6,8, 2H), 2,18-of 2.09 (m, 2H), 1.32 to 1,25 (m, 2H), 0.88 to 0,81 (m, 2H).

Example 434

1-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 251, step B, using 1-(3-aminopropyl)pyrrolidin-2-it. Mass spectrum (ESI): mass calculated for C21H23N3About2S, 381,15; m/z found 382,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), 7,45-7,41 (m, 2H), was 7.36 (t,J=8,1, 1H), 7,32-7,28 (m, 2H), 7,24 (t,J=8,1, 1H), 3,81 (s, 2H), 3,38-of 3.27 (m, 5H), 3,63 (t,J=6,8, 2H), 3,35 (t,J=7,6, 2H), 2,02-of 1.93 (m, 2H), 1,82-of 1.73 (m, 2H).

Example 435

1-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 409, using formaldehyde. Mass spectrum (ESI): mass calculated for C22H25N3About2S, 395,17; m/z found 396,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.64 (is, J=8,1, 1H), 7,43-7,27 (m, 5H), 7,24 (t,J=8,1, 1H), 3,54 (s, 2H), 3,32 (DD,J=7,1, 7,1, 4H), 2,43 (t,J=7,1, 2H), 2,34 (t,J=7,1, 2H), of 2.23 (s, 3H), 2.00 in at 1.91 (m, 2H), 1,80 is 1.70 (m, 2H).

Example 436

1-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 409, using acetone. Mass spectrum (ESI): mass calculated for C24H29N3About2S, 423,20; m/z found 424,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,45-7,40 (m, 2H), 7,37 (t,J=7,8, 1H), 7,30-7,21 (m, 3H), 3,55 (s, 2H), 3,29-3,20 (m, 4H), 3,01-2,90 (m, 1H), 2,42 (t,J=7,1, 2H), 2,32 (t,J=7,8, 2H), 1,97 of-1.83 (m, 2H), 1,63-of 1.53 (m, 2H), 1,02 (l,J=6,6, 6H).

Example 437

1-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-he

Specified in the title compound was obtained in accordance with the procedure described in example 409, using acetaldehyde. Mass spectrum (ESI): mass calculated for C23H27N3About2S, 409,18; m/z found 410,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,43-7,34 (m, 3H), 7,32-of 7.23 (m, 3H), of 3.56 (s, 2H), 3,30 (DD,J=7,1, 7,1, 4H), 2,53 (DD,J=7,1, 7,1, 2H), 2,45 (t,J=7,1, 2H), 2,34 (t,J=7,8, 2H), 2.00 in at 1.91 (m, 2H), 1,73-of 1.64 (m, 2H), 1,04 (t,J=7,1, 3H).

Example 438

[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine

Specified in the title compound was obtained in accordance with the procedure described in example 251, step B, using cyclopropylamine. Mass spectrum (ESI): mass calculated for C17H16N2OS, 296,10; m/z found 297,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,40-7,33 (m, 3H), 7,32-7,27 (m, 2H), 7,24 (t,J=8,1, 1H), 3,85 (s, 2H), 2,19-2,12 (m, 1H), 1,86 (Sirs, 1H), 0,48-0,35 (m, 4H).

Example 439

N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine

Specified in the title compound was obtained in accordance with the procedure described in example 421, using the compound of example 438. Mass spectrum (ESI): mass calculated for C20H23N3OS, 353,16; m/z found 354,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,41-to 7.32 (m, 3H), 7,30-of 7.23 (m, 3H), of 3.75 (s, 2H), to 2.67 (t,J=7,1, 2H), 2,58 (t,J=7,1, 2H), 1,80-of 1.73 (m, 1H), 1,72-of 1.64 (m, 2H), 1,19 (Sirs, 2H), 0,52-0,46 (m, 2H), 0,42-0,36 (m, 2H).

Example 440

N-[3-({4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)isobutyramide

Specified in the title compound was obtained in accordance with the procedure described in example 422, using isobutyramide. Mass spectrum (ESI): mass calculated for C24H 29N3About2S, 423,20; m/z found 424,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,40-7,22 (m, 6H), 6,26 (Sirs, 1H), of 3.73 (s, 2H), 3,23 (DD,J=6,3, 5,8, 2H), 2,61 (t,J=6,6, 2H), 2,29-to 2.18 (m, 1H), 1,79 by 1.68 (m, 3H), 1,09 (l,J=6,8, 6H), 0,54 of 0.47 (m, 2H), 0,43 is 0.37 (m, 2H).

Example 441

1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-2-isopropylamino

Specified in the title compound was obtained in accordance with the procedure described in example 422, using isopropylmalate. Mass spectrum (ESI): mass calculated for C24H30N4About2S, 438,21; m/z found 439,4 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.69 (d,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,38-7,29 (m, 3H), 7,27-7,20 (m, 3H), 5,44 (Sirs, 1H), 5,15 (l,J=7,8, 1H), a 3.87 is 3.76 (m, 1H), 3,70 (s, 2H), 3,12 (DD,J=6,3, 6,1, 2H), 2,56 (t,J=7,1, 2H), 1,76-to 1.67 (m, 3H), of 1.07 (d,J=6,3, 6H), 0,49 at 0.42 (m, 2H), 0,40-0,34 (m, 2H).

Example 442

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-isopropylamino

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using isopropylmalate. Mass spectrum (ESI): mass calculated for C23H28N4About2S, 424,19; m/z found 425,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), to 7.67 (d,J=8,1, 1H), 7,41-7,35 (m,3H), 7,32-7,24 (m, 3H), of 4.77 (DD,J=8,1, 7,8, 1H), 3,88-of 3.78 (m, 1H), 3,66-3,55 (m, 1H), 3,51 (s, 2H), 2,82 (l,J=11,6, 2H), 2.13 in (t,J=10,9, 2H), 1,94 (l,J=11,9, 2H), 1.69 in (Sirs, 1H), 1,48-of 1.36 (m, 2H), 1.14 in (q,J=6,6, 6H).

Example 443

Methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using methyl ester Chlorococcales acid. Mass spectrum (ESI): mass calculated for C22H23N3About4S, 425,14; m/z found to 426.2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,78 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), 7,55 is 7.50 (m, 2H), 7,44 and 7.36 (m, 3H), 7,31 (t,J=8,1, 1H), 3,84 (s, 2H), 3,81-and 3.72 (m, 1H), 3,41 (s, 3H), 3,11 (l,J=10,9, 2H), 2,59-2,47 (m, 2H), 2.00 in at 1.91 (m, 2H), 1,79-of 1.66 (m, 2H).

Example 444

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide

Specified in the title compound was obtained in accordance with the procedure described in example 253, using isobutyramide. Mass spectrum (ESI): mass calculated for C23H27N3About2S, 409,18; m/z found 410,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.84 (d,J=8,6, 2H), 7,69 (t,J=7,8, 2H), 7,44 (l,J=8,6, 2H), 7,41-7,33 (m, 2H), 7,27 (t,J=8,1, 1H), 4,33 (s, 2H), 4,16-4,00 (m, 1H), 3,57-of 3.42 (m, 2H), 3,31-and 3.16 (m, 2H), 2,58 at 2.45 (m, 1H), 2,31-2,07 (m, 4H), 1,10 (l,J=6,8, 6H).

p> Example 445

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid

Specified in the title compound was obtained from the compound of example 253, step D, in accordance with the procedure described in example 431. Mass spectrum (ESI): mass calculated for C24H27N3About3S, 437,18; m/z found 438,3 [M+H]+.1H NMR (400 MHz, CDCl3): 11,03 (Sirs, 1H), 7,73 (l,J=7,8, 1H), to 7.67 (d,J=7,8, 1H), 7,46-7,42 (m, 2H), 7,41-to 7.32 (m, 3H), 7,27 (l,J=7,8, 1H), or 4.31 (t,J=8.34 per, 1H), 3,98-to 3.89 (m, 1H), 3,84 (s, 2H), 3,19 (l,J=11,6, 2H), 2,43 (t,J=10,4, 2H), 2,34-of 2.21 (m, 2H), 2,08 was 1.69 (m, 8H).

Example 446

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-he

Specified in the title compound was obtained from the compound of example 253, step D, in accordance with the procedure described in example 254, step D. Mass spectrum (ESI): mass calculated for C23H25N3About3S, 423,16; m/z found 424,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,80 (l,J=8,1, 1H), 7.68 per to 7.62 (m, 3H), 7,53-7,49 (m, 2H), 7,42 (t,J=8,1, 1H), 7,32 (t,J=8,3, 1H), of 4.44 (t,J=6,3, 1H), to 4.38 (s, 2H), 4,25-to 4.15 (m, 1H), 3,68 is 3.57 (m, 3H), 3.33 and-3,13 (m, 3H), 2,71 (DD,J=10,9, 6,3, 1H), 2,28 (t,J=17,7, 1H), 2,13-2,02 (m, 2H), 2,01-of 1.92 (m, 2H).

Example 447

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-g is proximinality-2-he

Specified in the title compound was obtained from the compound of example 253, step D, in accordance with the procedure described in example 254, step D. Mass spectrum (ESI): mass calculated for C23H25N3About3S, 423,16; m/z found 424,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,80 (l,J=8,1, 1H), 7.68 per to 7.62 (m, 3H), 7,53-7,49 (m, 2H), 7,42 (t,J=8,1, 1H), 7,32 (t,J=8,3, 1H), of 4.44 (t,J=6,3, 1H), to 4.38 (s, 2H), 4,25-to 4.15 (m, 1H), 3,68 is 3.57 (m, 3H), 3.33 and-3,13 (m, 3H), 2,71 (DD,J=10,9, 6,3, 1H), 2,28 (t,J=17,7, 1H), 2,13-2,02 (m, 2H), 2,01-of 1.92 (m, 2H).

Example 448

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using trimethylsilyltriflate. Mass spectrum (ESI): mass calculated for C20H22N4About2S, 382,15; m/z found 383,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=7,8, 1H), 7,63 (l,J=7,8, 1H), 7,40-7,33 (m, 3H), 7,30-7,21 (m, 3H), of 5.82 (d,J=7,8, 1H), 5,10 (l,J=4,6, 1H), 3,84 (s, 1H), 3,56 (Sirs, 1H), 3,49 (s, 2H), 2,81 (l,J=11,6, 2H), 2,12 (t,J=11,1, 2H), 1,90 (l,J=11,9, 2H), 1,51-of 1.39 (m, 2H).

Example 449

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}Arslanova acid

Specified in the title compound was obtained from the compound of example 443 in accordance with the procedure described in example 433, with the adiya C. Mass spectrum (ESI): mass calculated for C21H21N3About4S, 411,13; m/z found 412,3 [M+H]+.1H NMR (400 MHz, CD3OD): 7,78 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H), 7,55 is 7.50 (m, 2H), 7,44 and 7.36 (m, 3H), 7,31 (t,J=8,1, 1H), 3,84 (s, 2H), 3,81-and 3.72 (m, 1H), 3,11 (l,J=10,9, 2H), 2,59-2,47 (m, 2H), 2.00 in at 1.91 (m, 2H), 1,79-of 1.66 (m, 2H).

Example 450

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido

Specified in the title compound was obtained in accordance with the procedure described in example 431, using glycolic acid. Mass spectrum (ESI): mass calculated for C21H23N3About3S, 397,15; m/z found 398,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=7,8, 1H), 7,65 (l,J=8,1, 1H), 7,40-7,35 (m, 3H), 7,31-of 7.23 (m, 3H), 6,83 (l,J=8,1, 1H), 5,33, (Sirs, 1H), 3,99 (s, 2H), a 3.87 of 3.75 (m, 1H), 3,50 (s, 2H), 2,85 (l,J=11,4, 2H), and 2.14 (t,J=10,9, 2H), 1,92 (l,J=12,6, 2H), 1.56 to USD 1.43 (m, 2H).

Example 451

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-triptorelin

Specified in the title compound was obtained in accordance with the procedure described in example 431, using triperoxonane acid. Mass spectrum (ESI): mass calculated for C21H20F3N3O2S, 435,12; m/z found 436,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,3, 2H), 7,54 (e,J=8,6, 2H), 7,47 (is, J=8,8, 2H), 7,41 (t,J=8,3, 1H), 7,34-7,28 (m, 1H), 4,24 (s, 2H), 4,15-was 4.02 (m, 1H)and 3.59 (d,J=12,1, 2H), 3,40, (Sirs, 1H), 2,87 (t,J=11,9, 2H), 2,22-2,02 (m, 4H).

Example 452

2-[4-(1,1-dioxo-1/6-thiomorpholine-4-ylmethyl)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 251, using thiomorpholine-1,1-dioxide. Mass spectrum (ESI): mass calculated for C18H18N3O3S2, 374,08; m/z found 375,2 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), to 7.67 (d,J=8,1, 1H), 7,42-7,31 (m, 5H), 7,27 (t,J=7,8, 1H), 3,66 (s, 2H), 3,03 (l,J=26,3, 8H).

Example 453

Tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, using tert-butyl ether N-(sulphonylchloride)carbamino acid. Mass spectrum (ESI): mass calculated for C24H30N4O5S2, 518,17; m/z found 519,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,2, 1H), to 7.67 (d,J=8,2, 1H), 7,42-7,35 (m, 3H), 7,34-7,24 (m, 3H), 5,18 (Sirs, 1H), 3,55(with,2H), 3,39-3,29 (m, 1H), 2,83 (l,J=11,7, 2H), 2,31-to 2.18 (m, 2H), 1,98 (l,J=11,7, 2H), 1,72-to 1.59 (m, 2H), 1,47 (s, 9H).

Example 454

<> N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using acetylchloride. Mass spectrum (ESI): mass calculated for C21H23N3O2S, 381,15; m/z found 382,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=7,8, 1H), to 7.67 (d,J=8,1, 1H), 7,43 and 7.36 (m, 3H), 7,33-7,24 (m, 3H), 5,65 (Sirs, 1H), a 3.87 is 3.76 (m, 1H), 3,54 (s, 2H), 2,86 (l,J=12,1, 2H), 2,17 (t,J=11,4, 2H), 1,97(8, 3H), 1.93 and (l,J=11,9, 2H), 1.56 to the 1.44 (m, 2H).

Example 455

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfone

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using N,N-dimethylsulfoxide. Mass spectrum (ESI): mass calculated for C21H26N4O3S2, 446,14; m/z found 447,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,41-7,35 (m, 3H), 7,32-of 7.23 (m, 3H), 4,37 (l,J=7,8, 1H), 3,49(with,2H), 3,28-3,17 (m, 1H), 2,81 (l,J=10,9, 2H), 2,78(with,6H), 2,11 (t,J=11,1, 2H), 1,98 (l,J=10,9, 2H), 1,61 of 1.50 (m, 2H).

Example 456

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-atilmotin

Specified in the title compound was obtained in accordance with the method described in examples is e 253, stage, using utilizationof. Mass spectrum (ESI): mass calculated for C22H26N4O2S, 410,18; m/z found 411,5 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,42-7,34 (m, 3H), 7,32-of 7.23 (m, 3H), 4,54 (Sirs, 1H), 4,45 (l,J=7,6, 1H), 3,67-3,55 (m, 1H), 3,50 (s, 2H), 3,23-3,14 (m, 2H), 2,80 (l,J=11,9, 2H), 2.13 in (t,J=11,4, 2H), 1.93 and (l,J=12,6, 2H), 1,48-of 1.36 (m, 2H), 1.12 in (t,J=7,3, 3H).

Example 457

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using ethylisothiocyanate. Mass spectrum (ESI): mass calculated for C22H26N4OS2, 426,15; m/z found 427,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=7,8, 1H), to 7.67 (d,J=8,1, 1H), 7,41-7,34 (m, 3H), 7,32-7,24 (m, 3H), 6,03 (Sirs, 1H), 5,74 (Sirs, 1H), 4,20-4,00 (m, 1H), 3,51 (s, 2H), 3,47-to 3.35 (m, 2H), 2,82 (l,J=11,6, 2H), 2.05 is (t,J=11,1, 2H), 2.05 is (l,J=11,9, 2H), 1,57-of 1.45 (m, 2H), 1,21 (t,J=7,3, 3H).

Example 458

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using 1-propanesulfonate. Mass spectrum (ESI): mass calculated for C22/sub> H27N3O3S2, 445,15; m/z found KZT 446.4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,40-7,34 (m, 3H), 7,32-7,22 (m, 3H), 4,85 (l,J=8,1, 1H), 3,48 (s, 2H), 3,36-3,24 (m, 1H), 3,02-to 2.94 (m, 2H), 2,81 (l,J=11,9, 2H), 2,11 (t,J=10,6, 2H), 1,95 (l,J=12,6, 2H), 1,89-of 1.78 (m, 2H), 1,65-and 1.54 (m, 2H), 1,04 (t,J=7,3, 3H).

Example 459

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using 2-propanesulfinamide. Mass spectrum (ESI): mass calculated for C22H27N3O3S2, 445,15; m/z found KZT 446.4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,41-7,35 (m, 3H), 7,32-7,24 (m, 3H), 3,79 (l,J=5,6, 1H), 3,51 (s, 2H), 3,38-of 3.27 (m, 1H), 2,89-2,78 (m, 2H), 2,19-of 1.94 (m, 5H), 1,76 (l,J=30,8, 6H), 1,69-of 1.55 (m, 2H).

Example 460

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide

Specified in the title compound was obtained from the compound of example 453 in accordance with the procedure described in example 253, step C. Mass spectrum (ESI): mass calculated for C19H22N4About3S2, 418,11; m/z found 419,4 [M+H]+.1H NMR (400 MHz, CDCl3): is 10.68 (Sirs, 1H), 7,60 (l,J=8,3, 1H), 7,56 (l,J=8,3, 1H, of 7.48-7,38 (m, 2H), 7,32-7,24 (m, 3H), 7,18 (t,J=7,8, 1H), 6,24 (Sirs, 2H), 4,10 (s, 2H), 3,80-3,66 (m, 1H), 3,57-3,10 (m, 2H), 3.04 from-2,61 (m, 2H), 2,41-to 1.61 (m, 4H).

Example 461

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide

Specified in the title compound was obtained in accordance with the procedure described in example 431, using formic acid. Mass spectrum (ESI): mass calculated for C20H21N3O2S, 367,14; m/z found 368,4 [M+H]+.1H NMR (400 MHz, CDCl3): to 12.28 (Sirs, 1H), 7,73 (l,J=7,8, 1H), 7.68 per (e,J=7,8, 1H), 7,47-7,24 (m, 6H), 6,33 (l,J=7,3, 1H), 4,05-of 3.94 (m, 1H), 3,80 (s, 2H), 3,14 (l,J=11,6, 2H), 2,41 (t,J=11,9, 2H), 1,99 (l,J=13,1,2H), 1,83 is 1.70 (m, 2H).

Example 462

Ethyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using ethylchloride. Mass spectrum (ESI): mass calculated for C22H25N3O3S, 411,16; m/z found 412,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,41-7,34 (m, 3H), 7,32-7,22 (m, 3H), 4,62 (Sirs, 1H), 4,10 (DD,J=7,3, 6,8, 2H), 3,59-3,51 (m, 1H), 3,49 (s, 2H), 2,80 (l,J=11,6, 2H), 2,12 (t,J=11,6, 2H), 1.93 and (l,J=12,1, 2H), 1,51-of 1.39 (m, 2H), 1,23 (t,J=7,1,3H).

Example 463

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using propionitrile. Mass spectrum (ESI): mass calculated for C22H25N3O2S, 395,17; m/z found 396,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,41-7,34 (m, 3H), 7,32-7,22 (m, 3H), 5,61 (l,J=8,1, 1H), a 3.87 is 3.76 (m, 1H), 3,49 (s, 2H), 2,82 (l,J=11,9, 2H), 2,22-2,07 (m, 4H), 1,90 (l,J=13,1, 2H), 1,51-of 1.39 (m, 2H), 1.14 in (t,J=7,6, 3H).

Example 464

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using butyrylcholine. Mass spectrum (ESI): mass calculated for C23H27N3O2S, 409,18; m/z found 410,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,40-7,35 (m, 3H), 7,31-of 7.23 (m, 3H), 5,64 (l,J=8,1, 1H), a 3.87-of 3.77 (m, 1H), 3,49 (s, 2H), 2,81 (l,J=11,6, 2H), 2,16-2,07 (m, 4H), 1.91 a (l,J=12,9, 2H), 1,71 is 1.60 (m, 2H), 1,51-of 1.39 (m, 2H), 0,93 (t,J=7,3, 3H).

Example 465

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-proprotein

Specified in the title compound was obtained in accordance with the methodology described in Primera, stage, using propositionthe. Mass spectrum (ESI): mass calculated for C23H28N4O2S, 424,19; m/z found 425,5 [M+H]+.1H NMR (400 MHz, CDCl3): of 7.70 (d,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,39-7,33 (m, 3H), 7,28-7,21 (m, 3H), 5,54 (Sirs, 1H), lower than the 5.37 (d,J=8,1, 1H), 3,66 of 3.56 (m, 1H), 3,48 (s, 2H), 3,11 (DD,J=7,1, 6,8, 2H), 2,80 (l,J=11,1, 2H), 2,11 (t,J=11,1, 2H), 1.91 a (l,J=11,1, 2H), 1,54-to 1.38 (m, 4H), of 0.91 (t,J=7,3, 3H).

Example 466

Propyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using propellorhead. Mass spectrum (ESI): mass calculated for C23H27N3O3S, 425,18; m/z found 426,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,39-7,33 (m, 3H), 7,31-7,21 (m, 3H), of 4.83 (d,J=7,6, 1H), 4.00 points (t,J=6,6, 2H), to 3.58-3.49 points (m, 1H), 3,47 (s, 2H), 2,79 (l,J=11,6, 2H), 2,10 (t,J=10,9, 2H), 1.91 a (l,J=11,1, 2H), 1,67-of 1.56 (m, 2H), 1,52-of 1.40 (m, 2H), 0,92 (t,J=7,6, 3H).

Example 467

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metalmachine

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using methyl isocyanate. Mass spectrum (ESI): mass calc is fair for C 21H24N4O2S, 396,16; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,45-7,34 (m, 3H), 7,33-7,22 (m, 3H), 5,71 (Sirs, 2H), 3,69-3,59 (m, 1H), of 3.56 (s, 2H), 2,87 (l,J=11,9, 2H), 2,73 (l,J=4,8, 3H), of 2.21 (t,J=10,1, 2H), 1.93 and (l,J=10,4, 2H), 1,58-of 1.45 (m, 2H).

Example 469

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloxetane

Specified in the title compound was obtained in accordance with the procedure described in example 255, step C, using methyl isocyanate. Mass spectrum (ESI): mass calculated for C22H26N4O2S, 410,18; m/z found 411,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,41-7,34 (m, 3H), 7,31-7,22 (m, 3H), 4,63 (DD, J=4,6, 4,6, 1H), 4,21-4,11 (m, 1H), 3,49 (s, 2H), 2,93 (l,J=11,9, 2H), 2,79 (l,J=4,8, 3H), 2,71 (s, 3H), 2,08 (t,J=11,9, 2H), 1,76-of 1.64 (m, 2H), 1,63-and 1.54 (m, 2H).

Example 470

1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metalmachine

Specified in the title compound was obtained in accordance with the procedure described in example 255, step C, using trimethylsilyltriflate. Mass spectrum (ESI): mass calculated for C21H24N4O2S, 396,16; m/z found 397,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,42-7,34 (m, 3H), 7,32-7,21 (m, 3H), 493 (, 2H), 4,16-a 4.03 (m, 1H), 3,50 (s, 2H), 2,94 (l,J=11,4, 2H), was 2.76 (s, 3H), 2,09 (t,J=11,4, 2H), 1,79-of 1.66 (m, 2H), 1,65-of 1.56 (m, 2H).

Example 471

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide

Specified in the title compound was obtained in accordance with the procedure described in example 255, step C, using acetylchloride. Mass spectrum (ESI): mass calculated for C22H25N3O2S, 395,17; m/z found 396,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,65 (l,J=8,1, 1H), 7,41-7,34 (m, 3H), 7,31-7,22 (m, 3H), 4,55-of 4.44 (m, 1H), 3,49 (s, 2H), 3,01-2,90 (m, 2H), 2,84 (s, 3H), 2,15-of 2.09 (m, 2H), 2,07 (s, 3H), 1.77 in-of 1.65 (m, 2H), 1,64-of 1.53 (m, 2H).

Example 472

Methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid

Specified in the title compound was obtained in accordance with the procedure described in example 255, step C, using methylcarbamate. Mass spectrum (ESI): mass calculated for C21H25N3O3S, 411,16; m/z found 412,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,42-7,35 (m, 3H), 7,33-7,24 (m, 3H), 4,16-of 3.96 (m, 1H), 3,69 (s, 3H), 3,51 (s, 2H), 2.95 and (l,J=11,4, 2H), 2,78 (s, 3H), 2,08 (t,J=10,9, 2H), 1,82 was 1.69 (m, 2H), 1,65-of 1.57 (m, 2H).

Example 473

Methyl ester of N-{1-[4-(benzothiazol-2-yloxy)b is nil]piperidine-4-yl}-N-methoxylamine acid

Specified in the title compound was obtained in accordance with the procedure described in example 255, step C, using methyl ester Chlorococcales acid. Mass spectrum (ESI): mass calculated for C23H25N3O4S, 439,16; m/z found 440,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,73 (l,J=8,1, 1H), 7,66 (l,J=8,1, 1H), 7,41-7,34 (m, 3H), 7,33-of 7.23 (m, 3H), to 4.41-4,32 (m, 1H), a 3.87 (s, 3H), 3,51 (s, 2H), 2,97 (l,J=11,9, 2H), 2,88 (s, 3H), 2.13 in (t,J=11,9, 2H), 1,95 of-1.83 (m, 2H), 1,72-of 1.62 (m, 2H).

Example 474

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylocella acid

Specified in the title compound was obtained from the compound of example 473 in accordance with the procedure described in example 433, step C. Mass spectrum (ESI): mass calculated for C22H23N3About4S, 425,14; m/z found 426,3 [M+H]+.1H NMR (400 MHz, CDCl3): to 7.68 (d,J=8,1, 1H), to 7.59 (d,J=8,1, 1H), 7,37-7,28 (m, 3H), 7,27-7,16 (m, 3H), 4,27-4,16 (m, 1H), 3.43 points (s, 2H), 2,93 (l,J=11,897, 2H), 2,75 (s, 3H), 2,01 (t,J=11,9, 2H), 1,82-of 1.65 (m, 2H), 1,58 to 1.47 (m, 2H).

Example 475

N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine

A. 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-illinoid.

To a suspension of 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine (339 mg, 1.0 mmol) in CH3HE (2.0 ml) was added the sodium acetate (180 mg, 2.2 mmol) at room temperature. The suspension turned into a clear solution. Then the solution was cooled to 0°C. was added dropwise brazian (159 mg, 1.5 mmol) in CH3HE (0.7 ml). The reaction mixture was stirred at 5°C for 2 h and then at room temperature overnight. The mixture was filtered through a funnel with a Frit, the filtrate was absorbed on silica gel (40 g) and purified (0-10% CH3HE/CH2Cl2) to obtain the volatile oil (123 mg, yield 34%). Mass spectrum (ESI): mass calculated for C20H20N2OS; 364,14; m/z found 365,3 [M+H]+.

C. N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine.

To a solution of 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ellenabad (123 mg, 0.34 mmol) in DMF (2 ml) in small portions was added hydroxylamine hydrochloride (41,5 mg to 0.60 mmol) and then sodium carbonate (119 mg, 1.12 mmol). The reaction mixture was stirred at room temperature for 2 h and was distributed between EtOAc (20 ml) and H2O (20 ml). The organic phase is washed with saturated salt solution, dried and concentrated under reduced pressure to obtain the crude product as a light solid. The crude product was purified on SIO, SIS2(12 g, 0-10% CH3HE/CH2Cl2with getting solid white (117 mg, yield 86%). Mass spectrum (ESI): mass calculated for C 20H23N5O4S; 397,16; m/z found 398,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,38-to 7.32 (m, 3H), 7,28-7,21 (m, 3H), 4,69 (Sirs, 2H), 3.46 in (s, 2H), 3.27 to and 3.16 (m, 1H), 2,78 (l,J=10,9, 2H), 2,04 (t,J=11,1, 2H), 1,92 (l,J=11,1, 2H), 1,51-to 1.38 (m, 2H).

Example 476

Isopropyl ester N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using isopropylmalate. Mass spectrum (ESI): mass calculated for C23H27N3O3S, 425,18; m/z found 426,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7,63 (l,J=8,1, 1H), 7,38-7,33 (m, 3H), 7,31-7,21 (m, 3H), 4.95 points-is 4.85 (m, 1H), 4.75 in (q,J=7,1, 1H), to 3.58-3.49 points (m, 1H), 3,47 (s, 2H), 2,79 (l,J=11,6, 2H), 2,09 (t,J=11,4, 2H), 1.91 a (l,J=11,9, 2H), 1,50-of 1.39 (m, 2H), 1,21 (l,J=6,5, 6H).

Example 477

3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloxetane

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using N,N-dimethylammoniumchloride. Mass spectrum (ESI): mass calculated for C22H26N4O2S, 410,18; m/z found 411,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,71 (l,J=8,1, 1H), to 7.64 (d,J=8,1, 1H, 7,39-7,33 (m, 3H), 7,30-7,21 (m, 3H), to 4.41 (d,J=7,8, 1H), of 3.73-3,62 (m, 1H), 3,48 (s, 2H), 2,87 (s, 6H), 2,81 (l,J=11,6, 2H), 2,11 (t,J=11,9, 2H), 1.93 and (l,J=11,6, 2H), 1,50-to 1.38 (m, 2H).

Example 478

{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ether acetic acid

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using chlorocarbonate ester of acetic acid. Mass spectrum (ESI): mass calculated for C23H25N3O4S, 439,16; m/z found 440,4 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (d, J=7,8, 1H), 7,65 (d, J=8,1, 1H), 7,40-7,35 (m, 3H), 7,32-of 7.23 (m, 3H), 6,11 (d, J=8,3, 1H), 4,53, (s, 2H), 3,93-3,82 (m, 1H), 3,50 (s, 2H), and 2.83 (d, J=11,9, 2H), of 2.15 (s, 3H), and 2.14 (t, J=11,9, 2H), 1,93 (d, J=12,1,2H), 1.56 to a 1.45 (m, 2H).

Example 479

{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea

A. 1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-benzoylthiophene.

Specified in the title compound was obtained in accordance with the procedure described in example 253, step C, using benzoylisothiocyanate. Mass spectrum (ESI): mass calculated for C27H26N4O2S2, 502,15; m/z found 503,3 [M+H]+.1H NMR (400 MHz, CDCl3): 10,80 (l,J=8,1, 1H), 9,06(with,1H), 7,81 (l,J=8,3, 2H), 7,72 (l,J=8,3, 1H), 7,65 (l,J=7,8, 1H), to 7.59 (t,<> J=7,6, 1H), 7,50 was 7.45 (m, 2H), 7,42-7,34 (m, 3H), 7,33-7,22 (m, 3H), 4,40-the 4.29 (m, 1H), 3,53 (s, 2H), 2,80 (l,J=11,1, 2H), 2.26 and (t,J=10,1, 2H), 2,12 (l,J=11,9, 2H), 1,76-of 1.64 (m, 2H).

Century {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea.

To 1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-benzoylthiophene (300 mg, of 0.60 mmol) was added 10% aqueous sodium hydroxide (10 ml). The reaction mixture is boiled under reflux for 1 h the Obtained white suspension was cooled to room temperature and was extracted with 10% CH3HE/CH2Cl2(3×50 ml). The organic layer was dried (Na2SO4) and concentrated under reduced pressure to get crude product in the form of not-quite-white solid. The crude product was purified on SIO, SIS2(40 g; 0-10% CH3HE/CH2Cl2) obtaining specified in the connection header in the form of a solid white color (219 mg, yield 92%). Mass spectrum (ESI): mass calculated for C20H22N4OS2; 398,12; m/z found 399,3 [M+H]+.1H NMR (400 MHz, CDCl3): 7,72 (l,J=8,1, 1H), 7.68 per (e,J=8,1, 1H), 7,42 and 7.36 (m, 3H), 7,34-7,26 (m, 3H), 6,09 (m, 1H), 4,29-was 4.02 (m, 1H), only 3.57 (s, 2H), 2,88 (l,J=11,1, 2H), 2,29 (s, 2H), 2,20 (t,J=11,1, 2H), 2,04 (l,J=10,1, 2H), 1.60-to a 1.45 (m, 2H).

Example 480

(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol

Specified in the header is the connection received in accordance with the methodology described in example 37, using piperidine-4-ylmethanol. Mass spectrum (ESI): mass calculated for C21H25N3O3, 367,19; m/z found 368,4 [M+H]+.1H NMR (400 MHz, DMSO-d6): 12,24 (s, 1H), 7,32 (s, 2H), 7,27 (l,J=8,9, 2H), was 7.08 (s, 2H), 7,00 (l,J=8,9, 2H), to 4.41 (s, 1H), 4.09 to (s, 2H), 3,24 (s, 2H), 2,92 (l,J=11,1, 2H), 2,68 (s, 2H), 1,98 (t,J=11,6, 2H), 1,62 (l,J=11,6, 2H), 1,24 (Sirs, 1H), 1,11 (l,J=9,2, 2H).

Example 481

2-[4-(2-morpholine-4-ylethoxy)phenoxy]benzooxazol

Specified in the title compound was obtained in accordance with the procedure described in example 11, using 4-(2-chloroethyl)of the research. Mass spectrum (ESI): mass calculated for C19H20N2O4, 340,14; m/z found 341,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=7,1, 1H), 7,42 (l,J=7,2, 1H), was 7.36-7,30 (m, 2H), 7,29-7,20 (m, 2H), 7.03 is-to 6.95 (m, 2H), 4,14 (t,J=5,7, 2H), 3,80-and 3.72 (m, 4H), and 2.83 (t,J=5,7, 2H), 2,60 (t,J=4,6, 4H).

Example 482

2-[4-(2-morpholine-4-ylethoxy)phenoxy]benzothiazole

Specified in the title compound was obtained in accordance with the procedure described in example 12 using 4-(2-chloroethyl)research and 2-chlorobenzothiazole. Mass spectrum (ESI): mass calculated for C19H20N2O3S, 356,24; m/z found 341,1 [M+H]+.1H 6.12 NMR (400 MHz, CDCl3): 7,74 (l,J=7,6,1H), 7,66 (l,J=7,3, 1H), 7,39 (t,J=7,3, 1H), 7,31-7,20 (m, 3H), 7,00-6,93 (m, 2H), 4,14 (t,J=5,7, 2H), 3,80-and 3.72 (m, 4H), and 2.83 (t,J=5,7, 2H), 2,60 (t,J=4,6, 4H).

Example 483

2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzothiazole.

Specified in the title compound was obtained in accordance with the procedure described in example 12 using 4-(2-chloroethyl)piperidine and 2-chlorobenzothiazole. Mass spectrum (ESI): mass calculated for C20H22N2O2S, 354,14; m/z found 355,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,74 (l,J=8,1, 1H), 7,65 (l,J=8,0, 1H), 7,39 (t,J=7,3, 1H), 7,30-7,22 (m, 3H), 7,00-6,92 (m, 2H), 4,13 (t,J=6,0, 2H), 2,81 (t,J=6,0, 2H), 2,58-2,48 (Sirs, 4H), 1,68 is 1.58 (m, 4H), 1,52-of 1.42 (m, 2H).

Example 484

{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}diethylamin

Specified in the title compound was obtained in accordance with the procedure described in example 11, using (2-chloroethyl)diethylamine. Mass spectrum (ESI): mass calculated for C19H22N2O3, 326,16; m/z found 327,1 [M+H]+.1H NMR (400 MHz, CDCl3): 7,51 (l,J=7,6, 1H), 7,42 (l,J=7,2, 1H), was 7.36-7,29 (m, 2H), 7,28-7,19 (m, 2H), 7,02-6,94 (m, 2H), 4,07 (t,J=6,3, 2H), 2,90 (t,J=6,3, 2H), 2,65 (kV,J=7,2, 4H), of 1.09(t,J=7,1, 6H).

Methods of analysis

The following illustrates the results of the analyses that were conducted for cenciarini of the present invention.

Analysis of recombinant human L4-hydrolases activity inhibitor L4-hydrolases

Compounds of the present invention were tested for their inhibitory activity against recombinant human L4-hydrolases (rhLTA4H). Received vectors used for expression rhLTA4H, mainly as follows: DNA encoding L4-hydrolase, amplified using polymerase chain reaction (PCR), where the matrix used a cDNA library of human placenta. Oligonucleotide primers for PCR reactions were designed based on the 5'-end and the complement of the 3'-end of the known nucleotide sequence of the coding region of the human gene L4-hydrolases (C.D. Funk et al., Proc. Natl. Acad. Sci., USA, 1987, 84:6677-6681). Amplificatory 1,9 TPN DNA fragment encoding L4-hydrolase, was isolated and cloned into the pFastBac1 vector (Invitrogen). Recombinant baculovirus was generated in accordance with the manufacturer's instructions and used to infect cellsSpodoptera frugipedra(Sf-9). The recombinant enzyme L4-hydrolase was isolated from infected cells, Sf-9, mainly, as described J.K. Gierse et al. (Protein Expression and Purification 1993, 4:358-366). The purified enzyme solution was adjusted so that it contained 0,29 mg/ml L4-hydrolases, 50 mm Tris (pH 8.0), 150 mm Nl, 5 mm dithiothreitol, 50% glycerol, and a cocktail on the tion of a set of protease inhibitors, not containing EDTA (Roche). The specific activity of the enzyme was approximately 3.8 ámol/min/mg.

The substrate L4 was obtained from methyl ester L4 (Cayman Chemical) by processing 67 equivalents Paon in nitrogen atmosphere at room temperature for 40 minutes. The substrate L4 in the form of the free acid was frozen at -80°C and stored until use. Each compound was diluted to various concentrations in analytical buffer (0,1M potassium phosphate (pH 7.4), 5 mg/ml SA, without fatty acids), containing 10% DMSO. a 25 µl aliquot of each dilution of the compounds were incubated for 10 minutes at room temperature with an equal volume of analytical buffer containing 36 ng of recombinant human L4. Then the solution was brought up to 200 μl analytical buffer. L4 (free acid) was thawed, diluted in analytical buffer to a concentration of 357 ng/ml and then added 25 μl (9 ng) substrate L4 to the reaction mixture (total volume=225 μl) at time 0. Each reaction was carried out at room temperature for 10 minutes. The reaction was stopped by diluting 10 ál of the reaction mixture 200 Microlitre analytical buffer. LT4 quantitatively evaluated in the diluted sample using a commercially available enzyme-linked immunosorbent assay (Cayman Chemical Co.) in accordance with the manufacturer's recommendations. Each experiment Prov is conducted in accordance with routine procedures, using positive controls, which were analyzed in identical conditions, but without addition of the compound inhibitor and negative control containing all components analysis, with the exception of the enzyme. The value of the IC50were determined using the curve activity at various concentrations of the compounds constructed on a 4-parametricheskom equation using the computer program Grafit (Erithacus).

It is obvious that the value of the IC50presented in the following tables must be within the typical three-dimensional manifolds analyses of this type. The following values essentially represent the average value for 1-3 measurements.

Table 1
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1164515941
1324 1713592
14959513625
27777102712
361478348155
44892148419

Table 2
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1210017612 29815
1522180230260
1861831832512
227192332822
2311955833113
2542024334100
3117206433624
8023207163537
81 5211935745
10232141835811
104142241435948
109212252536033
11040250263618
14364251163634
14643255136639
1473325914 3806
1501261333892
153826244194
1559263543721
15672651124468
15712701644728
1611274294507
1639285764544
167 372872846227
16827288447119
16932296334797
17227294648345

Table 3
ExampleIC50(nm)ExampleIC50(nm)
3710134110
123423036
1272923118
13213948539
133111

Production LB4 in stimulated iodoform calcium mouse blood for evaluation of inhibitory activity L4

Mice CD-1 were killed and blood was collected in Eparistera syringes by cardiac puncture. The obtained blood was diluted 1:15 RPMI medium 1640 and 200 ál aliquots of the diluted blood was added to the wells of 96-well microtiter tablet. Test connection-inhibitors L4 received in various concentrations in the medium RPMI 1640 containing 1% DMSO and 20 μl of each test solution was added to the well containing diluted whole blood (final concentration of DMSO of 0.1%). The contents of the microtiter tablet incubated for 15 minutes at 37aboutWith the incubator with high humidity and then to each well sample was added calcium ionophor A ((Sigma Chemical Co., St. Louis, MO) (final concentration=20 ng/ml). Incubation was continued under the same conditions for another 10 minutes to education L4. The reaction was stopped by centrifugation (833×g, 10 minutes at 4°C) and supernatant analyzed for L4 using a commercially available kit tverdofazno the th enzyme immunoassay (Cayman Chemical Co.) in accordance with the manufacturer's instructions. Each experiment was performed in accordance with routine procedures using positive controls, which were analyzed in identical conditions, but without addition of the compound inhibitor and negative control containing all components analysis, with the exception of the enzyme. The value of the IC50were determined using the curve activity at various concentrations of the compounds constructed on a 4-parametricheskom equation using the computer program Grafit (Erithacus).

Table 4
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1144271439472
13414423481264
148946 2948411

446
Table 5
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1525125099328143
181621983933185
2212320643334453
239320781336153
8141251159359
1025525949360246
1045202618138017
10918926349437105
15052274331446131
15512728857447240
1562000296133462144
16110029869483161
180 15302212

Table 6
ExampleIC50(nm)ExampleIC50(nm)
127376133290
132347134436

Murine model of inflammation induced by arachidonic acid

Connection-inhibitors L4 of the present invention was diluted with a mixture of 20% cyclodextrin/H2O at a concentration of 3 mg/ml of the resulting solution through a gastric tube was administered to female mice Balb/C weighing approximately 20 grams each (0.2 ml/mouse, 30 mg L4-inhibiting compound per kg of body weight). After 60 minutes after administration L4 inhibitor each mouse was treated by applying 20 μl of arachidonic acid (100 mg/ml in acetone) on the left ear and 20 μl of one of acetone on the right ear. After 3 hours, mice were killed, blood was collected in heparinized syringes and ear took a biopsy 8 is m The ear biopsies were weighed to determine the level of swelling, then frozen at -80°C and stored until analysis at the influx of neutrophils.

100 µl aliquots of heparinized blood was added to the wells of the microtiter tablet together with an equal volume of RPMI medium 1640 and in each sample well was added calcium ionophor A (final concentration=20 ng/ml). The contents of the microtiter tablet incubated for 10 minutes at 37aboutC. the Reaction was stopped by centrifugation (833×g, 10 minutes at 4°C). Supernatant analyzed for L4 using a commercially available kit enzyme-linked immunosorbent assay (Cayman Chemical Co.) in accordance with the manufacturer's instructions. The percentage of inhibition ofex vivostimulated production L4 (% ing. L4) was determined by comparison with the animals treated in a similar way, except that the solution was injected through the gastric tube did not contain connection inhibitor.

The influx of neutrophils was assessed by measuring the activity of myeloperoxidase (MPO), neutrophil-specific enzyme. Ear biopsies homogenized in 0.5 ml of buffer for extraction (0.3 m sucrose, 0,22% (mass/about) hexadecyldimethylamine ammonium (BECOMING) and 2.5 mm citrate, obtained from a 0.5 m stock solution of citrate (pH 5.0)). Debris was removed by centrifuge the Finance at 14000×g for 10 minutes. 10 µl aliquots of the resulting supernatant were added to the wells of the microtiter tablet with 90 μl of the aliquot dilution buffer (10 mm citrate, 0,22% BECOMING) and then added 20 μl of liquid substrate system (TMB) (Sigma Chemical Co.) The contents of the microtiter tablet kept at room temperature for 1 hour. The reaction was stopped by adding 100 μl of 1M H2SO4in each sample well and myeloperoxidase activity in each sample was determined on the basis of the optical density at 405 nm. For each animal, the background value obtained for the right ear, processed by only one acetone, subtracted from the values obtained for the left ear, treated with arachidonic acid. The percentage inhibition of the influx of neutrophils (% ing. LRO) compounds of the present invention was determined by comparison with the percentage of inhibition obtained for animals treated similarly, except that these animals through the gastric tube was introduced a solution which did not contain the compound inhibitor.

Table 7
Example% ing. LTB4% ing. MPO
11 8395
148156
275072

78
Table 8
Example% ing. LTB4% ing. MPOExample% ing. LTB4% ing. MPO
1532292517966
1878832599574
227979263019
2367842749387
81833257667
1095144336670
15081913608788
15596933618690
18087874466443
25080944479048
20667764719089
2508094

Although in the description of the present invention illustrated certain details of its implementation, however, experts in this field will be obvious that the present invention can have countless variations, applications, modifications and additions which may be made in accordance with the basic principles of the present invention, and which should not deviate from the essence and scope of the invention. It should be noted that the above description is given only for illustrative purposes and is not limited to the specific form or order of presentation of parts disclosed and illustrated in this specification.

1. A method of treating or preventing LTA4H-mediated condition in a subject, introducing to the subject a therapeutically effective amount of at least one LTA4H modulator selected from compounds of the formula (II)

or their enantiomers, racemate or pharmaceutically acceptable salts
where X is selected from the group consisting of NR5, O and S, where R5represents one of N and CH3;
Y represents O;
Z is selected from the group consisting of O and communication;
W is selected from the group consisting of CH2and CHR1-CH2where R1represents H or HE, and where associated with R 1carbon group in the specified CHR1-CH2not directly linked to the nitrogen atom is linked to the specified W;
R4selected from the group consisting of H, och3and Cl;
R6represents H or F; and
R2'and R3'each independently selected from the group consisting of:
A) H, C1-7of alkyl, C3-7cycloalkyl,3-7cycloalkyl-C1-7of alkyl, where each of the substituents (a) are independently substituted by 0 or 1 RQwhere each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;
B) Deputy HetRa;
C) -C1-7alkyl-C(O)Rx;
N) -C0-4alkyl-Ar5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group >NRYand 0 or 1 additional heteroatom-N=, and optionally contains two carbonyl groups, and optionally benzododecinium;
I) -C0-4alkyl-Ar5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom;
M) SO2C1-4of alkyl;
alternative, R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified attached to the first nitrogen atom, where the specified heterocyclic ring selected from the group consisting of
i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY, -CN, -C(O)RY- 0-4alkyl-CO2RY,
-C0-4alkyl-C(O)CO2RY-C0-4alkyl-ORY- 0-4alkyl-C(O)NRYRz-,
-C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY,
-C0-4alkyl-NRYCO2RY,
-C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ-NRYC(O)CO2RY,
-C0-4alkyl-NRWSO2RY,
1,3-dehydrobenzperidol-2-on-1-Il,
1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-Il,
-C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY,
-C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen,,and;
ii) a 5-7 membered heterocyclic ring HetRchaving one additional heteroatom, otdalin the th from the specified attached nitrogen at least one carbon atom, where specified additional heteroatom selected from the group consisting of O, S(=O)2and >NRMwhere specified 5-7-membered heterocyclic ring HetRCis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RYand RZ;
iii) one of the 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as-C0-4alkyl-RZ- 0-4alkyl-CO2RYand
iv) one of the benzimidazole-1-Il,
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl} piperidine-1-Il,
4-{[(2-aminocyclohexanol)amino]methyl}piperidine-1-Il,
9-Il-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
4-oxo-1-phenyl-1,3,8-traseiro[4.5]Dec-8-yl, and
where the Deputy HetRarepresents a 6-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas heteroatom, where said heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;
RKselected from the group consisting of H and-C1-4of alkyl;
RLselected from the group consisting of-CO2RS;
RS/sup> represents hydrogen;
RMselected from the group consisting of RZ, -C(O)RY;
RNselected from the group consisting of co3, Cl, F, Br, I, HE, NH2CN, CF3CH3and NO2;
RQselected from the group consisting of-CN, -C0-4alkyl-ORY-C0-4alkyl-CO2RY- 0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY;
RWselected from the group consisting of RY;
RXselected from the group consisting of-ORY, -NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;
RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1 or 2 substituents RN;
RZselected from the group consisting of RY- 1-2alkyl-CO2RY;
RArrepresents a radical having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, pyridyl and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0.1 or 2 RNor 0 1 or RL;
RAr'is a 5-6-membered ring which has 1 or 2 heteroatoms selected from GRU the dust, consisting of O, S, N and >NRYand has 0 or 2 bonds and 0 or 1 carbonyl group, where each member with a valid valence in each of these rings is independently substituted by 0 or 1 or 2 RK;
provided that
(a) at least one of the R2'and R3'is not ethyl when one of the combinations (s1), (s2), (s3) and (s4), where each of these combinations is defined as follows:
(s1): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents S;
(s2): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents NH;
(s3): R4represents N, Z represents O, W represents CH2, Y is Oh, and X represents S;
(s4): R4represents 5-chloro, Z represents O, W represents CH2, Y is CH2and X represents S;
(b) further provided that when Z is a bond, Y is CH2W represents CHR1-CH2, R1represents H and one of R2'and R3'represents 1H-imidazol-2-yl, any of the R2'and R3'selected from A1), B)-L), where (B)-L) identified above for the connection is of formula (II), and Al) consists of H, C3-7alkenyl, where the carbon atom at the specified3-7alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom in the specified quinil, which is linked to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl, and
(c) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2'and R3'is not XCG, if the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl, halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO.

2. The method according to claim 1, where at least one LTA4H modulator selected from compounds of the formula (III) R” c

or their enantiomers, racemate or pharmaceutically acceptable salts, where
X is selected from the group consisting of NR5, O and S, where R5represents one of N and CH 3;
Y represents O;
Z is selected from the group consisting of O and communication;
W is selected from the group consisting of CH2and CHR1-CH2where R1represents H or HE, and where associated with R1carbon group in the specified CHR1-CH2not directly linked to the nitrogen atom is linked to the specified W;
R4selected from the group consisting of H, och3and Cl;
R6represents H or F; and
R2"and R3"each independently selected from the group consisting of:
A) H, C1-7of alkyl, C3-7cycloalkyl,3-7cycloalkyl-C1-7of alkyl, where each of the substituents (a) are independently substituted by 0 or 1 RQwhere each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;
B) Deputy HetRa
C) -C1-7alkyl-C(O)Rx;
N) -C0-4alkyl-Ar5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group >NRYand 0 or 1 additional heteroatom-N=, and optionally contains two carbonyl groups, and optionally benzododecinium;
I) -C0-4alkyl-Ar5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom;
M) SO2C1-4of alkyl;
al is ernative, R2"and R3"taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the attached nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of
i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY, -CN, -C(O)RY- 0-4alkyl-CO2RY,
-C0-4alkyl-C(O)CO2RY- 0-4alkyl-ORY- 0-4alkyl-C(O)NRYRz-,
-C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY,
-C0-4alkyl-NRYCO2RY,
-C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY,
-C0-4alkyl-NRWSO2RY,
1,3-dehydrobenzperidol-2-on-1-Il,
1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-Il,
-C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY,
-C0-4alkyl-N(RY)(SO2)NRYCO2RY , halogen,,and;
ii) a 5-7 membered heterocyclic ring HetRchaving one additional heteroatom separated from the specified attached nitrogen at least one carbon atom, where the specified additional heteroatom selected from the group consisting of O, S(=O)2and >NRMwhere specified 5-7-membered heterocyclic ring HetRcis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RYand RZ;
iii) one of the 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as-C0-4alkyl-RZ- 0-4alkyl-CO2RY;
iv) one of the benzimidazole-1-Il,
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl} piperidine-1-Il,
4-{[(2-aminocyclohexanol)amino] methyl} piperidine-1-Il,
9-Il-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
4-oxo-1-phenyl-1,3,8-diazaspiro[4.5]Dec-8-yl, and
where the Deputy HetRarepresents a 6-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas the e heteroatoms, where the heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;
RKselected from the group consisting of H and-C1-4of alkyl;
RLselected from the group consisting of-CO2RS;
RSrepresents hydrogen;
RMselected from the group consisting of RZ, -C(O)RY;
RNselected from the group consisting of co3, Cl, F, Br, I, HE, NH2CN, CF3CH3and NO2;
RQselected from the group consisting of-CN, -C0-4alkyl-ORY- 0-4alkyl-CO2RY- 0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY;
RWselected from the group consisting of RY;
RXselected from the group consisting of-ORY, -NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;
RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1 or 2 substituents RN;
RZselected from the group consisting of RY- 1-2alkyl-CO2RY;
RArrepresents a radical having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, PI is idela and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0.1 or 2 RNor 0 1 or RL;
RAr'is a 5-6-membered ring which has 1 or 2 heteroatoms selected from the group consisting of O, S, N and >NRYand has 0 or 2 bonds and 0 or 1 carbonyl group, where each member with a valid valence in each of these rings is independently substituted by 0 or 1 or 2 RK;
provided that
(a) the R2"and R3", further satisfy one of the following conditions:
(E1): at least one of the R2"and R3"isn't C1-5the alkyl when Z represents O, and X represents S;
(E2): none of the R2"and R3"is not-C1-4alkyl-C(O)RXwhere RXrepresents one of the1-4of alkyl, HE, -OS1-4of alkyl, -OS0-4alkyl-RAror-NRYRYif Y is O, Z is a bond, and R2"differs from R3";
(E3) none of R2"and R3"is not-C1-4alkyl-CN, if Y is O, Z is a bond, and R2"differs from R3";
(b) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2about the Institute of R 2"and R3"is not XCG, if the other represents C1-6alkyl, where XCG is a group

where HC16 represents one of H, C1-6of alkyl,
halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO.

3. The method according to claim 1, where the specified R4represents N.

4. The method according to claim 1, where the specified R2'and R3'each independently selected from the group consisting of A), B), (C) and (I)as defined in claim 1.

5. The method according to claim 1, where the specified R2'and R3'taken together with the nitrogen atom to which they are attached, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii)as defined in claim 1.

6. The method according to claim 1, where the specified LTA4H-mediated condition is an inflammation associated with at least one disease, such as asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

7. With whom persons according to claim 1 or 2, where the specified at least one LTA4H modulator is one of the following connections:
2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzooxazol;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl }piperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dibutylamine;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol;
2-[4-(2-piperidine-1-retil)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl} cyclohexylethylamine;
1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl} piperidine-4-ol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]-2-hydroxypropyl}-4-phenylpiperidine-4-ol;
ethyl ester of 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}dimethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dimethylamine;
2-[4-(2-azepin-1 ylethoxy)phenoxy]benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
2- {4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy} benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-carbonitrile;
1-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)Etalon;
2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy} benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}butylethylamine;
2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}benzylamino)ethanol;
2-{4-[2-(4-benzylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol;
2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}propylamino)ethanol;
2-[4-(2-azetidin-1 ylethoxy)phenoxy]benzooxazol;
N-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
ethyl ester of 1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
2-{4-[3-(4-phenylpiperazin-1-yl)propoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
2-[4-(2-pyrrolidin-1-retil)phenoxy]benzoxa the ol;
2-[4-(2-azepin-1-retil)phenoxy]benzooxazol;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}dibutylamine;
1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
methyl ester 1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}-4-phenylpiperidine-4-ol;
2-[4-(3-pyrrolidin-1-ylpropyl)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}dibutylamine;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclopropanemethylamine;
1-[4-(benzooxazol-2-yloxy)phenoxy]-3-pyrrolidin-1-improper-2-ol;
1-[2-(4-benzooxazol-2-ylmethylene)ethyl]-4-phenylpiperidine-4-ol;
amide 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2-[4-(2-morpholine-4-ylethoxy)phenoxy)benzooxazol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}diethylamine;
{2-[4-(6-chlorobenzothiazole-2-yloxy)phenoxy]ethyl}diethylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-1-ylmethanone;
ethyl ester of 3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propy the OIC acid;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he;
8-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2,8-diazaspiro[4.5]Decan-1-he;
2-[4-(3-pyrrolidin-1 ipropose)phenoxy)benzothiazole;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl} piperidine-3-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-methyl-1,3-dehydrobenzperidol-2-he;
methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-(4-methylpiperazin-1-yl)methanon;
methyl ether of 1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)propionic acid;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dimethylamine;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzothiazole;
{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}dimethylamine;
2-[4-(2-azepin-1 ylethoxy)phenoxy]benzothiazole;
2-[4-(2-azepin-1 ylethoxy)phenoxy]-6-methoxybenzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
1-{2-[4-(benzodi the evils-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dibutylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipiperidine;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethoxy}-phenoxy)benzothiazole;
2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethyl}phenoxy)benzothiazole;
1-{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
2-[4-(2-pyrrolidin-1-retil)phenoxy]benzothiazole;
2-[4-(2-azepin-1-retil)phenoxy]benzothiazole;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}dibutylamine;
2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl }piperidine-3-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-carboxylic acid;
Atila the initial ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dihydroindol-2-he;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)pyrrolidin-2-he;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-2-phenylacetamide;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-2,8-diazaspiro[4.5]Decan-1-he;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-ol;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1'-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-[1,4'] bipiperidine;
2-{4-[2-(4-methylpiperazin-1-yl)ethyl]phenoxy}benzothiazole;
2-(4-{2-[4-(1-benzyl-1H-tetrazol-5-yl)piperidine-1-yl]ethoxy}phenoxy)benzothiazole;
tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl} piperidine-4-carbonyl)piperazine-1-carboxylic acid;
amide 1-[2-(4-{benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
1-{1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-yl}pyrrolidin-2-he;
1-[4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-yl]Etalon;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-tion;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)ethanol;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-the l)-1-morpholine-4-ylatason;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-2-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)acetic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl }piperidine-4-yl)carbamino acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)methanol;
methyl ether ({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylamino)acetic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-1-yl)acetic acid;
ethyl ester of 1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-chloro-N-cyclopropanesulfonyl;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}isopropylamino)propionic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ylamine;
3-[{2-[4-(benzo is eazol-2-yloxy)phenoxy]ethyl}-(1-methylpiperidin-4-yl)amino]propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}benzoylamino)propionic acid;
3-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}amino)propionic acid;
tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)piperidine-1-carboxylic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionic acid;
3-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)propionic acid;
3-[{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}(1 methylpiperidin-4-yl)amino]propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-isopropylamino)propionic acid;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1-(1-[2-(4-benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dehydrobenzperidol-2-he;
2-(4-{2-[4-(6-methylpyridin-2-yl]piperazine-1-yl]ethyl}phenoxy)benzothiazole;
2-{4-[2-(4-acanaloniidae-1-yl]ethyl]phenoxy}benzothiazole;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopentylamine)propionic acid;
3-({2-[4-(bentot the azole-2-yloxy)phenyl]ethyl}cyclobutylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}benzoylamino)propionic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-(4-hydroxyethylpiperazine-1-yl)methanon;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperazine-1-yl]metano;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperidine-1-yl]metano;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)ethanol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-1-ol;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyronitrile;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)propionic acid;
[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
3-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
2-(4-{2-[4-(4-methoxyphenyl)piperazine-1-yl]ethoxy}phenoxy)benzothiazole;
2-{4-[2-(5-piperidine-4-intersol-1-yl)ethoxy]phenoxy}benzothiazole;
(S)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl;
these are the new ester 2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarboxylic acid;
ethyl ester of 4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-carbonyl)benzoic acid;
2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarbonyl acid;
1-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-2-ol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-1,1,1-tryptophan-2-ol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionamide;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propane-1,2-diol;
2-{4-[2-(5-phenyltetrazol-2-yl)ethoxy]phenoxy}benzothiazole;
2-{4-[2-(5-phenyltetrazol-1-yl)ethoxy]phenoxy}benzothiazole;
N-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N-cyclopropyl-2-(2H-tetrazol-5-yl)ndimethylacetamide;
(S)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
(R)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
2-{4-[2-(5-methylsulfonylmethyl-2-yl)ethoxy]phenoxy}benzothiazole;
2-{4-[2-(5-methylsulfonylmethyl-1-yl)ethoxy]phenoxy}benzothiazole;
2-[4-(2-tetrazol-2-ylethoxy)phenoxy]benzothiazole;
2-[4-(2-tetrazol-1 ylethoxy)phenoxy]benzothiazole;
(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
(1S,2R)-2-{2-[4-(bentot the azole-2-yloxy)phenyl]ethylamino}cyclohexanol;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)butyric acid;
(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
hydrochloride of 2-{4-[2-(5-piperidine-4-intersol-2-yl)ethoxy]phenoxy}benzothiazole;
7-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]-4-Spiro[3-phtalic]piperidine;
ethyl ester of 1-{3-[4-(benzothiazol-2-yloxy)phenyl]propyl}piperidine-4-carboxylic acid;
hydrochloride of 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine;
2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethoxy]phenoxy)benzothiazole;
triftoratsetata salt of CIS-4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarboxylic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amide propane-2-sulfonic acid;
methyl ester of (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid;
triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)benzo is sulfonamide;
triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)methanesulfonamide;
triftoratsetata salt (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl }piperazine-1-yl)octoxynol acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)morpholine-4-ylmethanone;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-thiophene-2-ylatason;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-3-ylmethanone;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)cyclopropylmethanol;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-methoxyethanol;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2,2,2-triptoreline;
4-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-carbonyl)benzoic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-4-ylmethanone;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(5-methylpyrazine-2-yl)methanon;
(R)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(S)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-3-yl)methanon;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-hydroxyethane;
2-[2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-oxoethyl]cyclo is intanon;
triftoratsetata salt of 3-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)propionic acid;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)oxazolidin-2-he;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)morpholine-3-one;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)morpholine-3-one;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)oxazolidin-2-he;
benzylacetone 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
hydroxyamide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(S)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbamate acid;
2-{4-[2-(4-foreperiod-1-yl)ethyl]phenoxy}benzothiazole;
2-{4-[2-(4,4-deformability-1-yl)ethyl]phenoxy}benzothiazole;
(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}pyrrolidin-3-ol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)formamide;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)urea;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-phenylazomethine;
1-(1-{2-[4-(benzothiazol-2-yloxy)is enyl]ethyl}piperidine-4-yl)-3-cyano-2-methylisoleucine;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methanesulfonamide;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylguanine;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1-phenyl-1,3,8-diazaspiro[4.5]Decan-4-one;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-diazaspiro[4.5]decane-2,4-dione;
tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamate acid;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylacetamide;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylmethanesulfonamide;
methyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamoyl] acetic acid;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-ndimethylacetamide;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbonyl)methyl ester acetic acid;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)-3-(1H-imidazol-2-yl)propionic acid;
2-(4-{2-[4-(3-nitropyridine-2-yl)-[1,4]diazepan-1-yl]ethyl}phenoxy)benzothiazole;
ethyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
ethyl ester of 1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4'] bipyridinyl-4-carboxylic acid;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}qi is appropiately;
triftoratsetata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl }cyclopropylamino)-2-methylpropionic acid;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethanol;
2-[2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethoxy]ethanol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propan-1-ol;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl(3-tetrazol-1-ylpropyl)amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl(3-pyrrol-1-ylpropyl)amine;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile
(2-cyanoethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(2H-tetrazol-5-yl)propyl]amine;
3-[5-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)tetrazol-1-yl]propionitrile;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl[3-(2H-tetrazol-5-yl)propyl]amine;
(2-hydroxy-1,1-dimethylethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(1H-[1,2,4]triazole-5-yl)propyl]amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-methyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-phenyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
2-(4-{2-[4-(1-IU the Il-1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
2-(4-{2-[4-(2-methyl-2H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile;
2-(4-{2-[4-(1H-[1,2,3]triazole-4-yl]ethyl}phenoxy)benzothiazole;
ethyl ester of 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}butyric acid;
ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
2-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
1-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-he;
N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylmethyl-1,3-diamine;
methyl ester 5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentanol acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide morpholine-4-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methylsulfonate;
5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentane acid;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}isopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(be societal-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}propylamino)propyl]pyrrolidin-2-he;
ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methanesulfonamide)butyric acid;
({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)acetic acid;
ethyl ester of 6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
ethyl ester of 7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl] ndimethylacetamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isobutyramide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]benzamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-4-chlorobenzamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide;
triftoratsetata salt [3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethylcyclopropane)propyl]amide propane-2-sulfonic acid;
ethyl ester 8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-3-phenylacetone;
8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide tetrahydrofuran-2-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-2-hydroxyacetate;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
2-[4-(2-morpholine-4-ylethoxy)phenoxy]benzothiazole;
2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzothiazole;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
cyclohexylethyl {2-[4-(1-methyl-1H-benzoimidazol-2-yloxy)phenyl]ethyl}amine;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
2-[4-(2-pyrrolidin-1-retil)phenoxy]-1H-benzoimidazol;
2-[4-(2-azepin-1-retil)phenoxy]-1H-benzoimidazol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}dibutylamine;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]the Teal}piperidine-4-ol;
methyl ester 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}cyclohexylamine;
2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-[2-(4-piperidine-1-ylethoxy)phenoxy]-1H-benzoimidazol;
(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
1-[4-(2-azepin-1 ylethoxy)phenoxy]-1H-benzoimidazole;
{3-[4-(1H-benzoimidazol-2-yloxy)phenoxy]propyl]dimethylamine;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]-1H-benzoimidazol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl]dimethylamine;
2-[4-(2-morpholine-4-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1-(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he
ethyl ester of 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid.

8. The method according to claim 2, where the specified R4represents N.

9. The method according to claim 2, where these R2"and R3"each independently selected from the group consisting of A), B), (C) and (I), as defined in section 2.

10. The method according to claim 2, where these R2"and R3"taken together with the nitrogen atom to which they are attached, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii), as defined in section 2.

11. The method of claim 2, where the specified LTA4H-mediated condition is an inflammation associated with at least one disease, such as asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

12. The method of treatment, prevention or suppression of inflammation in the subject, introducing to the subject a therapeutically effective amount of at least one LTA4H modulator selected from compounds of the formula (II)

or their enantiomers, racemate or pharmaceutically acceptable salts
where X is selected from the group consisting of NR5, O and S, where R5represents one of N and CH3;
Y represents O;
Z is selected from the group consisting of O and communication;
W is selected from the group consisting of CH2and CHR1-CH2where R1represents H or HE, and where associated with R1carbon group in the specified CHR1-CH2not directly linked to the nitrogen atom is linked to the specified W;
R4selected from the group consisting of H, och3and Cl;
R6made the focus of an H or F; and
R2'and R3'each independently selected from the group consisting of:
A) H, C1-7of alkyl, C3-7cycloalkyl,3-7cycloalkyl-C1-7of alkyl, where each of the substituents (a) are independently substituted by 0 or 1 RQwhere each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;
B) Deputy HetRa;
C) -C1-7alkyl-C(O)Rx;
N) -C0-4alkyl-Ar5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group >NRYand 0 or 1 additional heteroatom-N=, and optionally contains two carbonyl groups, and optionally benzododecinium;
I) -C0-4alkyl-Ar5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom;
M) SO2C1-4of alkyl;
alternative, R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the attached nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of
i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom is, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY-CN, -C(O)RY- 0-4alkyl-CO2RY,
-C0-4alkyl-C(O)CO2RY- 0-4alkyl-ORY- 0-4alkyl-C(O)NRYRz-,
-C0-4alkyl-NRYC(O)RZ, -C(O)NRZORY,
-C0-4alkyl-NRYCO2RY,
-C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY,
-C0-4alkyl-NRWSO2RY,
1,3-dehydrobenzperidol-2-on-1-Il,
1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-Il,
-C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY,
-C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen,,and;
ii) a 5-7 membered heterocyclic ring HetRchaving one additional heteroatom separated from the specified attached nitrogen at least one carbon atom, where the specified additional heteroatom selected from the group consisting of O, S(=O)2and >NRMwhere specified 5-7-membered heterocyclic is some ring HetR cis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RYand RZ;
iii) one of the 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as-C0-4alkyl-RZ- 0-4alkyl-CO2RY;
iv) one of the benzimidazole-1-Il,
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl}piperidine-1-Il,
4-{[(2-aminocyclohexanol)amino]methyl}piperidine-1-Il,
9-Il-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
4-oxo-1-phenyl-1,3,8-diazaspiro[4.5]Dec-8-yl, and
where the Deputy HetRarepresents a 6-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas heteroatom, where said heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;
RKselected from the group consisting of H and-C1-4of alkyl;
RLselected from the group consisting of-CO2RS;
RSrepresents hydrogen;
RMselected from the group consisting of RZ, -C(O)RY;
RNselected from the group consisting of co3, Cl, F, Br, I, HE, NH2CN, CF3CH3and NO2;
RQselected from the group consisting of-CN, -C0-4alkyl-ORY- 0-4alkyl-CO2RY- 0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY;
RWselected from the group consisting of RY;
RXselected from the group consisting of-ORY, -NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;
RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1 or 2 substituents RN;
RZselected from the group consisting of RY- 1-2alkyl-CO2RY;
RArrepresents a radical having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, pyridyl and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0.1 or 2 RNor 0 1 or RL;
RAr'is a 5-6-membered ring which has 1 or 2 heteroatoms selected from the group consisting of O, S, N and NRYand has 0 or 2 bonds and 0 or 1 carbonyl group, where each member with a valid valence in each of the indicated the data of the rings is independently substituted by 0 or 1 or 2 R K;
provided that:
(a) at least one of the R2'and R3'is not ethyl when one of the combinations (s1), (s2), (s3) and (s4), where each of these combinations is defined as follows:
(s1): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents S;
(s2): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents NH;
(s3): R4represents N, Z represents O, W represents CH2, Y is Oh, and X represents S;
(s4): R4represents 5-chloro, Z represents O, W represents CH2, Y is CH2and X represents S;
(b) further provided that when Z is a bond, Y is CH2W represents CHR1-CH2, R1represents H and one of R2'and R3'represents 1H-imidazol-2-yl, any of the R2'and R3'selected from A1), B)-L), where (B)-(L) defined above for the compounds of formula (II), and A1) consists of H, C3-7alkenyl, where the carbon atom at the specified3-7alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom is in the specified quinil, which is connected to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl, and
(C) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2'and R3'is not XCG, if the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl,
halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO.

13. The method according to item 12, where the specified R4represents N.

14. The method according to item 12, where these R2'and R3'each independently selected from the group consisting of A), B), (C) and (I) as defined in item 12.

15. The method according to item 12, where these R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii), as defined in item 12.

16. The method according to item 12, where the specified LTA4H-mediated condition is an inflammation associated with at least one disease, such as asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

17. The method according to clause 16, where at least one specified LTA4H modulator selected from compounds of the formula (III)

or their enantiomers, racemate or pharmaceutically acceptable salts, where
X is selected from the group consisting of NR5, O and S, where R5represents one of N and CH3;
Y represents O;
Z is selected from the group consisting of O and communication;
W is selected from the group consisting of CH2and CHR1-CH2where R1represents H or HE, and where associated with R1carbon group in the specified CHR1-CH2not directly linked to the nitrogen atom is linked to the specified W;
R4selected from the group consisting of H, och3and Cl;
R6represents H or F; and
R2"and R3"each independently selected from the group consisting of:
A) H, C1-7of alkyl, C3-7cycloalkyl,3-7cycloalkyl-C1-7of alkyl, where each of the substituents (a) are independently substituted by 0 or 1 RQ, where each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;
B) Deputy HetRa;
C) -C1-7alkyl-C(O)Rx;
N) -C0-4alkyl-Ar5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group >NRYand 0 or 1 additional heteroatom-N=, and optionally contains two carbonyl groups, and optionally benzododecinium;
I) -C0-4alkyl-Ar5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom;
M) SO2C1-4of alkyl;
alternative, R2"and R3"taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the attached nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of
i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY-CN, -C(O)RY- 0-4alkyl-CO 2RY,
-C0-4alkyl-C(O)CO2RY- 0-4alkyl-ORY- 0-4alkyl-C(O)NRYRz-,
-C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY,
-C0-4alkyl-NRYCO2RY,
-C0-4alkyl-NRYC(O)NRYRY- 0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY,
-C0-4alkyl-NRWSO2RY,
1,3-dehydrobenzperidol-2-on-1-Il,
1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-Il,
-C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY,
-C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen,,and;
ii) a 5-7 membered heterocyclic ring HetRchaving one additional heteroatom separated from the specified attached nitrogen at least one carbon atom, where the specified additional heteroatom selected from the group consisting of O, S(=O)2and >NRMwhere specified 5-7-membered heterocyclic ring HetRCis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RYand RZ ;
hi one of the 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as-C0-4alkyl-RZ- 0-4alkyl-CO2RY;
iv) one of the benzimidazole-1-Il,
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl}piperidine-1-Il,
4-{[(2-aminocyclohexanol)amino]methyl} piperidine-1-Il,
9-Il-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
4-oxo-1-phenyl-1,3,8-diazaspiro[4.5]Dec-8-yl, and
where the Deputy HetRarepresents a 6-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas heteroatom, where said heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;
RKselected from the group consisting of H and-C1-4of alkyl;
RLselected from the group consisting of-CO2RS;
RSrepresents hydrogen;
RMselected from the group consisting of RZ, -C(O)CRY;
RNselected from the group consisting of co3, Cl, F, Br, I, HE, NH2CN, CF3CH3and NO2;
RQselected from the group consisting of-CN, -C0-4alkyl-ORY- 0-4alkyl-CO2RY- 0-4alkyl-NRYRY- 0-4alkyl-N YCORY-C0-4alkyl-NRYCONRYRZ,
-C0-4alkyl-NRYSO2RY;
RWselected from the group consisting of RY;
RXselected from the group consisting of-ORY, -NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;
RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1 or 2 substituents RN;
RZselected from the group consisting of RY, -C1-2alkyl-CO2RY;
RArrepresents a radical having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, pyridyl and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0.1 or 2 RNor 0 1 or RL;
RAr'is a 5-6-membered ring which has 1 or 2 heteroatoms selected from the group consisting of O, S, N and >NRYand has 0 or 2 bonds and 0 or 1 carbonyl group, where each member with a valid valence in each of these rings is independently substituted by 0 or 1 or 2 RK;
provided that:
(a) the R2"and R3", further satisfy one of the following conditions:
(E1): at least one of the specified R 2"
and R3"isn't C1-5the alkyl when Z represents O, and X represents S;
(E2): none of the R2"and R3"is not-C1-4alkyl-C(O)RXwhere RXrepresents one of the1-4of alkyl, HE, -OS1-4of alkyl, -OS0-4alkyl-RAror-NRYRYif Y is O, Z is a bond, and R2"differs from R3";
(E3) none of R2"and R3"is not-C1-4alkyl-CN, if Y is O, Z is a bond, and R2"differs from R3";
(b) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2"and R3"is not XCG, if the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl,
halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO.

18. The method according to 17, where these R2"and R3"each independently selected from the group consisting of A), B), (C) and (I), as defined in 17.

19. SP who own at 17, where indicated R2"and R3"taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii), as defined in 17.

20. The method according to 17, where the specified LTA4H-mediated condition is an inflammation associated with at least one disease, such as asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

21. Method of inhibiting NTAN-enzymatic activity capable of handling the LTA4H enzyme inhibiting amount of at least one LTA4H modulator selected from compounds of the formula (II)

or their enantiomers, racemate or pharmaceutically acceptable salts,
where R2', R3', R4, R6X, Y, Z and W are as defined for compounds of formula (II) according to claim 1, provided that:
(a) at least one of the R2'and R3'is not ethyl when one of the combinations (s1), (s2), (s3) and (s4), where each of these combinations is defined as follows:
(s1): R4represents N, Z n is ecstasy themselves About, W represents CH2, Y is CH3and X represents S;
(s2): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents NH;
(s3): R4represents N, Z represents O, W represents CH2, Y is Oh, and X represents S;
(s4): R4represents 5-chloro, Z represents O, W represents CH2, Y is CH2and X represents S; and
(b) further provided that when Z is a bond, Y is CH2W represents CHR1-CH2, R1represents H and one of R2'and R3'represents 1H-imidazol-2-yl, any of the R2'and R3'selected from A1), B)-L), where (B)-(L) defined above for the compounds of formula (II), and A1) consists of H, C3-7alkenyl, where the carbon atom at the specified3-7alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom in the specified quinil, which is linked to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl, and
(C) further, if X is predstavljaet a S Y is O, Z is a bond, and W represents CH2then one of R2'and R3'is not XCG, if the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl,
halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup (>N-C(O)-) with the nitrogen atom to which is attached the GO.

22. The method according to item 21, where the specified R4represents N.

23. The method according to item 21, where these R2'and R3'each independently selected from the group consisting of A), B), (C) and (I), as defined in item 21.

24. The method according to item 21, where these R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii), as defined in item 21.

25. The method according to item 21, where the specified LTA4H-mediated condition is an inflammation associated with at least one disease, such as asthma, chronic obstructive pulmonary disease, atherosclerosis, repmat idny arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

26. Pharmaceutical composition having the property of inhibitor leukotriene A4-hydrolases (LTA4H), containing a therapeutically effective amount of at least one of the compounds of the formula (II)

or their enantiomers, racemate or pharmaceutically acceptable salts,
where R2', R3', R4, R6X, Y, Z and W are as defined for compounds of formula (II) according to claim 1, provided that:
(a) at least one of the R2'and R3'is not ethyl when one of the combinations (s1), (s2), (s3) and (s4), where each of these combinations is defined as follows:
(s1): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents S;
(s2): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents NH;
(s3): R4represents N, Z represents O, W represents CH2, Y is Oh, and X represents S;
(s4): R4represents 5-chloro, Z represents O, W represents CH2, Y is CH2and X represents S;
(b) next, if the EU is and Z is a bond, Y represents CH2W represents CHR1-CH2, R1represents H and one of R2'and R3'represents 1H-imidazol-2-yl, any of the R2'and R3'selected from A1), B)-L), where (B)-(L) defined above for the compounds of formula (II), and Al) consists of H, C3-7alkenyl, where the carbon atom at the specified3-7alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom in the specified quinil, which is linked to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl, and
(c) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2'and R3'is not XCG, if the other represents C1-6alkyl, where XCG is a group

where HC16 represents one of H, C1-6of alkyl, halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy=O, forming aminogroup with the nitrogen atom to which is attached the group GO, and
pharmaceutically acceptable Eitel, the filler or diluent.

27. The pharmaceutical composition according p where the specified R4represents N.

28. The pharmaceutical composition according p, where these R2'and R3'each independently selected from the group consisting of A), B), (C) and (I), as defined in p.

29. The pharmaceutical composition according p, where these R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii)as defined in p.

30. The pharmaceutical composition according p, where the specified compound of formula (II)
is at least one of the following connections:
2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzooxazol;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dibutylamine;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol;
2-[4-(2-piperidine-1-retil)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}College militiamen;
1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}piperidine-4-ol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]-2-hydroxypropyl}-4-phenylpiperidine-4-ol;
ethyl ester of 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl} dimethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dimethylamine;
2-[4-(2-azepin-1 ylethoxy)phenoxy]benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
2-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-carbonitrile;
1-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)Etalon;
2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}butylethylamine;
2-{4-[2-(4-benzylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol;
2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}propylamino)ethanol;
2-[4-(2-azetidin-1 ylethoxy)phenoxy] benzooxazol;
N-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
ethyl ester of 1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
2-{4-[3-(4-phenylpiperazin-1-yl)propoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
2-[4-(2-pyrrolidin-1-retil)phenoxy]benzooxazol;
2-[4-(2-azepin-1-retil)phenoxy]benzooxazol;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}dibutylamine;
1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
methyl ester 1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}-4-phenylpiperidine-4-ol;
2-[4-(3-pyrrolidin-1-ylpropyl)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}dibutylamine;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclopropanemethylamine;
1-[4-(benzooxazol-2-yloxy)phenoxy]-3-pyrrolidin-1-improper-2-ol;
1-[2-(4-benzooxazol-2-ylmethylene)ethyl]-4-phenylpiperidine is n-4-ol;
amide 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2-[4-(2-morpholine-4-ylethoxy)phenoxy)benzooxazol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}diethylamine;
{2-[4-(6-chlorobenzothiazole-2-yloxy)phenoxy]ethyl}diethylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-1-ylmethanone;
ethyl ester of 3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he;
8-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2,8-diazaspiro[4.5]Decan-1-he;
2-[4-(3-pyrrolidin-1 ipropose)phenoxy)benzothiazole;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-methyl-1,3-dehydrobenzperidol-2-he;
methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(bentot the azole-2-yloxy)phenyl]ethyl}piperidine-4-yl)-(4-methylpiperazin-1-yl)methanon;
methyl ether of 1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamino)propionic acid;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dimethylamine;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzothiazole;
{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}dimethylamine;
2-[4-(2-azepin-1 ylethoxy)phenoxy]benzothiazole;
2-[4-(2-azepin-1 ylethoxy)phenoxy]-6-methoxybenzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dibutylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipiperidine;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethoxy}-phenoxy)benzothiazole;
2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethyl}phenoxy)benzothiazole;
1-{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
1-{2-[4-(b shall societal-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
2-[4-(2-pyrrolidin-1-retil)phenoxy]benzothiazole;
2-[4-(2-azepin-1-retil)phenoxy]benzothiazole;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}dibutylamine;
2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl }piperidine-4-yl)acetic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dihydroindol-2-he;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)pyrrolidin-2-he;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-2-phenylacetamide;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-2,8-diazaspiro[4.5]Decan-1-he;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-ol;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1'-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-[1,4']bipiperidine;
2-{4-[2-(4-methylpiperazin-1-yl)ethyl]phenoxy}benzothiazole;
2-(4-{2-[4-(1-benzyl-1H-tetrazol-5-yl)piperidine-1-yl]ethoxy}phenoxy)benzothiazole;
tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-ilok and)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-carboxylic acid;
amide 1-[2-(4-{benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
1-{1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-yl}pyrrolidin-2-he;
1-[4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-yl]Etalon;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-tion;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)ethanol;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-2-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)acetic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl }piperidine-4-yl)carbamino acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)methanol;
methyl ether ({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylamino)acetic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-1-yl)acetic acid
ethyl ester of 1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-chloro-N-cyclopropanesulfonyl;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}isopropylamino)propionic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ylamine;
3-[{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-(1-methylpiperidin-4-yl)amino]propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}benzoylamino)propionic acid;
3-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}amino)propionic acid;
tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)piperidine-1-carboxylic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionic acid;
3-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)propionic acid;
3-[{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}(1 methylpiperidin-4-yl)amino]propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propionic acid;
3-({2-[4 - (benzothiazol-2-yloxy)phenyl]ethyl}-isopropylamino)propionic acid;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1-(1-[2-(4-benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dehydrobenzperidol-2-he;
2-(4-{2-[4-(6-methylpyridin-2-yl]piperazine-1-yl]ethyl}phenoxy)benzothiazole;
2-{4-[2-(4-acanaloniidae-1-yl]ethyl]phenoxy}benzothiazole;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopentylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclobutylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}benzoylamino)propionic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-(4-hydroxyethylpiperazine-1-yl)methanon;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperazine-1-yl]metano;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperidine-1-yl]metano;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)ethanol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-1-ol;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
3-[(1-2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyronitrile;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)propionic acid;
[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
3-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
2-(4-{2-[4-(4-methoxyphenyl)piperazine-1-yl]ethoxy}phenoxy)benzothiazole;
2-{4-[2-(5-piperidine-4-intersol-1-yl)ethoxy]phenoxy}benzothiazole;
(S)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl;
ethyl ester of 2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarboxylic acid;
ethyl ester of 4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-carbonyl)benzoic acid;
2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarbonyl acid;
1-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-2-ol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-1,1,1-tryptophan-2-ol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionamide;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propane-1,2-diol;
2-{4-[2-(5-phenyltetrazol-2-yl)ethoxy]phenoxy}benzothiazole;
2-{4-[2-(5-phenyltetrazol-1-yl)ethoxy]phenoxy}benzothiazole;
N-{2-[4-(benzodiaz the l-2-yloxy)phenyl]ethyl}-N-cyclopropyl-2-(2H-tetrazol-5-yl)ndimethylacetamide;
(S)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
(R)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
2-{4-[2-(5-methylsulfonylmethyl-2-yl)ethoxy]phenoxy}benzothiazole;
2-{4-[2-(5-methylsulfonylmethyl-1-yl)ethoxy]phenoxy}benzothiazole;
2-[4-(2-tetrazol-2-ylethoxy)phenoxy]benzothiazole;
2-[4-(2-tetrazol-1 ylethoxy)phenoxy]benzothiazole;
(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)butyric acid;
(R)-1-(l-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
hydrochloride of 2-{4-[2-(5-piperidine-4-intersol-2-yl)ethoxy]phenoxy}benzothiazole;
7-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]-4-Spiro[3-phtalic]piperidine;
ethyl ester of 1-{3[4-(benzothiazol-2-yloxy)phenyl]propyl}piperidine-4-carboxylic acid;
hydrochloride of 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine;
2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethoxy]phenoxy)benzothiazole;
triftoratsetata salt of CIS-4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino }cyclohexanecarboxylic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amide propane-2-sulfonic acid;
methyl ester of (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid;
triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)benzosulfimide;
triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)methanesulfonamide;
triftoratsetata salt (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)morpholine-4-ylmethanone;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-thiophene-2-ylatason;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-3-ylmethanone;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)cyclopropylmethanol;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-methoxyethanol;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2,2,2-triptoreline;
4-(4-{2-[4-(benzodiaz the l-2-yloxy)phenyl]ethyl}piperazine-1-carbonyl)benzoic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-4-ylmethanone;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(5-methylpyrazine-2-yl)methanon;
(R)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(S)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-3-yl)methanon;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-hydroxyethane;
2-[2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-oxoethyl]Cyclopentanone;
triftoratsetata salt of 3-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)propionic acid;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)oxazolidin-2-he;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)morpholine-3-one;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)morpholine-3-one;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)oxazolidin-2-he;
benzylacetone 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
hydroxyamide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(S)-1-(1-{2-[4-(benzo is eazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbamate acid;
2-{4-[2-(4-foreperiod-1-yl)ethyl]phenoxy}benzothiazole;
2-{4-[2-(4,4-deformability-1-yl)ethyl]phenoxy}benzothiazole;
(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}pyrrolidin-3-ol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)formamide;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)urea;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-phenylazomethine;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylisoleucine;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methanesulfonamide;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylguanine;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1-phenyl-1,3,8-diazaspiro[4.5]Decan-4-one;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-diazaspiro[4.5]decane-2,4-dione;
tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamate acid;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylacetamide;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylmethanesulfonamide;
methyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamoyl]acetic acid;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-ndimethylacetamide;
(1-{2-[4-(benzothiazol-2-ylox is)phenyl]ethyl}piperidine-4-ylcarbonyl)methyl ester acetic acid;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)-3-(1H-imidazol-2-yl)propionic acid;
2-(4-{2-[4-(3-nitropyridine-2-yl)-[1,4]diazepan-1-yl]ethyl}phenoxy)benzothiazole;
ethyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
ethyl ester of 1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
triftoratsetata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethanol;
2-[2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethoxy]ethanol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propan-1-ol;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl(3-tetrazol-1-ylpropyl)amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl(3-pyrrol-1-ylpropyl)amine;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile (2-cyanoethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(2H-tetrazol-5-yl)propyl]amine;
3-[5-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-and the)tetrazol-1-yl]propionitrile;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl[3-(2H-tetrazol-5-yl)propyl]amine;
(2-hydroxy-1,1-dimethylethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(1H-[1,2,4]triazole-5-yl)propyl]amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-methyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-phenyl-1H-[1,2,4]triazole-
3-yl)propyl] amine;
2-(4-{2-[4-(1-methyl-1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
2-(4-{2-[4-(2-methyl-2H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile;
2-(4-{2-[4-(1H-[1,2,3]triazole-4-yl]ethyl}phenoxy)benzothiazole;
ethyl ester of 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}butyric acid;
ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
2-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
1-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-he;
N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylmethyl-1,3-diamine;
methyl ester 5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentanol acid; N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide morpholine-4-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methylsulfonate;
5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentane acid;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}isopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}propylamino)propyl]pyrrolidin-2-he;
ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methanesulfonamide)butyric acid;
({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)acetic acid;
ethyl ester of 6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
ethyl ester of 7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
7-({2-[4-(b shall societal-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl] isobutyramide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]benzamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-4-chlorobenzamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide;
triftoratsetata salt [3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide propane-2-sulfonic acid;
ethyl ester 8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-3-phenylacetone;
8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide tetrahydrofuran-2-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-2-hydroxyacetate;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
2-[4-(2-morpholine-4-ylethoxy)phenoxy]benzothiazole;
2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzothiazole;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(1H-benzo idazole-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
cyclohexylethyl {2-[4-(1-methyl-1H-benzoimidazol-2-yloxy)phenyl]ethyl}amine;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
2-[4-(2-pyrrolidin-1-retil)phenoxy]-1H-benzoimidazol;
2-[4-(2-azepin-1-retil)phenoxy]-1H-benzoimidazol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}dibutylamine;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
methyl ester 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}cyclohexylamine;
2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-[2-(4-piperidine-1-ylethoxy)phenoxy]-1H-benzoimidazol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
1-[4-(2-azepin-1 ylethoxy)phenoxy]-1H-benzoimidazole;
{3-[4-(1H-benzoimidazol-2-yloxy)phenoxy]propyl]dimethylamine;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]-1H-benzoimidazol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl]dimethylamine;
2-[4-(2-morpholine-4-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1-(1-{2-[4-(1H-benzoni the azole-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol and ethyl ester of 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl} piperidine-4-carboxylic acid.

31. The pharmaceutical composition according p, where the specified compound of formula (II) is at least one of the compounds (III)

or their enantiomers, racemate or pharmaceutically acceptable salts, where
R2", R3", R4, R6X, Y, Z and W are as defined for compounds of formula (III) according to claim 2, provided that:
(a) the R2"and R3", further satisfy one of the following conditions:
(E1): at least one of the R2"and R3"isn't C1-5the alkyl when Z represents O, and X represents S;
(E2): none of the R2"and R3"is not-C1-4alkyl-C(O)RXwhere RXrepresents one of the1-4of alkyl, HE, -OS1-4of alkyl, -OS0-4alkyl-RAror-NRYRYif Y is O, Z is a bond, and R2"differs from R3";
(E3) none of R2"and R3"is not-C1-4alkyl-CN, if Y is O, Z is a bond, and R2"differs from R3";
(b) further provided that when X represents S, Y represents O, Z is the Wallpaper link, and W represents CH2then one of R2"and R3"is not XCG, if the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl, halogen-C1-6of alkyl, allyl and
C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO,

32. The pharmaceutical composition according p where the specified R4represents N.

33. The pharmaceutical composition according p, where these R2"and R3"each independently selected from the group consisting of A), B), (C) and (I), as defined in p.

34. The pharmaceutical composition according p, where these R2"and R3"taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii)as defined in p.

35. The compound of formula (II)

and its enantiomer, racemate or pharmaceutically acceptable salt, where
X is selected from the group consisting of NR5, O and S, where R5depict is to place one of N and CH 3;
Y represents O;
Z is selected from the group consisting of O and communication;
W is selected from the group consisting of CH2and CHR1-CH2where R1represents H or HE, and where associated with R1carbon group in the specified CHR1-CH2not directly linked to the nitrogen atom is linked to the specified W;
R4selected from the group consisting of H, och3and Cl;
R6represents H or F; and
R2'and R3'each independently selected from the group consisting of:
A) H, C1-7of alkyl, C3-7cycloalkyl,3-7cycloalkyl-C1-7of alkyl, where each of the substituents (a) are independently substituted by 0 or 1 RQwhere each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;
B) Deputy HetRa;
C) -C1-7alkyl-C(O)Rx;
N) -C0-4alkyl-Ar5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group >NRYand 0 or 1 additional heteroatom-N=, and optionally contains two carbonyl groups, and optionally benzododecinium;
I) -C0-4alkyl-Ar5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom;
M) SO2C1-4of alkyl;
viola is native, R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the attached nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of
i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY, -CN, -C(O)RY- 0-4alkyl-CO2RY,
-C0-4alkyl-C(O)CO2RY- 0-4alkyl-ORY- 0-4alkyl-C(O)NRYRz-,
-C0-4alkyl-NRYC(O)RZ-, -C(O)NRZRY,
-C0-4alkyl-NRYCO2RY,
-C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY,
-C0-4alkyl-NRWSO2RY,
1,3-dehydrobenzperidol-2-on-1-Il,
1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol-5-Il,
-C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY,
-C0-4alkyl-N(RY)(SO2)NRYCO2RY , halogen,,and;
ii) a 5-7 membered heterocyclic ring HetRchaving one additional heteroatom separated from the specified attached nitrogen at least one carbon atom, where the specified additional heteroatom selected from the group consisting of O, S(=O)2and >NRMwhere specified 5-7-membered heterocyclic ring HetRcis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RYand RZ;
iii) one of the 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as-C0-4alkyl-RZ- 0-4alkyl-CO2RY;
iv) one of the benzimidazole-1-Il,
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl}piperidine-1-Il,
4-{[(2-aminocyclohexanol)amino] methyl} piperidine-1-Il,
9-Il-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
4-oxo-1-phenyl-1,3,8-diazaspiro[4.5]Dec-8-yl, and
where the Deputy HetRarepresents a 6-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas the heteroatoms, where the heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;
RKselected from the group consisting of H and-C1-4of alkyl;
RLselected from the group consisting of-CO2RS;
RSrepresents hydrogen;
RMselected from the group consisting of RZ, -C(O)RY;
RNselected from the group consisting of co3, Cl, F, Br, I, HE, NH2CN, CF3CH3and NO2;
RQselected from the group consisting of-CN,
-C0-4alkyl-ORY-C0-4alkyl-CO2RY- 0-4alkyl-NRYRY- 0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ-C0-4alkyl-NRYSO2RY;
RWselected from the group consisting of RY;
RXselected from the group consisting of-ORY-NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;
RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1 or 2 substituents RN;
RZselected from the group consisting of RY- 1-2alkyl-CO2RY;
RArrepresents a radical having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, is iridia and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0.1 or 2 RNor 0 1 or RL;
RAr'is a 5-6-membered ring which has 1 or 2 heteroatoms selected from the group consisting of O, S, N and >NRYand has 0 or 2 bonds and 0 or 1 carbonyl group, where each member with a valid valence in each of these rings is independently substituted by 0 or 1 or 2 RK;
provided that:
(a) at least one of the R2'and R3'is not ethyl when one of the combinations (s1), (s2), (s3) and (s4), where each of these combinations is defined as follows:
(s1): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents S;
(s2): R4represents N, Z represents O, W represents CH2, Y is CH2and X represents NH;
(s3): R4represents N, Z represents O, W represents CH2, Y is Oh, and X represents S;
(s4): R4represents 5-chloro, Z represents O, W represents CH2, Y is CH2and X represents S;
(b) further provided that when Z represents with the IDE, Y represents CH2W represents CHR1-CH2, R1represents H and one of R2'and R3'represents 1H-imidazol-2-yl, any of the R2'and R3'selected from A1), B)-L), where (B)-(L) defined above for the compounds of formula (II), and A1) consists of H, C3-7alkenyl, where the carbon atom at the specified3-7alkenyl, which is linked to the nitrogen atom has only simple communication; C3-7the quinil, where the carbon atom in the specified quinil, which is linked to the nitrogen atom has only simple communication; C3-7cycloalkyl, optional benzododecinium; C5-7cycloalkenyl; C3-7cycloalkyl-C1-7of alkyl; -C1-7alkyl-C3-7cycloalkyl, and
(c) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2'and R3'is not XCG, if the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl, halogen-C1-6of alkyl, allyl and
C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO.

36. Connection p where asany R 4represents N.

37. Connection p, where these R2'and R3'each independently selected from the group consisting of A), B), (C) and (I), as defined in p.

38. Connection p, where these R2'and R3'taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii)as defined in p.

39. Connection p, where the specified compound of formula (II) is one of the following connections:
2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzooxazol;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl }dibutylamine;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol;
2-[4-(2-piperidine-1-retil)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclohexylethylamine;
1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}piperidine-4-ol;
1-{3-[4-(benzooxazol-2-yloxy)phenoxy]-2-hydroxypropyl}-4-phenylpiperidine-4-ol;
ethyl EF the p 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenoxy]propyl}dimethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}dimethylamine;
2-[4-(2-azepin-1 ylethoxy)phenoxy]benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
2-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-carbonitrile;
1-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)Etalon;
2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}butylethylamine;
2-({2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}benzylamino)ethanol;
2-{4-[2-(4-benzylpiperidine-1-yl)ethoxy]phenoxy}benzooxazol;
(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol;
2-({2-[4-(benzooxazol-2-yloxy)Fenox is]ethyl}propylamino)ethanol;
2-[4-(2-azetidin-1 ylethoxy)phenoxy]benzooxazol;
N-(1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
ethyl ester of 1-{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
2-{4-[3-(4-phenylpiperazin-1-yl)propoxy]phenoxy}benzooxazol;
1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
2-[4-(2-pyrrolidin-1-retil)phenoxy]benzooxazol;
2-[4-(2-azepin-1-retil)phenoxy]benzooxazol;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}dibutylamine;
1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
methyl ester 1-{2-[4-(benzooxazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1-{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}-4-phenylpiperidine-4-ol;
2-[4-(3-pyrrolidin-1-ylpropyl)phenoxy]benzooxazol;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}dibutylamine;
{3-[4-(benzooxazol-2-yloxy)phenyl]propyl}cyclopropanemethylamine;
1-[4-(benzooxazol-2-yloxy)phenoxy]-3-pyrrolidin-1-improper-2-ol;
1-[2-(4-benzooxazol-2-ylmethylene)ethyl]-4-phenylpiperidine-4-ol;
amide 1-[2-(4-benzooxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2-[4-(2-morpholine-4-ylethoxy)phenoxy)benzooxazol;
{2-[4-(benzooxazol-2-yloxy)phenoxy]ethyl}diethylamine; {2-[4-(6-chlorobenzothiazole-2-yloxy)phenoxy]ethyl}diethylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-1-ylmethanone;
ethyl ester of 3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-2-he;
8-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-2,8-diazaspiro[4.5]Decan-1-he;
2-[4-(3-pyrrolidin-1 ipropose)phenoxy)benzothiazole;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-methyl-1,3-dehydrobenzperidol-2-he;
methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-(4-methylpiperazin-1-yl)methanon;
methyl ether of 1-[2-(4-benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
3-({2-[4-(benzothiazol-2-ilok and)phenoxy]ethyl}cyclopropylamino)propionic acid;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dimethylamine;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzothiazole;
{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}dimethylamine;
2-[4-(2-azepin-1 ylethoxy)phenoxy]benzothiazole;
2-[4-(2-azepin-1 ylethoxy)phenoxy]-6-methoxybenzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}dibutylamine;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipiperidine;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethoxy}-phenoxy)benzothiazole;
2-(4-{2-[4-(2-morpholine-4-retil)piperazine-1-yl]ethyl}phenoxy)benzothiazole;
1-{3-[4-(benzothiazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
2-[4-(2-pyrrolidin-1-retil)phenoxy]benzothiazole;
2-[4-(2-azepin-1-retil)phenoxy]benzothiazole;
{2-[4-(benzothiazol-2-ylox is)phenyl]ethyl}cyclopropanemethylamine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}dibutylamine;
2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-carboxylic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dihydroindol-2-he;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)pyrrolidin-2-he;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-2-phenylacetamide;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-2,8-diazaspiro[4.5]Decan-1-he;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-ol;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1'-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-[1,4']bipiperidine;
2-{4-[2-(4-methylpiperazin-1-yl)ethyl]phenoxy}benzothiazole;
2-(4-{2-[4-(1-benzyl-1H-tetrazol-5-yl)piperidine-1-yl]ethoxy}phenoxy)benzothiazole;
tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-carboxylic acid;
amide 1-[2-(4-{benzothiazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
1-{1-[2-(4-besot the azole-2-ylmethylene)ethyl]piperidine-4-yl}pyrrolidin-2-he;
1-[4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)piperazine-1-yl]standard;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-tion;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)ethanol;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-2-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)acetic acid;
ethyl ester of 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)carbamino acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)acetic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-yl)methanol;
methyl ether ({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylamino)acetic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-1-yl)acetic acid;
ethyl ester of 1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl }piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]et the l}piperidine-4-yl)-5-oxopyrrolidin-2-carboxylic acid;
4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-chloro-N-cyclopropanesulfonyl;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}isopropylamino)propionic acid;
1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-ylamine;
3-[{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-(1-methylpiperidin-4-yl)amino]propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}benzoylamino)propionic acid;
3-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl} amino)propionic acid;
tert-butyl ester 4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)piperidine-1-carboxylic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionic acid;
3-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)propionic acid;
3-[{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}(1 methylpiperidin-4-yl)amino]propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-isopropylamino)propionic acid;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-Urbanova acid;
1-(1-[2-(4-benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-1,3-dehydrobenzperidol-2-he;
2-(4-{2-[4-(6-methylpyridin-2-yl]piperazine-1-yl]ethyl}phenoxy)benzothiazole;
2-{4-[2-(4-acanaloniidae-1-yl]ethyl]phenoxy}benzothiazole;
2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-morpholine-4-ylatason;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopentylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclobutylamine)propionic acid;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}benzoylamino)propionic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-(4-hydroxyethylpiperazine-1-yl)methanon;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperazine-1-yl]metano;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-[4-(2-hydroxyethyl)piperidine-1-yl]metano;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)ethanol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-1-ol;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
3-[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amino]propionic acid;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyrone the reel;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)propionic acid;
[(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
3-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-yl)phenol;
2-(4-{2-[4-(4-methoxyphenyl)piperazine-1-yl]ethoxy}phenoxy)benzothiazole;
2-{4-[2-(5-piperidine-4-intersol-1-yl)ethoxy]phenoxy}benzothiazole;
(S)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl;
ethyl ester of 2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]
cyclopropanecarbonyl acid;
ethyl ester of 4-(4-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperazine-1-carbonyl)benzoic acid;
2-[({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)methyl]cyclopropanecarbonyl acid;
1-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propan-2-ol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-1,1,1-tryptophan-2-ol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propionamide;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propane-1,2-diol;
2-{4-[2-(5-phenyltetrazol-2-yl)ethoxy]phenoxy}benzothiazole;
2-{4-[2-(5-phenyltetrazol-1-yl)ethoxy]phenoxy}benzothiazole;
N-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N-cyclopropyl-2-(2H-tetrazol-5-yl)ndimethylacetamide;
(S)-3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
(R)-3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropan-1-ol;
2-{4-[2-(5-methylsulfonylmethyl-2-yl)ethoxy]phenoxy}benzothiazole;
2-{4-[2-(5-methylsulfonylmethyl-1-yl)ethoxy]phenoxy}benzothiazole;
2-[4-(2-tetrazol-2-ylethoxy)phenoxy]benzothiazole;
2-[4-(2-tetrazol-1 ylethoxy)phenoxy]benzothiazole;
(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanecarbonyl acid;
(1R,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
(1S,2R)-2-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}cyclohexanol;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)butyric acid;
(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
ethyl ester of (1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-1H-tetrazol-5-yl)acetic acid;
hydrochloride of 2-{4-[2-(5-piperidine-4-intersol-2-yl)ethoxy]phenoxy}benzothiazole;
7-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl]-4-Spiro[3-phtalic]piperidine;
ethyl ester of 1-{3-[4-(benzothiazol-2-yloxy)phenyl]propyl}piperidine-4-carboxylic acid;
hydrochl the reed 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine;
2-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethoxy]phenoxy)benzothiazole;
triftoratsetata salt of CIS-4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino }cyclohexanecarboxylic acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)amide propane-2-sulfonic acid;
methyl ester of (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid;
triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)benzosulfimide;
triftoratsetata salt of N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonyl)methanesulfonamide;
triftoratsetata salt (4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)octoxynol acid;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)morpholine-4-ylmethanone;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-thiophene-2-ylatason;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-3-ylmethanone;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)cyclopropylmethanol;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-methoxyethanol;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2,2,2-triptoreline;
4-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-carbonyl)benzoic KIS the PTA;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)pyridine-4-ylmethanone;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(5-methylpyrazine-2-yl)methanon;
(R)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(S)-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-2-yl)methanon;
(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-(tetrahydrofuran-3-yl)methanon;
1-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-hydroxyethane;
2-[2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-2-oxoethyl]Cyclopentanone;
triftoratsetata salt of 3-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)propionic acid;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)oxazolidin-2-he;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)morpholine-3-one;
4-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)morpholine-3-one;
3-(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)oxazolidin-2-he;
benzylacetone 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)acetic acid;
(R)-1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
hydroxyamide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
(S)-1-(1-{2-[4-(benzo is eazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
tert-butyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylcarbamate acid;
2-{4-[2-(4-foreperiod-1-yl)ethyl]phenoxy}benzothiazole;
2-{4-[2-(4,4-deformability-1-yl)ethyl]phenoxy}benzothiazole;
(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}pyrrolidin-3-ol;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)formamide;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)urea;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-phenylazomethine;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylisoleucine;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methanesulfonamide;
1-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-3-cyano-2-methylguanine;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1-phenyl-1,3,8-diazaspiro[4.5]Decan-4-one;
8-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-diazaspiro[4.5]decane-2,4-dione;
tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamate acid;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylacetamide;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-methylmethanesulfonamide;
methyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)methylcarbamoyl] acetic acid;
N-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-N-ndimethylacetamide;
(1-{2-[4-(benzothiazol-2-yloxy)phenyl]those who}piperidine-4-ylcarbonyl)methyl ester acetic acid;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methylamino)-3-(1H-imidazol-2-yl)propionic acid;
2-(4-{2-[4-(3-nitropyridine-2-yl)-[1,4]diazepan-1-yl]ethyl}phenoxy)benzothiazole;
ethyl ester [(1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-carbonyl)methylamino]acetic acid;
ethyl ester of 1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
1'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
triftoratsetata salt of 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid;
2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethanol;
2-[2-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)ethoxy]ethanol;
3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)propan-1-ol;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl(3-tetrazol-1-ylpropyl)amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl(3-pyrrol-1-ylpropyl)amine;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyronitrile (2-cyanoethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(2H-tetrazol-5-yl)propyl] amine;
3-[5-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-and the)tetrazol-1-yl]propionitrile;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropyl[3-(2H-tetrazol-5-yl)propyl]amine;
(2-hydroxy-1,1-dimethylethyl)amide 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(1H-[1,2,4]triazole-5-yl)propyl]amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-methyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylmethyl[3-(5-phenyl-1H-[1,2,4]triazole-3-yl)propyl]amine;
2-(4-{2-[4-(1-methyl-1H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
2-(4-{2-[4-(2-methyl-2H-tetrazol-5-yl)piperidine-1-yl]ethyl}phenoxy)benzothiazole;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile;
2-(4-{2-[4-(1H-[1,2,3]triazole-4-yl]ethyl}phenoxy)benzothiazole;
ethyl ester of 4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}butyric acid;
ethyl ester of 4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
2-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine)butyric acid;
1-(3-{2-[4-(benzothiazol-2-yloxy)phenyl]ethylamino}propyl)pyrrolidin-2-he;
N-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylmethyl-1,3-diamine;
methyl ester 5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentanol acid;
N-[-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide morpholine-4-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methansulfonate;
5-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)pentane acid;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}isopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}propylamino)propyl]pyrrolidin-2-he;
ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
ethyl ester of 4-((1-acetylpiperidine-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}methanesulfonamide)butyric acid;
({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)acetic acid;
ethyl ester of 6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
ethyl ester of 7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid;
7-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)heptane acid;
N-1-{2-[4-(b shall societal-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]isobutyramide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]benzamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-4-chlorobenzamide;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide;
triftoratsetata salt [3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl }cyclopropylamino)propyl]amide propane-2-sulfonic acid;
ethyl ester 8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
1-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-3-phenylacetone;
8-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)octanoic acid;
[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide tetrahydrofuran-2-carboxylic acid;
N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-2-hydroxyacetate;
4-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)butyric acid;
2-[4-(2-morpholine-4-ylethoxy)phenoxy]benzothiazole;
2-[4-(2-piperidine-1-ylethoxy)phenoxy]benzothiazole;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
cyclohexyl is Teal {2-[4-(1-methyl-1H-benzoimidazol-2-yloxy)phenyl]ethyl}amine;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
2-[4-(2-pyrrolidin-1-retil)phenoxy]-1H-benzoimidazol;
2-[4-(2-azepin-1-retil)phenoxy]-1H-benzoimidazol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}dibutylamine;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
methyl ester 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}cyclohexylamine;
2-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-[2-(4-piperidine-1-ylethoxy)phenoxy]-1H-benzoimidazol;
1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
1-[4-(2-azepin-1 ylethoxy)phenoxy]-1H-benzoimidazole;
{3-[4-(1H-benzoimidazol-2-yloxy)phenoxy]propyl]dimethylamine;
2-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]-1H-benzoimidazol;
{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl]dimethylamine;
2-[4-(2-morpholine-4-yl)ethoxy]phenoxy}-1H-benzoimidazol;
2-[4-(2-piperidine-1-retil)phenoxy]benzothiazole;
1-(1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-they
ethyl EF the p 1-{2-[4-(1H-benzoimidazol-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid.

40. The compound of formula (III)

and its enantiomer, racemate or pharmaceutically acceptable salt, where
X is selected from the group consisting of NR5, O and S, where R5represents one of N and CH3;
Y represents O;
Z is selected from the group consisting of O and communication;
W is selected from the group consisting of CH2and CHR1-CH3where R1represents H or HE, and where associated with R1carbon group in the specified CHR1-CH2not directly linked to the nitrogen atom is linked to the specified W;
R4selected from the group consisting of H, och3and Cl;
R6represents H or F; and
R2"and R3"each independently selected from the group consisting of:
A) H, C1-7of alkyl, C3-7cycloalkyl,3-7cycloalkyl-C1-7of alkyl, where each of the substituents (a) are independently substituted by 0 or 1 RQwhere each of these RQDeputy of the carbon atom, which represents at least one carbon atom removed from the nitrogen atom;
B) Deputy HetRa;
C) -C1-7alkyl-C(O)Rx;
N) -C0-4alkyl-Ar5where Ar5represents a 5-membered heteroaryl that has one heteroatom selected from the group >NRYand 0 or 1 additional heteroatom-N=, and not necessarily what will win two carbonyl groups, and optional benzododecinium;
I) -C0-4alkyl-Ar5'where Ar5'represents a 5-membered heteroaryl, which contains 3 or 4 nitrogen atom;
M) SO2C1-4of alkyl;
alternative, R2"and R3"taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the attached nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of
i) a 4-7-membered heterocyclic ring HetRbwhere specified 4-7-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the associated nitrogen atom, and substituted by 0, 1 or 2 identical or different substituents, where these substituents selected from the group consisting of-RY-CN, -C(O)RY- 0-4alkyl-CO2RY,
-C0-4alkyl-C(O)CO2RY- 0-4alkyl-ORY- 0-4alkyl-C(O)NRYRZ-,
-C0-4alkyl-NRYCORZ-, -C(O)NRZRY,
-C0-4alkyl-NRYCO2RY,
-C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRY(CO)CO2RY,
-C0-4alkyl-NRWSO2RY,
1,3-dehydrobenzperidol-2-on-1-Il,
1-RY-1H-tetrazol-5-yl, RY -triazolyl, 2-RY-2H-tetrazol-5-Il,
-C0-4alkyl-C(O)N(RY)(SO2RY),-C0-4alkyl-N(RY)(SO2)NRYRY,
-C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen,,and;
ii) a 5-7 membered heterocyclic ring HetRchaving one additional heteroatom separated from the specified attached nitrogen at least one carbon atom, where the specified additional heteroatom selected from the group consisting of O, S(=O)2and >NRMwhere specified 5-7-membered heterocyclic ring HetRcis 0 or 1 carbonyl group and is substituted by 0, 1 or 2 substituents at the same or different substituted carbon atoms, where these substituents selected from the group consisting of-C(O)RYand RZ;
iii) one of the 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl substituted at the carbon atom 0 or 1 Deputy, such as-C0-4alkyl-RZ- 0-4alkyl-CO2RY;
iv) one of the benzimidazole-1-Il,
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl}piperidine-1-Il,
4-{[(2-aminocyclohexanol)amino]methyl}piperidine-1-Il,
9-Il-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid,
4-oxo-1-FeNi is -1,3,8-diazaspiro[4.5]Dec-8-yl,and
where the Deputy HetRarepresents a 6-membered heterocyclic ring with the carbon atom at the connection point and containing the group >NRMas heteroatom, where said heteroatom is separated from the specified carbon atom in the place of connection of at least 1 carbon atom;
RKselected from the group consisting of H and-C1-4of alkyl;
RLselected from the group consisting of-CO2RS;
RSrepresents hydrogen;
RMselected from the group consisting of RZ-C(O)RY;
RNselected from the group consisting of co3, Cl, F, Br, I, HE, NH2CN, CF3CH3and NO2;
RQselected from the group consisting of-CN, -C0-4alkyl-ORY- 0-4alkyl-NRYRY- 0-4alkyl-NRYCORY- 0-4alkyl-NRYCONRYRZC0-4alkyl-NRYSO2RY,
RWselected from the group consisting of RY;
RXselected from the group consisting of-ORY, -NRYRZ- 1-4the alkyl and-C0-4alkyl-RAr;
RYselected from the group consisting of H, C1-4of alkyl, -C0-4alkyl-RArand-C0-4alkyl-RAr', each of which is substituted by 1 or 2 substituents RN;
RZselected from the group consisting of RY, -C1-2alkyl-CO2RY;
Rsup> Ar
represents a radical having a carbon atom at the position of joining, where the specified radicals selected from the group consisting of phenyl, pyridyl and pyrazinyl, where each carbon atom with a valid valence in each of these groups is independently substituted by at least 0.1 or 2 RNor 0 1 or RL;
RAr'is a 5-6-membered ring which has 1 or 2 heteroatoms selected from the group consisting of O, S, N and >NRYand has 0 or 2 bonds and 0 or 1 carbonyl group, where each member with a valid valence in each of these rings is independently substituted by 0 or 1 or 2 RKand
provided that:
(a) the R2"and R3", further satisfy one of the following conditions:
(E1): at least one of the R2"and R3"isn't C1-5the alkyl when Z represents O, and X represents S;
(E2): none of the R2"and R3"is not-C1-4alkyl-C(O)RXwhere RXrepresents one of the1-4of alkyl, HE, -OS1-4of alkyl, -OS0-4alkyl-RAror-NRYRYif Y is O, Z is a bond, and R2"differs from R3";
(E3) none of R2"and R3"is not-C1-4alkyl-CN, if Y is O, Z is a bond, and R2" differs from R3";
(b) further provided that when X represents S, Y represents O, Z is a bond, and W represents CH2then one of R2"and R3"is not XCG, if the other represents C1-6alkyl, where XCG is a group

where HC16 represents one of H, C1-6of alkyl, halogen-C1-6of alkyl, allyl, and C1-6alkoxymethyl, and GO is a group attached through a carbon atom, which has a Deputy =O, forming aminogroup with the nitrogen atom to which is attached the GO.

41. Connection p where the specified R4represents N.

42. Connection p, where these R2"and R3"each independently selected from the group consisting of A), B), (C) and (I), as defined in p.

43. Connection p, where these R2"and R3"taken together with the nitrogen atom to which they are linked, form a heterocyclic ring containing at least one heteroatom, which is specified by the associated nitrogen atom, where the aforementioned heterocyclic ring selected from the group consisting of (i) and (ii)as defined in p.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to new a compound of formula I or formula II, or to its pharmaceutically acceptable salts, I II, where X is S; R1 is H or C1-C6alkyl; R2 is NR5R6; R3 is aryl, substituted with a halogen; R4 is H; R5 is H; R6 is H; R7 is CH2NR8R9 where R8 is H, C1-C10alkyl, C3-C8cycloalkyl, aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), heterocycle(C1-C6alkyl), heterocycle(C2-C6alkenyl), hydroxyl(C1-C6alkyl), hydroxyl(C2-C6alkyl), C1-C6alkoxycarbonyl, aryl(C1-C6alkoxy)carbonyl, carbamoyl(C1-C6alkyl); where the above mentioned aryl is an aromatic ring and is not substituted or substituted with one to three substituting groups, each of which, independently from the others, is chosen from: methylenedioxy, hydroxy, C1-C6-alkoxy, halogen, C1-C6alkyl, trifluoromethyl, trifluoromethoxy, NO2, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, NH-acyl, N(C1-C6alkyl)-acyl, hydroxy(C1-C6alkyl), dihydroxy(C1-C6alkyl), CN, C(=O)O(C1-C6alkyl), phenyl, phenyl(C1-C6alkyl), phenyl(C1-C6alkenyl), phenoxy and phenyl(C1-C6alkoxy), R9 is H, C1-C10alkyl, heterocycle(C1-C6alkyl) or heterocycle(C2-C6alkenyl); where the above mentioned heterocycle represents a 5-member saturated monocyclic ring system, consisting of carbon atoms, as well as heteroatoms, chosen from a group comprising N, O, and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes NO2, aryl(C1-C6alkyl), arylsulphonyl; or R8 and R9 together with nitrogen, to which they are bonded, form a heterocycle, which represents a 5 - 7-member saturated monocyclic ring system, consisting of carbon atoms, as well as one to three heteroatoms, chosen from a group comprising N, O and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes C1-C6alkoxy, hydroxy, C1-C6alkyl, C2-C6-alkenyl, C(=O)O(C1-C6alkyl), C(=O)NH2, C(=O)NH(C1-C6alkyl), C(=O)N(C1-C6-alkyl)2, hydroxy(C1-C6alkyl), dihydroxy(C2-C6alkyl), aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), aryl(C1-C6alkoxy) and pyrimidin-2-yl; and m equals 0. The invention also relates to a pharmaceutical composition, as well as to use of formula I or formula II compounds.

EFFECT: obtaining new biologically active compounds, with inhibitory properties towards casein kinase 1ε.

32 cl, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds -(Z)-1'-R-6',6'-dimethyl-3-(phenyl(arylamino)methylene)-6',7'-dihydro-3H-spiro[furane-2,3'-indol]-2',4,4',5(1'H,5'H)-tetraons of formula: , where Ar=phenyl, n-methoxyphenyl, n-tollyl; R=allyl, benzyl, phenyl, n-tollyl, n-methoxyphenyl, α-naphtyl, as well as to method of their obtaining, which consists in the following: isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates are subjected to interaction with N-substituted 3-amino-5,5-dimethylcyclohex-2-enons in medium of inert aprotonic solvent with further separation of target products. Process is carried out at temperature 20-22°C. As solvent, absolute chloroform is used.

EFFECT: obtaining compounds possessing analgesic activity.

4 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention is related to compounds of formula (II) as inhibitor of leukotriene A4-hydrolase (LTA4H) and their enantiomers, racemic compounds and pharmaceutically acceptable salts, and also to treatment methods, method inhibition and pharmaceutical composition on their basis. In general formula (II) , X is selected from group that consists of O and S; Y is selected from group that consists of CH2 and O; R4 represents H; R6 represents H or F; and R2' is determined as R2, and R3' is determined as R3, as follows: R2 and R3, each, is independently selected from group that consists of A) H, C1-7alkyl, C3-7cycloalkyl, where each of substitutes of A) is independently substituted with 0 or 1 RQ, and each of mentioned RQ is substitute at carbon, which is distanced from nitrogen at least by one carbon atom; alternatively, R2 and R3, taken together with nitrogen, to which they are connected, create heterocyclic ring, which contains at least one heteroatom, which is specified nitrogen of connection, and specified heterocyclic ring is selected from group that consists of i) (4-7)-member heterocyclic ring HetRb, where specified (4-7)-member heterocyclic ring HetRb has single heteroatom, which is specified nitrogen of connection, and 0, 1 or 2 are substituted by substitutes at the same or different substituted atoms, at that specified substitutes are selected from group that consists of -RY, -C(O)RY, -C0-4alkylCO2RY, -C0-4alkylC(O)NRYRZ, -C0-4alkylNRYC(O)Rz, -C0-4alkylNRYC(O)CH2ORY, -C0-4alkylNRYCO2RY, -C0-4alkylNRYC(O)NRYRz, -C0-4alkylNRyC(S)NRyRz, -NRyC(O)CO2Ry, -C0-4alkylNRwSO2RY, tetrazol-5-yl, -C0-4alkylN(RY)(SO2)NRYRY, -C0-4alkylN(RY)(SO2)NRYCO2RY, ii) (5-7)-member heterocyclic ring HetRc, where specified (5-7)-member heterocyclic ring has single additional heteroatom distanced from specified nitrogen of connection at least by one carbon atom, thereat the specified additional heteroatom is selected from group that consists of O, S(=O)0-2 and >NRM, and where mentioned (5-7)-member heterocyclic ring HetRc has 0 or 1 carbonyl group; iv) one of 2,8-diazaspyro[4.5]decan-1-on-8-yl, 4-{[(2-tret- butoxycarbonylaminocyclobutancarbonyl)amino]methyl}-piperidine-1-yl, 4-{[(2-aminocyclobutancarbonyl)amino]methyl}piperidine-1-yl, tret-butyl ether of 3,9-diazaspyro [5.5]undecan-3-carbonic acid-9-yl; where RK is selected from group that consists of H, -C1-4alkyl, each not necessarily substituted by 1 substitute RN; RM is selected from group that consists of -SO2RY, -C(O)RY, -C(O)C1-4alkylORY, each not necessarily substituted by 1 substitute RN; RN is selected from group that consists of OH, NH2, CF3; RQ is selected from group that consists of -C0-4alkylRAr', -C0-4alkylCO2RY, -C0-4alkylNRYRz, -C0-4alkylNRYCORY, -C0-4alkylNRyCONRyRz; Rw is selected from group that consists of RY and -C3-7cycloalkyl; RY is selected from group that consists of H, -C1-4alkyl, -C0-4alkylRAr and -C0-4alkylRAr', each not necessarily substituted by 1 substitute RN; Rz is selected from group that consists of RY, -C1-2alkylCO2RY; RAr represents fragment connected via carbon atom, and specified fragment is selected from phenyl, pyridyl; RAr' represents (5-6)-member cyclic ring, having 1 or 2 heteroatoms selected from group that consists of O, N and >NRY, having 0 unsaturated connections, having 0 or 1 carbonyl group, where each atom, when allows for valency, in every of mentioned cyclic rings is independently substituted by 0 or 1 RK; provided that (a) specified R2' and R3', moreover, satisfy the following requirements: (e1): specified R2' and R3', both, are not H, when Y represents O and X represents S; (e3): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperazine group, when X represents O and Y is one of O and CH2; (e4): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperidine group, which is mono-substituted by 6-member cyclic group, when X represents O and Y is one of O and CH2; and (e5): specified R2' and R3', taken together with nitrogen, with which they are connected, create neither substituted piperidine group or substituted piperazine group, where specified substituted piperidine group or specified substituted piperazine group is substituted in position 4 by substitute XG, at that specified XG has structure , where n=0, 1, and when ne=1, then XL represents C1-6alkyl, OSG represents O or S, and XR1 and XR2, taken together with nitrogen, with which they are connected, create one of piperidine group, piperazine group, morpholine group, thiomorpholine group and pyrrolidine group, or each of XR1 and XR2, taken independently, represent one of H, C1-6alkyl, aryl, aralkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, heteroalkyl, heteroaryl-C1-6alkyl, heterocycloalkyl and heterocycloalkyl-C1-6alkyl; where aryl, aralkyl, cycloalkyl, heteroaryl or heterocycloalkyl may be not necessarily substituted by one or several substitutes, independently selected from halogen, hydroxy, C1-6alkyl, C1-6alkoxy, halogenated C1-6alkyl, halogenated C1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or heterocycloalkyl; and (b) further provided that when X represents S and Y represents O, then one of R2' and R3' is not XCG, while the other represents C1-6alkyl, where XCG represents group , where HC16 represents one of H, C1-6alkyl, halogenC1-6alkyl, allyl and C1-6alcoxymethyl, and GO represents group connected to carbon atom, which has substitute =0, creating amido group with nitrogen, with which all mentioned GO group is connected.

EFFECT: compounds may find application for treatment and prevention of diseases mediated by LTA4H, for instance, asthma, chronic obstructive lung disease, atherosclerosis, rheumatoid arthritis, disseminated sclerosis, inflammatory disease of bowels and psoriasis.

39 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): their using (variants) for preparing a drug used in treatment of diseases modulation of activity of chemokine receptors is useful, and to a pharmaceutical composition modulating chemokine receptors and comprising abovementioned compound. In compound of the formula (I) m = 0 or 1; R1 means halogen atom; X, Y and Z represent independently a bond, -CH2- or -O-, or X and Y form in common -CH=C(CH3)- or -C(CH3)=CH- under condition that only one radical among X, Y and Z can represents a bond, and under condition that X and Y both don't represent -O- simultaneously; n = 0, 1 or 2; R2 represents halogen atom, or (C1-C6)-alkyl; q = 0 or 1; R3 represents -NHC(O)R10, -C(O)NR11R12 or -COOR12a; each radical among R4, R5, R6, R7 and R8 represents independently hydrogen atom (H) or (C1-C6)-alkyl; t = 0, 1 or 2; R9 represents halogen atom, -OH, -COOH, (C1-C6)-alkoxy group, (C1-C6)-alkoxycarbonyl; R10 represents group (C1-C6)-alkyl, (C3-C6)-cycloalkyl, or R10 represents -NR14R15; each R11 and R12 represents independently (1) H; (2) 3-6-membered saturated cycloalkyl or phenyl or 5-membered unsaturated heterocyclyl comprising from 1 to 4 heteroatoms N wherein indicated cycloalkyl, phenyl and heterocyclyl are substituted possibly with one or two substitutes chosen from -OH, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl; (3) (C1-C6)-alkyl substituted possibly at least with one substitute chosen from halogen atom, -OH, -COOH, (C1-C6)-alkylcarbonylamino group, phenyl, 5-membered unsaturated heterocyclyl comprising oxygen atom (O), or from 1 to 2 N atoms, bicycloheptyl wherein this phenyl, heterocyclyl or bicycloheptyl is substituted possibly at least with one substitute chosen from halogen atom, -OH, =O, or (4) (C1-C6)-alkylsulfonyl, or R11 and R12 in common with N atoms to which they are bound form 5-membered unsaturated heterocyclyl comprising one N atom or 5-6-membered heterocyclyl comprising from 1 to 2 heteroatoms, such as S, O and N, or 5-6-membered saturated heterocyclyl, ortho-condensed with benzene ring and comprising one N atom and wherein indicated heterocyclic systems are substituted possibly with one or two substitutes chosen from halogen atom, (C1-C6)-alkyl, (C1-C6)-hyroxyalkyl, (C1-C6)-halogenalkyl, (C1-C6)-alkylamino, di-(C1-C6)-alkylamino group, phenyl, halogenphenyl and hydroxydiphenylmethyl; R12a represents H or (C1-C6)-alkyl; each radical among R14 and R15 represents independently H or (C1-C6)-alkylsulfonyl, or R14 and R15 in common with N atom to which they are bound form 5-membered saturated heterocyclyl comprising one N atom and substituted possibly with one -OH, or its pharmaceutically acceptable salt or solvate. Also, invention relates to a method (variants) for synthesis of compound of the formula (I) according to one of the following method: by one variant, compound of the formula (II): is subjected for interaction with compound of the formula (III): by other variant, compound of the formula (IV): is subjected for interaction with compound of the formula (V): by other variant, compound of the formula (VI): wherein R3 represents -NHC(O)R10 and L1 represents a leaving group is subjected for interaction with L1C(O)R10; by other variant, compound of the formula (VIII): wherein R3 represents -C(O)NR11R12 and L2 represents a leaving group is subjected for interaction with compound of the formula (IX) given in the invention description. Also, invention relates to an intermediate compound of the formula (IIA): (wherein R1a is chosen from F, Cl, -CH3 and -CF3; s = 1 or 2; q = 0 or 1; w = 0 or 1; R2a represents F, and when q and s = 1 and w = 0 then R1a can't represent chlorine atom), and to a method for synthesis of compound of the formula (IIA) (wherein s = 1) and wherein compound of the formula (XX): is subjected for interaction with compound of the formula (XXII): (wherein R20 represent a protective group) before formation of compound of the formula (XXIV): followed by carrying out the cyclization reaction and removing the protective group R20.

EFFECT: improved methods of synthesis.

25 cl, 236 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compound of the formula (I): wherein (a) each R1 is chosen independently from hydrogen atom and alkoxy-group; (b) R2 represents hydrogen atom; (c) each R3 and R4 is chosen independently of one another from hydrogen atom, alkyl, alkynyl, heteroalkyl group, aryl; or R3 and R4 in common with nitrogen atom bound with them form heteroaryl or heterocycloaryl substitute optionally substituted with one or more hydroxo-group, carboxyl group, keto-, thioketo-, phenyl group, alkyl, heteroalkyl group, heteroaryl, heterocycloalkyl, spirocycloalkyl and their combinations; (d) each R5 and R6 represents hydrogen atom; or optical isomers, diastereomers and enantiomers represented by above given formula, and their pharmaceutically acceptable salts also. Also, invention describes using compound of the formula (I) for preparing a pharmaceutical composition possessing antibacterial activity and antibacterial pharmaceutical composition containing the safety and effective amount of compound of the formula (I) and a pharmaceutically acceptable carrier. Invention provides synthesis of novel compounds possessing useful biological properties.

EFFECT: valuable properties of compounds and pharmaceutical composition.

7 cl, 37 ex

FIELD: organic chemistry, insecticides.

SUBSTANCE: invention relates to compounds of formula I , wherein W is halogen, C1-C6-alkyl, C1-C6-alkoxy, C1-C4-haloalkyl or C1-C4-haloalkoxy; X is hydrogen, halogen, C1-C6-alkyl; Y is hydrogen, halogen, C1-C6-alkyl, C1-C4-haloalkyl, C1-C4-haloalcoxy or cyano; Z is hydrogen, halogen, etc.; G is halogen or nitro; meanings of the other substituents are as defined in specification. Also disclosed are methods for production of said compounds by interaction compounds of formula II with halogenation agents in presence of solvent and optionally of radical initiator of with fumed nitric acid in presence of solvent.

EFFECT: new compounds with insecticide activity.

17 cl, 20 tbl, 114 ex

FIELD: chemistry.

SUBSTANCE: invention is related to compounds of formula (II) as inhibitor of leukotriene A4-hydrolase (LTA4H) and their enantiomers, racemic compounds and pharmaceutically acceptable salts, and also to treatment methods, method inhibition and pharmaceutical composition on their basis. In general formula (II) , X is selected from group that consists of O and S; Y is selected from group that consists of CH2 and O; R4 represents H; R6 represents H or F; and R2' is determined as R2, and R3' is determined as R3, as follows: R2 and R3, each, is independently selected from group that consists of A) H, C1-7alkyl, C3-7cycloalkyl, where each of substitutes of A) is independently substituted with 0 or 1 RQ, and each of mentioned RQ is substitute at carbon, which is distanced from nitrogen at least by one carbon atom; alternatively, R2 and R3, taken together with nitrogen, to which they are connected, create heterocyclic ring, which contains at least one heteroatom, which is specified nitrogen of connection, and specified heterocyclic ring is selected from group that consists of i) (4-7)-member heterocyclic ring HetRb, where specified (4-7)-member heterocyclic ring HetRb has single heteroatom, which is specified nitrogen of connection, and 0, 1 or 2 are substituted by substitutes at the same or different substituted atoms, at that specified substitutes are selected from group that consists of -RY, -C(O)RY, -C0-4alkylCO2RY, -C0-4alkylC(O)NRYRZ, -C0-4alkylNRYC(O)Rz, -C0-4alkylNRYC(O)CH2ORY, -C0-4alkylNRYCO2RY, -C0-4alkylNRYC(O)NRYRz, -C0-4alkylNRyC(S)NRyRz, -NRyC(O)CO2Ry, -C0-4alkylNRwSO2RY, tetrazol-5-yl, -C0-4alkylN(RY)(SO2)NRYRY, -C0-4alkylN(RY)(SO2)NRYCO2RY, ii) (5-7)-member heterocyclic ring HetRc, where specified (5-7)-member heterocyclic ring has single additional heteroatom distanced from specified nitrogen of connection at least by one carbon atom, thereat the specified additional heteroatom is selected from group that consists of O, S(=O)0-2 and >NRM, and where mentioned (5-7)-member heterocyclic ring HetRc has 0 or 1 carbonyl group; iv) one of 2,8-diazaspyro[4.5]decan-1-on-8-yl, 4-{[(2-tret- butoxycarbonylaminocyclobutancarbonyl)amino]methyl}-piperidine-1-yl, 4-{[(2-aminocyclobutancarbonyl)amino]methyl}piperidine-1-yl, tret-butyl ether of 3,9-diazaspyro [5.5]undecan-3-carbonic acid-9-yl; where RK is selected from group that consists of H, -C1-4alkyl, each not necessarily substituted by 1 substitute RN; RM is selected from group that consists of -SO2RY, -C(O)RY, -C(O)C1-4alkylORY, each not necessarily substituted by 1 substitute RN; RN is selected from group that consists of OH, NH2, CF3; RQ is selected from group that consists of -C0-4alkylRAr', -C0-4alkylCO2RY, -C0-4alkylNRYRz, -C0-4alkylNRYCORY, -C0-4alkylNRyCONRyRz; Rw is selected from group that consists of RY and -C3-7cycloalkyl; RY is selected from group that consists of H, -C1-4alkyl, -C0-4alkylRAr and -C0-4alkylRAr', each not necessarily substituted by 1 substitute RN; Rz is selected from group that consists of RY, -C1-2alkylCO2RY; RAr represents fragment connected via carbon atom, and specified fragment is selected from phenyl, pyridyl; RAr' represents (5-6)-member cyclic ring, having 1 or 2 heteroatoms selected from group that consists of O, N and >NRY, having 0 unsaturated connections, having 0 or 1 carbonyl group, where each atom, when allows for valency, in every of mentioned cyclic rings is independently substituted by 0 or 1 RK; provided that (a) specified R2' and R3', moreover, satisfy the following requirements: (e1): specified R2' and R3', both, are not H, when Y represents O and X represents S; (e3): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperazine group, when X represents O and Y is one of O and CH2; (e4): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperidine group, which is mono-substituted by 6-member cyclic group, when X represents O and Y is one of O and CH2; and (e5): specified R2' and R3', taken together with nitrogen, with which they are connected, create neither substituted piperidine group or substituted piperazine group, where specified substituted piperidine group or specified substituted piperazine group is substituted in position 4 by substitute XG, at that specified XG has structure , where n=0, 1, and when ne=1, then XL represents C1-6alkyl, OSG represents O or S, and XR1 and XR2, taken together with nitrogen, with which they are connected, create one of piperidine group, piperazine group, morpholine group, thiomorpholine group and pyrrolidine group, or each of XR1 and XR2, taken independently, represent one of H, C1-6alkyl, aryl, aralkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, heteroalkyl, heteroaryl-C1-6alkyl, heterocycloalkyl and heterocycloalkyl-C1-6alkyl; where aryl, aralkyl, cycloalkyl, heteroaryl or heterocycloalkyl may be not necessarily substituted by one or several substitutes, independently selected from halogen, hydroxy, C1-6alkyl, C1-6alkoxy, halogenated C1-6alkyl, halogenated C1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or heterocycloalkyl; and (b) further provided that when X represents S and Y represents O, then one of R2' and R3' is not XCG, while the other represents C1-6alkyl, where XCG represents group , where HC16 represents one of H, C1-6alkyl, halogenC1-6alkyl, allyl and C1-6alcoxymethyl, and GO represents group connected to carbon atom, which has substitute =0, creating amido group with nitrogen, with which all mentioned GO group is connected.

EFFECT: compounds may find application for treatment and prevention of diseases mediated by LTA4H, for instance, asthma, chronic obstructive lung disease, atherosclerosis, rheumatoid arthritis, disseminated sclerosis, inflammatory disease of bowels and psoriasis.

39 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel derivatives of diazaspiropiperidine of the formula I: , where A-B is -CH2-CH2-, -CH2-O- or -O-CH2-; X is hydrogen or hydroxy; R1 is aryl optionally substituted by one or more substitutes selected out of group including haloid, (lower) alkyl, cyano, CF3, -OCF3, (lower) alkoxy, -SO2-(lower)alkyl, or heteroaryl with two nitrogen atoms; R2 is phenyl optionally substituted by one or more substitutes selected out of group including haloid, (lower) alkyl, CF3 or (lower) alkoxy; R3 is hydrogen or (lower)alkyl; n is 0, 1 or 2; and their pharmaceutically acceptable salts.

EFFECT: medicine based on compounds of the formula 1 and their application in obtaining medicine for neuropathological and neuropsychiatric disease treatment.

12 cl, 1 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (1) where: R1 represents hydrogen atom, halogen, CP3, (1-3C)alkoxy group, m is an integer within 1 to 4, provided when m is equal to 2, 3 or 4, R1 substitutes can be either identical or different, R2 represents hydrogen atom, alkyl (1-6C) group optionally substituted with alkoxy group, cycloalkyl (3-6C) group, -CH2OH, -CH2OCH3, acetyl group, benzyl group optionally substituted with amino group, or group Q of the following composition (2): were: [ ]n symbolically represents -(CH2)n-, where n is an integer within 0 to 7, R3 represents hydrogen atom or alkyl (1-3C) group, R4 represents hydrogen atom, alkyl (1-6C) group optionally substituted with one or more groups, chosen of alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkoxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitr