Derivatives of benzimidazol, benzotiazol and benzoxazol and their application as lta4h modulators

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

 

The scope of the invention

This invention relates to inhibitors hydrolases leukotriene A4 (LTA4H) for the treatment of inflammation. In particular, this invention relates to certain compounds benzoxazol-2-yl, benzothiazol-2-yl and 1H-benzimidazole-2-yl, useful as selective inhibitors of LTA4H enzyme for the treatment of inflammatory conditions.

Prior art

Inflammation is an acute immune system response to the introduction into the organism of microbial pathogens, chemicals, or physical damage. In some cases, however, the inflammatory response may develop into a chronic condition and cause inflammatory diseases. With such chronic inflammation in various diseases therapeutic control becomes medically necessary.

Leukotrienes (LT) are biologically active metabolites of arachidonic acid (B. Samuelsson, Science 1983, 220(4597):568-575), which are involved in inflammatory diseases, including asthma (D.A. Munafo et al., J. Clin. Invest. 1994, 93(3):1042-1050), inflammatory bowel disease (IBD) (Sharon P. and 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. U.S.A. 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 and M.J. Stiller, Skin Pharmaco. Appl. Skin Physiol. 2000, 13(5):235-245) and atherosclerosis (Friedrich, E.B. et al. Arterioscler Thromb Vasc Biol 23, 1761-7 (2003); Subbarao, K. et al. Arterioscler Thromb Vasc Biol 24, 369-75 (2004); Helgadottir, A. 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 (LTA4), via the 5-lipoxygenase (5-LO) (A.W. Ford-Hutchinson et al., Annu. Rev. Biochem. 1994, 63:383-347). This enzyme is expressed predominantly by cells of myeloid origin, especially neutrophils, eosinophils, monocytes/macrophages and mast cells (G.K. Reid et al., J. Biol. Chem. 1990, 265(32):19818-19823). LTA4 can either konjugierte with by glutathione synthase leukotriene C4 (LTC4) obtaining containerisation, LTC4, or either hydrolyzed in diol, leukotriene B4 (LTB4) (B. Samuelsson, Science 1983, 220(4597):568-575). LTC4 and its metabolites LTD4 and LTE4, induce contraction of smooth muscles, bronchostenosis and vascular permeability, whereas LTB4 is a potent chemoattractant and activator of neutrophils.

Stereospecific hydrolysis of LTA4 to LTB4 is catalyzed by hydrolases leukotriene A4 (LTA4H), zinc-containing cytosolic enzyme. This enzyme is widely expressed with high levels in the epithelial cells of the small intestine, lung and aorta. (B. Samuelsson and C.D. Funk, J. Biol. Chem. 1989, 264(33):19469-19472). Moderate expression observed in leukocytes, the particular neutrophils (T. Yokomizo et al., J. Lipid Mediators Cell Signalling 1995, 12(2,3):321-332).

Leukotriene B4 is a key proinflammatory mediator, able to recruit inflammatory cells such as neutrophils and eosinophils, and activated neutrophils (F.A. Fitzpatrick et al., Ann. N.Y. Acad. Sci. 1994, 714:64-74; S.W. Crooks and R.A. Stockley, Int. J. Biochem. Cell Biol. 1998, 30(2):173-178; A. Klein et al., J. Immunol. 2000, 164:4271-4276). LTB4 mediates its Pro-inflammatory actions by binding to receptors associated with G-protein receptor 1 leukotriene B4 (BLT1) and receptor 2 leukotriene B4 (BLT2) (T. Yokomizo et al., Arch. Biochem. Biophys. 2001, 385(2):231-241). The receptor is specified first, BLT1, LTB4 binds with high affinity, leading to intracellular signaling and chemotaxis. BLT1 is expressed mainly in peripheral leukocytes, in particular neutrophils, eosinophils, macrophages (Huang, W.W. 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, as was recently shown, mediates LTB4-dependent 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); 0tt, V.L, Cambier, J.C., Kappler, J., Marrack, P. & Swanson, B.J. Nat Immunol 4, 974-81 (2003)), chemotaxis and adhesion to endothelial cells differentiated effector CD4+T-helper type 1 (TH1) and TH2, and recruitment undifferentiated effect the different CD4 +and CD8+T-cells in animal model of asthma (Tager, A.M. et al., Nat Immunol 4, 982-90 (2003)). Receptor BLT2 leukotriene B4 (LTB4) (S. Wang et al., J. Biol. Chem. 2000, 275(52):40686-40694; T. Yokomizo et al., J. Exp. Med. 2000, 192(3):421-431) shares 42% amino acid homology with BLT1, but it is expressed more widely, including such peripheral tissues, such as tissues of the spleen, ovary and liver, as well as in leukocytes. BLT2 LTB4 binds with a lower affinity than does BLT1, mediates chemotaxis at higher concentrations of LTB4 and differs from BLT1 their affinity for certain antagonists. Although LTB4 receptor antagonists may vary according to the degree of their affinity to the receptor BLT1 in comparison with BLT2, it can be assumed that blocking the production of LTB4, using inhibitors of LTA4H, will lead to inhibition of the events in the course of the processes mediated by both receptor, both BLT1 and BLT2.

Studies have shown that the introduction of exogenous LTB4 in normal cells 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 of LTB4 was observed in several inflammatory diseases, including IBD, COPD, psoriasis, rheumatoid arthritis (RA), cystic fibrosis and asthma (S.W. Crooks and R.A. Stockley, Int. J. Biochem. Cell Biol. 1998, 30(2): 173-178). Therefore, we can predict that the decline in the production of LTB4 by using an inhibitor of the activity of LTA4H Boo is et to have therapeutic potential for a wide range of diseases.

This idea is supported by research conducted on mice with deficiency of LTA4H, healthy in other respects, which showed a marked reduction in the influx of neutrophils in a model of induced arachidonic acid inflammation of the ear and model of the induced simhasanam peritonitis (RS Byrum et al., J. Immunol. 1999, 163(12):6810-6819). In preclinical studies it has been shown that the LTA4H inhibitors are effective anti-inflammatory drugs. For example, oral administration of LTA4H inhibitor, SC57461 caused braking ionophor-induced LTB4 production in murine blood ex vivo and in the peritoneum of rats in vivo (J.K. Kachur et al., J. Pharm. Exp. Ther. 2002, 300(2), 583-587). Eight weeks of treatment with the same connection-inhibitor significantly improved the symptoms of colitis has Zagainov (T.D. Penning, Curr. Pharm. Des. 2001, 7(3):163-179). Spontaneous colitis that develops in these animals is very similar to IBD in humans. Therefore, the obtained results allow to conclude that the LTA4H inhibitors may have therapeutic utility for the disease (IBD) and other inflammatory diseases.

Events that reveal the inflammatory response include the formation of Pro-inflammatory mediator leukotriene B4. Hydrolase LTA4H catalyzes the production of this mediator, and LTA4H inhibitors block the production of Pro-inflammatory mediator LTB4, thereby both the providing the ability to prevent and/or treat leukotriene-mediated conditions such as inflammation. The inflammatory response is characterized by pain, fever, redness, swelling or reduced function or a combination of two or more of these symptoms. From the point of view of the beginning and evolution of inflammation the inflammatory mediated disease or inflammation of the disease or condition include, but are not limited to, acute inflammation, allergic inflammation and chronic inflammation.

Featured guides on inflammation include J.I. Gallin and R. Snyderman, Inflammation: Basic Principles and Clinical Correlates, 3rdEdition, (Lippincott Williams & Wilkins, Philadelphia, 1999); V. Stvrtinova, J. Jakubovsky and I. Hulin, "Inflammation and Fever", Pathophysiology Principles of Diseases (Textbook for Medical Students, Academic Press, 1995); Cecil et al., In Textbook Of Medicine, 18thEdition (W.B. Saunders Company, 1988); and Steadmans Medical Dictionary.

Fundamental retrospective materials and reviews for inflammation and conditions associated with inflammation, can be found, for example, in the following publications: C. Nathan, Points of control in inflammation, Nature 2002, 420:846-852; K.J. Tracey, The inflammatory reflex, Nature 2002, 420:853-859; L.M. Coussens and Z. Werb, Inflammation and cancer, Nature 2002, 420:860-867; P. Libby, Inflammation in atherosclerosis, Nature 2002, 420:868-874; C. Benoist and D. Mathis, Mast cells in autoimmune disease, Nature 2002, 420:875-878; H.L. Weiner and 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 partners in crime, Nature Medicine 2002, 8(11):1211-1217. References included in this is a General description by reference.

Inflammation can be caused by any of a variety of conditions such as asthma, chronic obstructive pulmonary disease (COPD), atherosclerosis, rheumatoid arthritis, multiple [multiple] sclerosis, inflammatory bowel disease (including Crohn's disease and ulcerative colitis) or psoriasis, each of which are characterized by excessive or prolonged inflammation at some stage of its development.

The authors found connection benzoxazol-2-yl, benzothiazol-2-yl and 1H-benzimidazole-2-yl, and their derivatives; and suggest their use as inhibitors of enzymes such as LTA4H enzyme in the formation of proinflammatory mediators, such as the mediator LTB4; and their use for the treatment of inflammatory conditions; and obtaining pharmaceutical compositions for treatment of inflammation.

A brief statement of the substance of the invention

The present invention provides inhibitors of LTA4H enzyme, which have the following General formula (I):

or their enantiomers, diastereoisomers, racemates, hydrates, solvate, or pharmaceutically acceptable salts, esters or amides,

where

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

Y is selected from the group consisting of CH2and;

R4selected from the group consisting of iPMS, OCH3, Cl, F, Br, I, OH, NH2CN, 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 in the specified alkenyl that is associated with the nitrogen has only a simple connection, C3-7the quinil, where the carbon in the specified quinil that is associated with the nitrogen has only a simple connection, With3-7cycloalkyl, optional benzododecinium,5-7cycloalkenyl, -C3-7cycloalkyl1-7of alkyl, -C1-7alkyls3-7cycloalkyl and phenyl, where each of the substituents And independently substituted by 0, 1 or 2 RQand each of these RQDeputy at carbon, which at least one carbon atom removed from the nitrogen;

B) Deputy HetRand;

C) -C1-7alkyls(O)RX, optionally substituted CH2RAror CH2RAr';

D) -C2-5alkyls(O)RXwhere two carbon atoms in the C2-5the alkyl specified-C2-5alkyls(O)Rxwhen valence allows, are part saturated With3-6carbocycle;

E) -C2-5alkylen, where two carbon atoms in the C2-5the alkyl specified-C2-5alkylen when valence allows, are part saturated With3-6carbocycle;

F) -C0-4alkylphenyl,where phenyl in the specified-C 0-4alkylphenyl condensed via two adjacent carbon in the specified phenyl with Rfis benzododecinium;

G) -C0-4alkili6where Ar6represents a 6-membered heteroaryl, attached through a carbon atom and containing one or two heteroatom-N=, and is benzododecinium;

H) -C0-4alkili5where Ar5represents a 5-membered heteroaryl having one heteroatom selected from the group consisting of O, S and >NRYand having 0 or 1 additional heteroatom-N=, optionally containing two carbonyl groups, and optionally benzoannelirovannykh;

I) -C1-4alkili5'where Ar5'represents a 5-membered heteroaryl containing 3 or 4 nitrogen, optionally substituted by RYand with the correct valency position as the point of connection;

J) -C0-4alkili6-6where Ar6-6represents a C0-4the alkyl-linked phenyl, condensed on the provisions allowed by valence with 6-membered heteroaryl where indicated 6-membered heteroaryl has one or two heteroatom-N=;

K) -C0-4alkili6-5where Ar6-5represents a C0-4the alkyl-linked phenyl, condensed on the provisions allowed by valence, 5-membered heteroaryl, and the specified 5-membered heteroaryl has the one heteroatom, selected from the group consisting of O, S and >NRYand the 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-benzimidazole; and

M) SO2With1-4of alkyl;

alternative R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is specified nitrogen accession, and this heterocyclic ring selected from the group consisting of

i) (4-7)-membered heterocyclic ring HetRbwhere specified (4-7)-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the nitrogen attached, and substituted by 0, 1, or 2 substituents at the same or different substituted atoms, said substituents selected from the group consisting of-RY, -CN, -C(O)RY, -C0-4alkyls2RY,

-C0-4alkyls(OH)2RY- 0-4ORY- 0-4alkyls(O)NRYRZ,

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

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

-Csub> 0-4NRYC(O)NRYRZ, -C0-4NRYC(S)NRYRZ, -NRYC(O)CO2RY,

-NRYRZ, -C0-4NRWSO2RY1,3-dihydroindol-2-on-1-yl,

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

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

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

-C0-4alkyls(O)N(RY)(SO2RY), -C0-4the N(RY)(SO2)NRYRY,

-C0-4the N(RY)(SO2)NRYCO2RY, halogen,

ii) (5-7)-membered heterocyclic ring HetRwithwhere specified (5-7)-membered heterocyclic ring has one additional heteroatom, remote from the specified nitrogen attaching at least one carbon atom, with specified additional heteroatom selected from the group consisting of O, S(=O)0-2and >NRMand where specified (5-7)-membered heterocyclic ring HetRwithis 0 or 1 carbonyl group and is substituted by 0, 1, or 2 substituents at the same or different substituted hydrocarbons, these substituents selected from the group consisting of-C(O)RY, -CO2RY, -C3-4alkyls2RYand 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 by 0 or 1 carbon Deputy, selected from C0-4RZ, -C0-4SRY, -C0-4alkyls2RYand Deputy HetRand; and

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

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

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

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

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

where

Deputy HetRandrepresents (4-7)-membered heterocyclic ring attached via a carbon atom and containing the group >NRMas heteroatom, where said heteroatom is separated from the specified attachment point via a carbon atom, at least 1 additional carbon atom;

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

RLselected from the group SOS is oasa of CO 2RSand-C(O)NRSRS';

RMselected from the group consisting of RZ, indol-7-yl, -SO2RY, -C3-4alkyls2RY, -CO2RY, -C(O)NRZORY, -C(O)RY, -C(O)C1-4ORY, -C0-4alkyls(O)NRSRS', -C0-4alkyls(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 and-C0-4alkyls(O)N(RY)(SO2RY), each optionally substituted by 1, 2 or 3 substituents RN;

RNselected from the group consisting of OCH3, Cl, F, Br, I, OH, NH2CN, CF3CH3, OC(O)CH3and NO2;

RRselected from the group consisting of RY, -C2-4ORY, RAr, -C1-2alkyls2RY, -C1-2CONRSRS', indol-7-yl and-SO2With1-4of alkyl;

RQselected from the group consisting of fluorine, chlorine, bromine, iodine,

trifloromethyl, trichloromethyl, -CN, -C1-4of alkyl, -C0-4RAr,

-C0-4RAr', -C0-4ORY, -C0-4alkyls2RY, -C0-4NRYRZ,

-C0-4NRYCORY, -C0-4NRYCONRYRZ, -C0-4NRYSO2RYand

-C0-4SRY;

Sand RS'independently selected from the group consisting of H, -C1-4the alkyl and-C0-4alkylphenyl; alternatively, RSand RS'taken together with the nitrogen to which these RSand RS'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 specified additional heteroatom separated by at least two carbons from the specified nitrogen to which these RSand RS'connected, and provided that when RYrepresents a C0-4RArthen RArnot substituted RL;

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

RXselected from the group consisting of-ORY, -NRYRZ, -C1-4the alkyl and C0-4RAr;

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

RZselected from the group consisting of RY- 2-4ORY, -C1-2alkyls2RY, -C1-2alkyls(O)NRSRS' and-C2-4NRSRS';

when RYand RZattached to the nitrogen, RYand RZselected as defined above, or RYand RZin atie together with the nitrogen associated with RYand RZform 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 specified (4-7)-membered heterocyclic ring HetRdis 0 or 1 when the valence allows, a carbon atom, is substituted by at least one of RM, -CO2H, and-C0-1ORY;

RAris a piece that is attached via a carbon atom, and the specified fragment selected from the group consisting of phenyl, pyridyl, pyrimidinyl and pyrazinyl, where each carbon atom, when valence allows, in each of these fragments independently substituted by at least one of the substituents: either 0, 1, 2, or 3 RNor 0 1 or RL;

RAr'represents (3-8)-membered cyclic ring having 0, 1 or 2 heteroatoms selected from the group consisting of O, S, N and >NRYhaving 0, 1 or 2 bonds, having 0 or 1 carbonyl group, where each atom, when valence allows, in each of these circular rings is independently substituted by 0, 1 or 2 RTo;

and

Rfis a linear (3-5)-membered hydrocarbon group having 0 or 1 unsaturated carbon-carbon bond and having 0 or 1 carbonyl group.

Variants of the embodiment of the present invention include novel compounds which are inhibitors of LTA4H enzyme and have the General formula (II):

or their enantiomers, diastereoisomers, racemates, tautomers, hydrates, solvate, or pharmaceutically acceptable salts, esters or amides,

where

R4, R6X and Y are such as defined for the compounds of formula (I), R2'defined as R2for the compounds of formula (I), and R3'defined as R3for the compounds of formula (I),

provided that

(a) the R2'and R3'in addition, meet the following conditions:

(e1): the R2'and R3'both are not H when Y is Oh and X represents S;

(e2): when Y is a bond, X represents N and the specified R2'and R3'are part of a primary or secondary amino group, then the specified R2'and R3'not selected from the group consisting of H and methyl, (for example, the choice of R2'which is H, and R3'which stands thus invalid; the choice of R2'which stands and R3'which is N, thus invalid; the choice of R2'which is N, and R3'which is N, thus invalid; however, the choice of R2'which stands, and R3', who stands in stage is Tim);

(e3): the R2'and R3'taken together with the nitrogen to which they are bound, do not form pieperazinove group, when X is O and Y is one of O and CH2;

(e4): the R2'and R3'taken together with the nitrogen to which they are bound, do not form piperidino group, which monogamist saturated 6-membered cyclic group, when X is O and Y is one of O and CH2;

and

(e5): the R2'and R3'taken together with the nitrogen to which they are bound, do not form any substituted piperidino group or substituted piperazino group where the specified substituted piperidino group or specified substituted pieperazinove group substituted in position 4 by the Deputy XG, with the specified XG has the structure

where n=0, 1, and when ne=1, then XL is a1-6alkyl, OSG represents O or S, and XR1and XR2taken together with the nitrogen to which they are attached, form one of piperidino group, piperazino group, morpholino group, thiomorpholine group and pyrrolidino group, or each of the XR1and XR2taken independently represent one of H, C1-6of alkyl, aryl, aralkyl,3-8cycloalkyl,3-8cycloalkyl-C1-6of alkyl, heteroalkyl, heteroaryl-C1-6is Lila, geterotsiklicheskie and heteroseksualci-C1-6of alkyl, where the aryl, aralkyl, cycloalkyl, heteroaryl or heteroseksualci may be optionally substituted by one or more substituents, independently selected from halogen, hydroxy, C1-6of alkyl, C1-6alkoxy, kalogeropoulos1-6of alkyl, kalogeropoulos1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or geterotsiklicheskie; and

(b) further provided that when X represents S and Y represents Oh, then one of R2'and R3'is not XCG, when the other represents C1-6alkyl, where XCG is a group

where HC16 represents one of H1-6of alkyl, Halogens1-6of alkyl, allyl and C1-6alkoxymethyl, and GO is a group associated with the carbon atom, which has a Deputy =O, forming aminogroup (>N-C(O)-) with nitrogen, which is linked to a specified GO group.

Isomeric forms of the compounds of formulas (I) and (II) and their pharmaceutically acceptable salts, amides and esters are included in the scope of the present invention, and this implies that the link in this description to one of such isomeric forms include at least one of such isomeric forms. The person skilled in the art it will be obvious that some compounds in this invention may exist, for example, in one isomeric form, while other compounds may exist in the form of a regioisomeric mixture.

Assume regardless, specify whether explicitly or not in any part of the description and claims that each designation Deputy and member in the context of this invention are doing regardless of the designation of any other member and substituent, unless otherwise stated. As a first example according to the terminology of the Deputy when the Deputy S1examplerepresents one of the S1and S2and Deputy S2examplerepresents one of the S3and S4then these designations refer to variants of the embodiment of the present invention defined according to the election of 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 one of these elections. Accordingly, for brevity, but not to limit use the shortened term is a logic “S 1examplerepresents one of the S1and S2,and S2examplerepresents one of the S3and S4”. Above is the first example in the terminology of the Deputy, which stated in General terms, as is implied, illustrates the various described designation Deputy R. Preceding symbol, given for substituents extends, when applicable, to members such as X, Y, Z and W, and the index n.

In addition, in cases where more than one designation is given to any member or Deputy, the variants of embodiment of the present invention include various groups, which can be created of these designations, taken independently, and their equivalents. As a second example according to the terminology of the Deputy, if described, Deputy Sexamplerepresents one of the S1, S2and S3this list relates to variants of the embodiment of the present invention, for which 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; Sexamplebefore the hat is one of S 1, S2and S3; and Sexampleis any equivalent of each one of these elections. Accordingly, for brevity, but not to limit use shorthand terminology "Sexampleis a from S1, S2and S3". Above the second example in the terminology of the Deputy, which stated in General terms, as is implied, illustrates the various described designation Deputy R. Preceding symbol, given for substituents extends, when applicable, to members such as X, Y, Z and W, and the index n.

It is assumed that the terminology "Ci-j"where j>i, when applied to a class of substituents refers to variants of the embodiment of the present invention, for which independent is implemented every one of the number of carbon atoms, from i to j, including i and j. As an example, the term1-3applies independently to variants of the embodiments that have one carbon (C1), variants of the embodiments that have two carbon (C2and variants of the embodiments that have three carbon (C3).

The termn-malkyl refers to an aliphatic chain, regardless of whether straight or branched, with the total number N of carbon atoms in the chain, which satisfies n≤N≤m, where m>n.

When any variable related to C is the election agent, member (element) of the compound or the index occurs more than once, the full range of designations, as implied, is applied in every instance of its use, regardless of the particular(s) indicate(s) in any other case use this variable.

In accordance with the above interpretive considerations concerning notation and terminology imply that the explicit reference to the many suggests, where it is chemically significant and, if not specified otherwise, an independent reference to variants of realization of such sets, and a link to each one of the possible variants of embodiment of subsets specified explicitly.

The present invention also provides methods for inhibiting the activity of LTA4H enzyme the above compounds, and pharmaceutical compositions containing such compounds, and methods of using such compositions for the treatment or prevention of conditions which are mediated by LTA4H enzyme activity.

The pharmaceutical compositions according to the present invention include at least one of the compounds according to this invention. If the composition includes more than one of the proposed connection, therapeutically effective amount can be jointly effective amount. As such inhibitors of LTA4H enzyme, connect the indicators of the composition according to this invention are used for the prevention, inhibition or treatment of inflammation.

In addition, this invention provides a pharmaceutical composition for the treatment or prevention of LTA4H-mediated condition in a subject, containing a therapeutically effective amount of at least one LTA4H modulator selected from compounds of formulas (I), (II) and (III), their enantiomers, diastereoisomers, racemates, pharmaceutically acceptable salts, amides and esters. In addition, this invention provides a pharmaceutical composition for inhibiting the inflammatory reaction in the subject, containing a therapeutically effective amount of at least one LTA4H inhibitor selected from compounds of formulas (I), (II) and (III), their enantiomers, diastereoisomers, racemates, pharmaceutically acceptable salts, amides and esters. This invention additionally provides anti-inflammatory composition comprising a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulas (I), (II) and (III), their enantiomers, diastereoisomers, racemates, pharmaceutically acceptable salts, amides and esters.

This invention provides methods of treating or preventing inflammation in a subject comprising administration to the subject in connection with inflammatory reaction Pharma is eticheskoi composition, which contains a therapeutically effective amount of at least one anti-inflammatory compound selected from compounds of formulas (I), (II) and (III), their enantiomers, diastereoisomers, racemates, pharmaceutically acceptable salts, amides and esters. The invention also provides methods of treatment or prevention of LTA4H-mediated condition in a subject comprising administration to the subject a pharmaceutical composition that contains a therapeutically effective amount of at least one LTA4H modulator selected from compounds of formulas (I), (II) and (III), their enantiomers, diastereoisomers, racemates, pharmaceutically acceptable salts, amides and esters. In addition, the invention provides methods for inhibiting inflammation in a subject comprising administration to the subject a pharmaceutical composition that contains a therapeutically effective amount of at least one LTA4H inhibitor selected from compounds of formulas (I), (II) and (III), their enantiomers, diastereoisomers, racemates, pharmaceutically acceptable salts, amides and esters.

This invention provides methods for treatment, prevention and/or inhibition of conditions that are associated with and/or inflammation, such as any or many of the following conditions: asthma, chronic about the reconstructive lung disease (COPD), atherosclerosis, rheumatoid arthritis, multiple [multiple] sclerosis, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), or psoriasis, which are each characterized by excessive or prolonged inflammation at some stage of the disease.

Additional features (distinctive features and advantages of this invention become apparent from the following detailed description, including the examples and the appended claims.

Detailed description of the invention

The present invention relates to compounds of formula (I), (II) or (III), defined above, their enantiomers, diastereomers, racemates, pharmaceutically acceptable salts, Amida and esters, pharmaceutical compositions that contain at least one of the above compounds, methods of use thereof, including the treatment and/or prevention of conditions such as States that are mediated by LTA4H, and methods of producing the above-mentioned compositions.

The following terms are defined below and by using them throughout the disclosure of the invention.

"Alkyl" includes hydrocarbons with straight and branched chain with at least one remote hydrogen, forming a radical group. Alkyl groups include methyl, ethyl, sawn, and propileno, boutelou, isobutylene, tert-boutelou, 1-methylpropyloxy, pentelow, isopentanol, second-pentelow, hexeline, heptylene, octillo etc. Alkyl does not include cycloalkyl.

"Alkenyl" includes the above hydrocarbon radicals, straight and branched chain with at least one carbon-carbon double bond (sp2). If not mentioned specifically by using a prefix that indicates the number of carbon atoms, alkenyl include 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-Danila etc.

"Quinil" includes the above-mentioned hydrocarbon radicals, straight and branched chain with at least one triple bond (sp). If not mentioned specifically by using a prefix that indicates the number of carbon atoms, alkinyl include ethinyl, propinyl, butinyl and pentenyl. Hydrocarbon radicals, having a mixture of double bond and triple connections, such as 2-penten-4-inyl, also covered by the term “quinil”.

"Alkoxy" includes an alkyl group with straight and branched chain with limit oxygen linking the alkyl group with the remainder of the molecule. Alkoxy includes methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, intoxi etc. "Aminoalkyl", "thioalkyl and sulfonylated" anal is Hecny alkoxy except that the terminal oxygen atom of the alkoxy substituted respectively the NH (or NR), S and SO2.

If not mentioned specifically by using a prefix that indicates the number of carbon atoms, cycloalkyl" includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl etc.

If not mentioned specifically by using a prefix that indicates the number of members in a circular structure, the term "heterocyclyl", "heterocyclic" or "heterocycle" represents a (3-8)-membered aromatic, saturated or partially saturated single or condensed ring system which consists of carbon atoms, where the heteroatoms selected from N, O and S. Examples of heterocycles include thiazolyl, furyl, pyranyl, isobenzofuranyl, pyrrolyl, imidazolyl, pyrazolyl, isothiazolin, isoxazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolizinyl, isoindolyl, indolyl, indazoles, purinol, hinely, furutani, pyrrolidinyl, pyrrolyl, imidazolidinyl, imidazolyl, pyrazolidine, pyrazoline, piperidyl, piperazinil, indolinyl and morpholinyl. For example, preferred heterocycles or heterocyclic radicals include morpholinyl, piperazinil, pyrrolidinyl, pyridyl, cyclohexylamino, cycloheptylamine and more preferably piperidyl.

The position of substitution is indicated in conventional terms. For example, the R, the provisions of the substitution groups of the piperidine and piperazine are numbered as follows:

“Carbocycle” is cycloalkyl or partially saturated cycloalkyl that is not a benzo.

"Aryl" includes phenyl, naphthyl, biphenylyl, tetrahydronaphthyl and the like, each of which may be optionally substituted. Aryl also includes arylalkyl groups such as benzyl, phenethyl and phenylpropyl. Aryl includes the cyclic system containing optionally substituted 6-membered carbocyclic aromatic ring, while this system may be bicyclic; bridge and/or condensed. The 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. Examples illustrating heteroaryl are thienyl, furanyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, benzothiazyl, benzofuranyl, benzimidazolyl, benzoxazolyl, benzothiazolyl.

"Halogen" includes fluorine, bromine, chlorine, bromine and iodine, and preferred is fluorine or chlorine.

The term "carbonyl” refers to the >C=O, so that when this term is used to describe chastize or a cyclic structure, we mean that the carbon in the carbonyl group is one of the carbons such chain or cyclic structure.

As is customary in conventional chemical nomenclature, phenyl group called "phenyl" or "Ph".

Assume that substitutions and combinations of substitutions listed in this description, regardless of whether they are explicitly or not, are substitutions that are consistent with the valence of the member (joint member), subject to substitution. Terms such as "valid valency position, when the valence allows, and their morphological variations used in this sense. For example, the term "valid value" when applied to a carbon refers to the valency four carbon; refers to the three valence of nitrogen when applied to the nitrogen; and this term refers to the four relations nitrogen member, which has a positive electric charge. Options allowed by valence, are in the competence of the specialist in this field.

"Patient" or "subject" includes mammals, such as humans and animals (e.g. dogs, cats, horses, rats, rabbits, mice, non-human primates), in need of supervision, experiment, treatment or prevention in connection with the relevant disease or condition. Preferably the patient is a man.

<> "Composition" includes a product containing specific components in specific amounts, including their content in effective amounts, as well as any product which is directly or indirectly the result of combinations of specific components in specified quantities.

"Therapeutically effective amount" or "effective amount" and grammatically related terms means the amount of active compound or pharmaceutical agent that elicits the biological or medicinal response in a tissue system, animal or human that is being hunted by a researcher, veterinarian, doctor or other Clinician, and this response includes the relief of symptoms of the disease or disorder to be treated.

Table abbreviations
The termReduction
TetrahydrofuranTHF
N,N-DimethylformamideDMF
N,N-DimethylacetamideDMA
The sulfoxideDMSO
t is em-Butylcarbamoyl BOC
Bovine serum albuminBSA
High performance liquid chromatographyHPLC
Thin-layer chromatographyTLC

The compounds of formula (I), (II) or (III) include compounds that match any of the combinations of the definitions presented herein, and equivalents.

It should be borne in mind that some compounds described herein, are chiral and/or have geometric isomeric centres (E - and Z-isomers. The present invention encompasses all such optical isomers, including diastereoisomeric and racemic mixtures, geometric isomers, which have activity which distinguishes the compounds according to this invention. In addition, some compounds described herein can exist in solvated forms, and resolutiony forms. It should be borne in mind that the invention encompasses all such solvated and nonsolvated forms, which have activity which distinguishes the compounds according to this invention. Compounds according to the invention which have been subjected to transformation is the Oia to betray them the ability to be detected by some of the analytical method, also included in the scope of this invention. An example of such compounds is an isotope-labeled compound, such as labeled18F-isotope compound, which can be used as a probe (indicator) in (diagnostic) methods for the detection and/or image acquisition, such as positron emission tomography (PET) and single photon emission computed tomography (SPECT). Another example of such compounds is the isotope-labeled compound, such as compound labeled with deuterium and/or tritium, which can be used in studies of the kinetics of the reactions.

It is clear that substitutions and combinations of substitutions listed in this description, regardless of whether they are explicitly or not, include the overrides that are in accordance with the valence of the member (joint member), subject to substitution. Terms such as "valid valency position, when the valence allows, and their morphological variations used in this sense. For example, the term "valid value" when applied to a carbon refers to the valence of four; refers to the three valence N, when applied to the nitrogen; and this term refers to the four relations nitrogen member, which has a positive electric charge. Options allowed by valence, are to the authorized specialist in this field.

The term “Pharmaceutically acceptable salts, amides or esters them” refers to those forms of salts, amides and esters of the compounds of this invention which are obvious to a pharmacist / chemist, i.e. those that are non-toxic and which may favorably affect the pharmacological characteristics of these compounds according to this invention. Such compounds have favorable pharmacological properties, will be obvious to a pharmacist / chemist, i.e. are compounds that are non-toxic and which possess pharmacological characteristics that provide sufficient palatability (nice flavor), absorption (absorption, distribution, metabolism and excretion. Other factors, more practical in nature, which are also important when choosing include the cost of the starting substances, ease of crystallization, yield, stability, hygroscopicity and fluidity of the obtained bulk (mass) of the medicinal product.

Typical acids and bases that can be used to obtain pharmaceutically acceptable salts, include the following:

acids, including acetic acid, 2,2-dichloracetic acid, acylated amino acids, adipic acid, alginic acid, ascorbic acid, L-aspartic is islote, benzosulfimide 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, reklamowy acid, dodecylthio acid, ethane-1,2-disulfonate acid, econsultancy acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactarate acid, entityname acid, glucoheptonate acid, D-gluconic acid, D-glucuronic acid, L-glutamic acid, b-oxoglutaric 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-almond acid, methanesulfonate acid, naphthalene-2-sulfonic acid, naphthalene-1,5-disulfonate acid, 1-hydroxy-2-naphthoic acid, nicotinic acid, nitric acid, oleic acid, Orotava acid, oxalic acid, palmitic acid, pambou acid, phosphoric acid, L-pyroglutamic acid, salicylic acid, 4-aminosalicylic acid, sabotinova acid, stearic acid, succinic acid, sulfuric acid, tannic acid, (+)-L-sour wine is from, ticinobuy acid, p-toluensulfonate acid and undecylenoyl acid; and bases, including 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)pyrrolidine, secondary amine, sodium hydroxide, triethanolamine, tromethamine and zinc hydroxide.

See, for example, S.M. Berge, et al., "Pharmaceutical Salts", J. Pharm. Sci., 1977, 66:1-19, the contents of which are incorporated into this description by reference. Examples of suitable esters include C1-7alkalemia, C5-7cycloalkyl, phenyl, substituted phenyl and panels1-6alkalemia esters. Preferred esters include methyl esters.

In the scope of the present invention includes prodrugs of the compounds according to this invention. Typically, these prodrugs are functional derivatives of the compounds which can easily be transformed in vivo into the required compound. Therefore, in the methods of treatment according to this invention, the term "introduction" will cover the treatment described in this description of disorders specifically disclosed in the present description connection or a connection that may not be a revelation is about specifically, but which is converted in vivo to a specific compound after administration to the patient. Conventional methods of selecting and obtaining the appropriate derivative prodrugs described, for example, in "Design of Prodrugs", ed. H. Bundgaard, Elsevier, 1985.

Embodiments of the present invention, where X represents Oh, get in accordance with synthetic methods presented in General terms in schemes A-D and F-L, show inhibitory activity against LTA4H and selected from the group consisting of:

ExampleConnection
112-[4-(2-piperidine-1-ylethoxy)phenoxy]benzoxazol;
13(1-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
141-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
16{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}dibutylamine;
21(1-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-2-yl)methanol;
271-{3-[4-(benzoxazol-2-yloxy)phenoxy]propyl}-4-phenylpiperidine-4-ol;
281-{3-[4-(benzoxazol-2-yloxy)phenoxy]propyl}-4-benzylpiperidine-4-ol;
292-[4-(2-piperidine-1-retil)phenoxy]benzoxazol;
35{3-[4-(benzoxazol-2-yloxy)phenyl]propyl}cyclohexylethylamine;
361-{3-[4-(benzoxazol-2-yloxy)phenyl]propyl}piperidine-4-ol;
401-{3-[4-(benzoxazol-2-yloxy)phenoxy]-2-hydroxypropyl}-4-phenylpiperidine-4-ol;
41ethyl ester of 1-[2-(4-benzoxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
442-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]benzoxazol;
45{3-[4-(benzoxazol-2-yloxy)phenoxy]propyl}dimethylamine;
46{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}dimethylamine;
472-[4-(2-azepin-1 ylethoxy)phenoxy]benzoxazol;
531-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
54 {2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
552-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}benzoxazol;
561-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-carbonitrile;
571-(1-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)Etalon;
582-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}benzoxazol;
591-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
601-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
611-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-(4-chloro-3-triptoreline)piperidine-4-ol;
621-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
63{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
64{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}cyclopropanemethylamine is;
65{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}butylethylamine;
662-({2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}benzylamino)ethanol;
672-{4-[2-(4-benzylpiperidine-1-yl)ethoxy]phenoxy}benzoxazol;
68(1-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol;
692-({2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}propylamino)ethanol;
772-[4-(2-azetidin-1 ylethoxy)phenoxy]benzoxazol;
78N-(1-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-2-phenylacetamide;
79ethyl ester of 1-{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-3-carboxylic acid;
862-{4-[3-(4-phenylpiperazin-1-yl)propoxy]phenoxy}benzoxazol;
881-{2-[4-(benzoxazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-ol;
89{2-[4-(benzoxazol-2-yloxy)phenyl]ethyl}College militiamen;
902-[4-(2-pyrrolidin-1-retil)phenoxy]benzoxazol;
912-[4-(2-azepin-1-retil)phenoxy]benzoxazol;
92{2-[4-(benzoxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
93{2-[4-(benzoxazol-2-yloxy)phenyl]ethyl}dibutylamine;
941-{2-[4-(benzoxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
96methyl ester 1-{2-[4-(benzoxazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
1161-{3-[4-(benzoxazol-2-yloxy)phenyl]propyl}-4-phenylpiperidine-4-ol;
1202-[4-(3-piperidine-1-ylpropyl)phenoxy]benzoxazol;
121{3-[4-(benzoxazol-2-yloxy)phenyl]propyl}dibutylamine;
122{3-[4-(benzoxazol-2-yloxy)phenyl]propyl}cyclopropanemethylamine;
1351-[4-(benzoxazol-2-yloxy)phenoxy]-3-pyrrolidin-1-improper-2-ol;
1361-[2-(4-benzoxazol-2-ylmethylene)ethyl]-4-phenylpiperidine-4-ol;
137amide 1-[2-(4-benzoxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid;
2712-(4-piperidine-1-ylmethylene)benzoxazol;
4812-[4-(2-morpholine-4-ylethoxy)phenoxy]benzoxazol and
484{2-[4-(benzoxazol-2-yloxy)phenoxy]ethyl}diethylamine.

Other variants of the embodiment of the present invention, where X represents S, receive in accordance with synthetic methods presented in General terms in schemes A-G and I-L, show inhibitory activity against LTA4H and selected from the group consisting of:

td align="center"> 84 2-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)-1-pyrrolidin-1-ylatason;
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 what Islami;
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-diazaspiro[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)phenyl]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;
70 1-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-ol;
71{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
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;
2-(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-ol;
103methyl ester 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid;
104 amide 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-carboxylic 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-diazaspiro[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-pyrrolidin-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 methyl ether (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-yloxy)phenoxy]ethyl}piperazine-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;
173 3-[{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;
182
183(R)-1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-3-carboxylic acid;
1841-(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 sour is a;
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-yl)phenol;
2052-(4-{2-[4-(4-methoxyphenyl)piperazine-1-yl]ethoxy}phenoxy)benzothiazole;
2062-{4-[2-(5-piperidine-4-alterator-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 acid
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;
212 1-({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;
2143-({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-methylsulfanyl razol-1-yl)ethoxy]phenoxy}benzothiazole;
2232-[4-(2-tetrazol-2-ylethoxy)phenoxy]benzothiazole;
2242-[4-(2-tetrazol-1 ylethoxy)phenoxy]benzothiazole;
225(R,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)b is nil]piperidine-4-yl}-2-hydroxyacetate;
2541-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-he;
255N-{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-(benzothiazolinone)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;
2692-[4-(benzothiazol-2-yloxy)phenyl]ethylamine hydrochloride;
2702-(4-{2-[4-(1H-tetrazol-5-yl)piperidine-1-yl]ethoxy}phenoxy)benzothiazole;
2712-(4-piperidine-1-ylmethylene)benzoxazol;
272[4-(benzothiazol-2-yloxy)benzyl]cyclohexylethylamine;
273[4-(benzothiazol-2-yloxy)benzyl]cyclopropanemethylamine;
274amide 1-[-(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)benzyl]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 acid
280N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}sulphonamide hydrochloride
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;
284 tert-butyl ether [2-({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}carbarnoyl)cyclobutyl]carbamino acids;
285the dihydrochloride {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acids;
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-diazaspiro [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-(benzothiazol-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-diazaspiro[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}piperidine-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-(benzotriazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)morpholine-4-ylmethanone;
3141-(4-{2-[4-(benzothiazol-2-and the hydroxy)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-yl) - Rev. XI)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-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-(benzodiaz the l-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-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he;
337tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino 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-methylisothiazoline;
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-diazaspiro[4.5]Decan-4-one;
3488-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-diazaspiro[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-(Ben is thiazol-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-(benzo is a thiazol-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-methanesulfonylaminoethyl-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 key is lots;
3771'-{2-[4-(benzothiazol-2-yloxy)phenoxy]ethyl}-[1,4']bipyridinyl-4-carboxylic acid;
378{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine;
379salt triftormetilfullerenov acid 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-2-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(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;
3883-[5-(1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)tetrazol-1-ylpropionic;
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-3-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;
1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carbonitrile;
3972-(4-{2-[4-(1H-[1,2,3]triazole-4-yl)piperidine-1-yl]ethyl}phenoxy)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}cyclepro is ylmethylamino)propyl]ndimethylacetamide;
406[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide morpholine-4-carboxylic acid;
407N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide;
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-methylpiperidin-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)wt is Jana 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-[-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]benzamide;
425N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-4-chlorobenzamide;
426N-[3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]methanesulfonamide;
427salt triftormetilfullerenov acid [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)Fenox is]ethyl}cyclopropylamino)butyric acid;
4341-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-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)-3-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-(benzothiazolinone)benzyl]piperidine-4-yl}-2-hydroxyacetate;
451N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-triptorelin;
4522-[4-(1,1-diocletianopolis-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 {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-(is isothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
4651-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-proprotein;
466propyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
4671-{1-[4-(benzothiazolinone)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]piperidin the-4-yl}-N'-hydroxyguanidine;
476isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
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.

Additional variants of the embodiment of the present invention, where X represents NR5where R5is one of H and CH3receive in accordance with synthetic methods presented in General terms in schemes A-C, F, G and J-L, show inhibitory activity against LTA4H, and selected from the group consisting of:

ExampleConnection
371-{2-[4-(1H-benzothiazol-2-idoxifene]ethyl}-4-phenylpiperidine-4-ol;
38{2-[4-(1H-benzothiazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine;
39cyclohexylethyl{2-[4-(1-methyl-1H-benzimidazole-2-yloxy)phenyl]ethyl}amine;
1171-{2-[4-(1H-benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-bromophenyl)piperidine-4-ol;
1181-{2-[4-(1H-benzothiazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol;
1191-{2-[4-(1H-benzothiazol-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol;
123{2-[4-(1H-benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine;
1242-[4-(2-pyrrolidin-1-retil)phenoxy]-1H-benzimidazole;
1252-[4-(2-azepin-1-retil)phenoxy]-1H-benzimidazole;
126{2-[4-(1H-benzothiazol-2-yloxy)phenyl]ethyl}dibutylamine;
1271-{2-[4-(1H-benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ol;
128methyl ester 1-{2-[4-(1H-benzothiazol-2-yloxy)phenyl]the Teal}piperidine-4-carboxylic acid;
129{2-[4-(1H-benzothiazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine;
1302-{4-[2-(4-methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzimidazole;
1312-{4-[2-(2-ethylpiperidine-1-yl)ethoxy]phenoxy}-1H-benzimidazole;
1322-[4-(2-piperidine-1-ylethoxy)phenoxy]-1H-benzimidazole;
133(1-{2-[4-(1H-benzimidazole-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol;
1341-{2-[4-(1H-benzimidazole-2-yloxy)phenoxy]ethyl}piperidine-4-ol;
1382-[4-(2-azepin-1 ylethoxy)phenoxy]-1H-benzimidazole;
139{3-[4-(1H-benzothiazol-2-yloxy)phenoxy]propyl}dimethylamine;
1402-[4-(2-pyrrolidin-1 ylethoxy)phenoxy]-1H-benzimidazole;
141{2-[4-(1H-benzimidazole-2-yloxy)phenoxy]ethyl}diethylamine;
1422-[4-(2-morpholine-4-ylethoxy)phenoxy]-1H-benzimidazole;
230 2-[4-(2-piperidine-1-retil)phenoxy]-1H-benzimidazole;
2311-(1-{2-[4-(1H-benzimidazole-2-yloxy)phenoxy]ethyl}piperidine-4-yl)pyrrolidin-2-he;
480(1-{2-[4-(1H-benzimidazole-2-yloxy)phenoxy]ethyl}piperidine-4-yl)methanol and
485ethyl ester of 1-{2-[4-(1H-Benzimidazole-2-yloxy)phenoxy]ethyl}piperidine-4-carboxylic acid.

Some preferred compounds occurring in the context of this invention, include the following:

methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acids;
2712-(4-piperidine-1-ylmethylene)benzoxazol;
5272-(2-fluoro-4-piperidine-1-ylmethylene)benzoxazol;
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)of gasoline is]piperidine-4-yl}-2-hydroxyacetate;
2541-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-he;
255N-{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]piperidine-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;
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)is ensil]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-methanesulfonylaminoethyl-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;
N-{l-[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;
4341-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-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)be the ZIL]cyclopropylamino}propyl)-3-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-trifurcata the ID;
4522-[4-(1,1-diocletianopolis-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 {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 ether {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;
473
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-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
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;
4861'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipyridinyl;
487{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}tetrahydrofuran-2-yl)methanon;
489tert-butyl ether ({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acids;
490tert-butyl ether 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
4911-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine;
4922-(4-piperazine-1-ylmethylene)benzothiazole;
493amide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
4942-[4-(4-benzolsulfonate-1-ylmethyl)phenoxy]benzothiazole;
495C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
4962-(2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-oxoethyl)Cyclopentanone;
497ethyl ester {4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
4984-(benzothiazol-2-yloxy)benzyl ether of 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyric acid;
4991-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)pyrrolidin-2-he;
500 tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)carbamino acids;
501(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)amide tetrahydrofuran-2-carboxylic acid;
5021-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-4-hydroxypyrrolidine-2-he;
503tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl) - carbamino acids;
504N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine;
505{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide econsultancy acids;
5061-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrole-2,5-dione;
507tert-butyl ether ({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acids;
508{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
5091-[4-(benzothiazol-2-yloxy)benzyl]p is perazin-2-carboxylic acid;
510[4-(benzothiazol-2-yloxy)benzyl]methylamine;
511benzothiazol-2-yl{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amine;
512tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)carbamino acids;
5134-({[4-(benzothiazol-2-yloxy)benzyl]methylamino}methyl)phenol;
514N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-methylpropane-1,3-diamine;
515(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propellerblades)methyl ester acetic acid;
516N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-2-hydroxyacetamido;
517N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)methanesulfonamide;
5186-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
5196-methoxy-2-(4-piperidine-1-ylmethylene)benzothiazole;
520 dimethylamide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-sulfonic acid;
5212-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-pyrrolidin-1-ylatason;
5222-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-morpholine-4-ylatason;
523{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}thiophene-2-ylmethanone;
5244-methyl-2-(4-piperidine-1-ylmethylene)benzothiazole;
5254-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
5262-[4-(4,4-deformability-1-ylmethyl)phenoxy]benzothiazole;
528{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acids;
529[4-(benzothiazol-2-yloxy)benzyl]methyl(1-methylpiperidin-4-yl)amine;
5303-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propionitrile;
5314-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-he;
5322-[4-(3-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
533({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamoyl)methyl ester acetic acid;
534N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxy-N-methylacetamide;
536ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
4882-(4-piperidine-1-ylmethylene)-1H-benzimidazole;
5351-[4-(1H-benzimidazole-2-yloxy)benzyl]piperidine-4-carboxylic acid.

The above compounds were obtained as described in detail in the present description, or for those compounds that are not accompanied by a direct description of how they were obtained, their getting consequential to the changes illustrated receipts, presented in this description, which can be carried out, in the light of the present description, combined with the skill of a specialist in this field.

Compounds according to this invention can be obtained according to the schemes of the reactions described below. The diagrams represent two of the main clause is dhoda to the synthesis of target compounds, both direct way starting from either end of the molecule. Specialists in this field will be obvious that some compounds are more suitable to obtain according to one scheme of reactions compared to the other.

To obtain this description of the various compounds can be used starting materials, bearing, ultimately, the desired substituents, however, on the basis of expediency you can use schema reactions with or without protection. Original products can be obtained from commercial sources or synthesized by methods known to experts in this field. An alternative may be necessary instead of the final desired substituent to use the appropriate group that can be present in the reaction scheme and replace if necessary the desired substituent. Any product containing a chiral center can be separated into its enantiomers by conventional methods.

Options embodiments of the methods illustrated in this description, include, if it is chemically appropriate, one or several stages, such as hydrolysis, halogenoalkane, protect and unprotect. These stages can be carried out in the light provided in this guidance and subject to the usual qualifications of the specialist in this field.

During assests is of any of the methods of preparing compounds according to this invention may be necessary and/or desirable to protect sensitive or reactive groups on any of the molecules, with regard to response. In addition, the compounds of this invention can be modified through the use of protective groups; such compounds, precursors or prodrugs, are also included in the scope of the present invention. This can be achieved using conventional 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. Protective groups can be removed at a suitable subsequent stage using methods known in this field.

Scheme And

With regard to the scheme And where n is 1 or 2, commercially available 4-benzyloxyphenol A1 alkylate aminoalkylindole A2; private aminoalkylated are commercially available. The reaction can be carried out in a wide temperature range, including room temperature and a more elevated temperature, in the presence of an inorganic base used, as is known, to facilitate the flow O-alkylation, such as, but not limited to, K2CO3Cs2CO3and a mixture of them (J. Med. Chem, 1997, 40, 1407-1416). Suitable solvents include, but are not limited to, DMF. Removal of benzyl groups on A3 can be carried out using catalytic conditions, hidrogenesse is, well-known specialists in this area (Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 3rded.; John Wiley & Sons: New York, 1999.). Suitable catalysts include, but are not limited to, Pd on carbon (Pd/C), in solvents such as ethyl acetate, alcohols and mixtures of them. Examples of alcohols include, but are not limited to, CH3HE, ethanol, i-D. Such reactions typically occur at room temperature. Removal of benzyl groups on A3 can be performed using several embodiments, for example using the conditions of recovery or transfer hydrogenation with hydrogen under suitable temperatures. For example, the recovery of hydrogen in the process of dissolution of the metal is usually carried out at temperatures below room temperature (-33ºC). Interaction A4 with aromatic bicyclic ring system A5, suitably protected, if appropriate, can be carried out in a wide temperature range, including room temperature and a more elevated temperature, 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 base and a mixture Acorda X represents oxygen or sulfur, protective groups are not used. Suitable solvents include, but are not limited to, DMF, CH3CN, acetone and a mixture of them. When X represents NR5where R5is a suitable silicon-containing protective group such as SEM (trimethylsilylethynyl), removing silicon-containing protective groups in NR5can be carried out using conditions well known to the experts in this area (Greene et. al., cited above). Typical reaction conditions include, but are not limited to, the use of tetrabutylammonium fluoride (TBAF) in suitable solvents such as THF, at elevated temperatures.

Scheme B

With regard to scheme B, commercially available 4-benzyloxyphenol A1 alkylate dihalogenoalkane, preferably dibromononane, such as 1,2-dibromoethane and 1,3-dibromopropane, B1, each of which is commercially available in a wide range of temperatures, while the preferred elevated temperature (Zhou, Z.-L. et al., J. Med. Chem. 1999, 42:2993-3000). The reaction is carried out in the presence of an inorganic base used, as is known, to facilitate the flow O-alkylation, such as, but not limited to, K2CO3Cs2CO3and a mixture of them. Suitable solvents include, but are not limited to, CH3CN and DMF is. Connection structure B2 is treated with amines B3 or in the presence or in the absence of a suitable amine base as described above, in a wide temperature range, with the preferred elevated temperature. Suitable solvents include CH3CN, CH2Cl2and DMF. Further transformation of the products obtained patterns A3 in the connection structure A6 described above for scheme A.

Scheme C

As for the schema, benzyl group of compounds of structure B2 can be removed using conditions of catalytic hydrogenation, is well known to specialists in this area (Greene et al., cited above). Suitable catalysts include, but are not limited to, Pd/C in solvents such as THF and a mixture of THF/ethanol. Such reactions typically occur at room temperature. Removing the benzyl group by B2 may be performed multiple-choice exercise using hydrogenation conditions with hydrogen transport, suitable solvents and temperature. Compounds of General structure C1 is treated with amines of structure B3 or in the presence or in the absence of a suitable amine base as described above, in a wide temperature range, with the preferred elevated temperature. Suitable solvents include, but are not limiting who they are, CH3CN, CH2Cl2and DMF. Further transformation of the received products A4 in connection A6 in detail above for scheme A.

Scheme D

With regard to 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, in a wide temperature range, with the preferred elevated temperature. Suitable solvents include, but are not limited to, DMF, CH3CN and a mixture of them. The conversion of compounds of structure D1 connection structure A6 can be carried out by treatment of compounds of structure B3. Such reactions can be performed in the presence or in the absence of a suitable amine base, as defined above, or inorganic bases, such as, but not limited to, K2CO3Cs2CO3and mixtures thereof, as described above, in a wide temperature range, thus are preferred elevated temperature. Suitable solvents include, but are not limited to, CH3CN and DMF.

It is assumed that when X represents NR5where R5represents a silicon-containing protective group, the synthesis must follow the synthesis, op the sled above. Furthermore, it was assumed that the removal of silicon-containing protective group at the end of the synthetic sequence takes place in conditions that are described in publications, such as (Greene et. al., cited above).

Scheme E

With regard to scheme E, treatment of compounds of structure E1 aromatic bicyclic compounds A5, where X is S, in the presence of a suitable inorganic bases, defined above, is carried out in a wide temperature range, with elevated temperatures preferred. Suitable solvents include, but are not limited to, DMF, CH3CN, and mixtures thereof. Connection structure of E2 can be converted into compounds of structure E3, using typical conditions, synthesized, including, but not limited to, the use of PBr3at elevated temperatures. Suitable solvents include, but are not limited to, benzene. Connection structure of E2 can be converted into compounds of structure E4, using conventional conditions sulfonylamine, well known to specialists in this field. These conditions include, but are not limited to, the use of TsCl and obtaining the tozilaty, as indicated in the Diagram, in the presence of an amine base at room temperature in CH2Cl2. The conversion of compounds of structure 3 in which soedineniya E5 can be carried out by treatment of compounds of structure B3. Such reactions can be performed either in the presence or in the absence of a suitable amine base, described above, or inorganic bases, such as, but not limited to, K2CO3Cs2CO3and mixtures thereof, in a wide temperature range, with the preferred elevated temperature. Suitable solvents include, but are not limited to, CH3CN and DMF. Connection patterns E4 can be converted into compounds of structure E5 treatment with compounds of structure B3. Such reactions can be performed in the presence or in the absence of a suitable amine base as described above, in a wide temperature range. Suitable solvents include, but are not limited to, CH3CN and DMF.

It is assumed that when X represents NR5where R5represents a silicon-containing protective group, the synthesis must follow the synthesis described above. In addition, it is envisaged that the removal of the silicon-containing protective group at the end of the synthetic sequence proceeds according to the conditions described in publications such as Greene et. al. (cited above).

Scheme F

With regard to scheme F, commercially available 4-(2-hydroxyethyl)phenol and 4-(2-hydroxypropyl)phenol is converted into the corresponding Ala halogenide F1, where HAL represents a chloride or bromide, using typical conditions of synthesized or chlorination. These conditions include, but are not limited to, treatment with 48% HBr solutions at elevated temperatures. The resulting Bromphenol patterns F1 can then be processed amines patterns B3 or in the presence or in the absence of a suitable amine base as described above, in a wide temperature range. Suitable solvents include, but are not limited to, CH3CN and DMF. The interaction of F2 with aromatic bicyclic ring system A5, protected in a suitable manner, if appropriate, can be carried out within a wide temperature range, including room temperature and a more elevated temperature, in the presence of a suitable amine or inorganic bases defined above. Suitable solvents include, but are not limited to, DMF, CH3CN, acetone and mixtures thereof. In those cases when X represents O or S, the protective group can not be used. When X represents NR5where R5is a suitable silicon-containing protective group such as SEM (trimethylsilylethynyl), removing silicon-containing protective groups in NR5can be performed using conditions well-known to specialists in this area (Greene et. al., city is consistent 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

With regard to scheme G, the connection G1, where n is 0 or 2 and HAL represents a bromide or chloride, is commercially available or can be obtained from *║*; and connection G1, where n is equal to 1 is assumed to be available, using standard alkylation conditions on the basis of 4-(2-hydroxyethyl)phenol and benzylchloride. Benzyl group G1 is used as a protective group. In this sequence can be used and other compatible protective groups known to the person skilled in the art. Compounds having the General structure G2, can be obtained by treatment of amines of the General structure B3 or in the presence or in the absence of a suitable amine base as described above, in a wide temperature range. Suitable solvents include, but are not limited to, CH3CN and DMF. The removal of the benzyl group can be carried out using conditions of catalytic hydrogenation, well-known specialists in this field (Greene et. al., cited above). Suitable catalysts include, but are not limited to, Pd/C in solvents such as ethyl acetate, alcohols, and mixtures thereof. Examples of the alcohols in luchot, but not limited to, CH3OH, ethanol, i-D. Such reactions typically occur at room temperature. Removal of benzyl group G2 can be performed using several embodiments, for example using the conditions of hydrogenation with hydrogen transport at appropriate temperatures. Further transformation of the products obtained F2 in the final target compound F3 in detail above for scheme F.

Scheme H

With regard to scheme H, commercially available 4-benzyloxyphenol A1 is treated with epichlorohydrin H1, both of which are commercially available. The reaction can be carried out in a wide temperature range, with the preferred elevated temperature, in the presence of inorganic bases, such as, but not limited to, K2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, DMF. The conversion of compounds of structure H2 in the connection structure of H3 can be carried out by treatment of amines of the General structure B3 or in the presence or in the absence of a suitable amine base, described above, or inorganic bases, such as, but not limited to, K2CO3Cs2CO3and mixtures thereof, in a wide temperature range, with the preferred elevated temperature is URS. Suitable solvents include, but are not limited to, CH3CN and DMF. Removal of benzyl groups on H3 can be performed using the conditions of catalytic hydrogenation, well-known specialists in this field (Greene et. al., cited 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, CH3OH, i-D. Such reactions typically occur at room temperature. Removing the benzyl group by B2 may be done in several variants, using hydrogenation conditions with hydrogen transport, suitable solvents and temperature. The conversion of compounds of structure H4 ultimately required connections H5 can be accomplished by treatment of aromatic bicyclic ring system A5, where X is Oh, in the presence of a suitable inorganic bases defined above, in a wide temperature range, with the preferred elevated temperature. Suitable solvents include, but are not limited to, acetone.

It is assumed that when X represents NR5where R5represents a silicon-containing protective group, the synthesis must follow the synthesis described above. In addition, it is envisaged, toadlena silicon-containing protective group at the end of the synthetic sequence proceeds using conditions, described in publications such as Greene et. al. (cited above).

Scheme I

With regard to scheme I, compounds of type I5 obtained by heating commercially available 4-hydroxyphenylarsonic acid with 2-aminothiophenol in the case when X is S. In the case when X represents O, use 2-aminophenol. Two of the original product is heated in the absence of solvent and the resulting phenols I3 process dihalogenoalkane, preferably dibromononane, such as 1,2-dibromoethane and 1,3-dibromopropan B1, both of which are commercially available in a wide range of temperatures, while the preferred elevated temperature (Zhou, Z.-L. et al., cited above). The reaction is carried out in the presence of an inorganic base used, as is known to facilitate the flow O-alkylation, such as, but not limited to, K2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, CH3CN and DMF. Connection structure I4 is treated with amines B3 or in the presence or in the absence of a suitable amine base as described above, in a wide temperature range, with the preferred elevated temperature. Suitable solvents include CH3CN, CH2Cl2and DMF.

Scheme J

With regard to scheme J, the connection patterns J1 can be further converted, without limiting the claims to more vyisokofunktsionalnyih target compounds. For example, hydrolysis using methods well-known to specialists in this field, such as the use of aqueous solutions of LiOH, KOH or NaOH, or aqueous solutions of HCl or CH3CO2H, or the use of (CH3)3SiOK. In addition, professionals in this field will be obvious that some compounds are more suitable to obtain according to one method than another, and that the initial result may be obtaining salts of the desired compounds. Compounds of structure J2 can then be modified to obtain amides, using well-known to experts in the field of methods, including, but not limited to, the use of (COCl2)2for conversion into an intermediate product, the acid chloride of the acid, with subsequent exposure to amines of structure B3. Alternatively can be used the usual conditions for the formation of amide linkages, including, but not limited to, the use of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI) with or without additives such as HOBT, and amines of structure B3. Connection patterns J4 can be further subjected to transformation by g is dreamindemon, using conventional conditions known to the experts in this field, including, but not limited to, the use of amine structure B3 and NaBH(OAc)3in an appropriate solvent such as CH2Cl2, ClCH2CH2Cl or CF3CH2OH.

Scheme K

With regard to scheme K, commercially available 3-fluoro-4-oxybenzoic acid K11 is converted into amides K2 with amines of structure B3, using conventional conditions binding peptides are well known to specialists in this field, such as, but not limited to, the use of the hydrochloride of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 1,3-dicyclohexylcarbodiimide (DCC), hexaflurophosphate O-(7-asobancaria-1-yl)-N,N,N',N'-tetramethylurea (HATU), O hexaphosphate-benzotriazol-1-N,N,N',N'-tetramethyluronium (HBTU) and mixtures thereof. Suitable solvents include, but are not limited to, CH2Cl2and THF. Received amides patterns K2 restore in amines of formula K3 in terms of recovery, is well known to specialists in this field, including, but not limited to, sociallyengaged in an appropriate solvent, such as, but not limited to, THF. Convert benzylamino K3 in the final target compound K4 can be carried out by treatment of aromatic bicyclic compound A5, where X is predstavljaet a S or O, in the presence of a suitable inorganic base in a wide range of temperatures, preferably elevated temperatures. Suitable inorganic bases include, but are not limited to, K2CO3Cs2CO3and mixtures thereof. Suitable solvents include, but are not limited to, acetone, and CH3CN.

It is assumed that when X represents NR5where R5represents a silicon-containing protective group, the synthesis must follow the synthesis described above. In addition, it is envisaged that the removal of the silicon-containing protective group at the end of the synthetic sequence proceeds according to the conditions described in publications such as Greene et. al. (cited above).

Scheme L

With regard to scheme L, it is a description of an alternative of obtaining compounds of formula (I), where n is 0. The original product L1, 4-oxybenzaldehyde, is converted into ethers of the formula L2 processing of aromatic bicyclic ring system A5, where X is S or O, in the presence of a suitable inorganic base in a wide range of temperatures, preferably elevated temperatures. Suitable inorganic bases include, but are not limited to, K2CO3Cs2CO and a mixture of them. Suitable solvents include, but are not limited to, acetone, and CH3CN. It is assumed that when X represents NR5where R5represents a silicon-containing protective group, the synthesis must follow the synthesis described above. In addition, it is envisaged that the removal of the silicon-containing protective group at the end of the synthetic sequence proceeds according to the conditions described in publications such as Greene et. al. (cited above). The aldehydes of the formula L2 is converted into amines of the formula L3 in terms gidroaminirovaniya with amines of formula B3. Suitable reducing agents include Na(OAc)3BH and NaCNBH3with or without the addition of an activating means, such as acetic acid or ZnCl2. Suitable solvents include THF and methanol, and the reaction temperature can vary from 0ºC to 70ºC. The preferred reaction conditions are Na(OAc)3BH in THF at room temperature.

Pharmaceutically acceptable salts, esters and amides of the compounds according to the invention relate to the forms of salts of ester and amide compounds according to this invention, which should be obvious to a pharmacist / chemist, i.e. those which are non-toxic and which may favorably affect the pharmacokinetic characteristics of the compounds shown in this invention. Such compounds with favorable pharmacokinetic properties, will be obvious to a pharmacist / chemist, i.e. are compounds that are non-toxic and which have pharmacokinetic properties that can provide sufficient palatability (nice flavor), absorption (absorption, distribution, metabolism and excretion. Other factors, more practical in nature, which are also important when choosing include the cost of the starting substances, ease of crystallization, yield, stability, hygroscopicity and fluidity of the obtained bulk drugs.

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

A wider range of examples of acids and bases that can be used to obtain pharmaceutically acceptable salts, include the following: acids, such as acetic acid, 2,2-dichloracetic acid, acylated and is inability, 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, reklamowa acid, modellerna acid, ethane-1,2-disulfonate acid, econsultancy acid, 2-hydroxyethanesulfonic acid, formic acid, fumaric acid, galactosemia acid, gentisic acid, glucoheptonate acid D-gluconic acid, D-glucuronic acid, L-glutamic acid, b-oxo-glutaric 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, p is Aranova 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)pyrrolidine, 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, the contents of which are incorporated into this description by reference.

Examples of suitable esters include esters, where 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,

adamantios what icarbonell, 2-benzyloxycarbonyl,

4-methyltrioctylammonium or

tetrahydropyran-2-rockstarvania.

Compounds according to this invention can be used in pharmaceutical compositions to treat patients (humans and other mammals) with disorders associated with the activity of LTA4H enzyme. In particular, the compounds of this invention can be used in pharmaceutical compositions for treatment of inflammation. More specifically the compounds of this invention can be used in pharmaceutical compositions for treatment of inflammatory conditions such as inflammatory bowel disease (IBD) (for example, Crohn's disease - regional enteritis and ulcerative colitis), chronic obstructive pulmonary disease (COPD), arthritis, psoriasis, asthma, cystic fibrosis, atherosclerosis, rheumatoid arthritis and multiple [multiple] sclerosis.

The present invention provides pharmaceutical compositions containing the above compounds and methods of using such compositions for the treatment or prevention of conditions which are mediated by LTA4H enzyme activity. Accordingly, the present invention also considers a pharmaceutical composition, which contains at least one compound according to this invention, preferably dispersed in the headlights is asepticheski acceptable carrier. In this composition there is at least one compound according to this invention in an amount sufficient for inhibiting the activity of LTA4H enzyme. In particular, such a composition is at least one compound according to this invention in an amount necessary to eliminate the inflammation.

Accordingly also provides a pharmaceutical composition that includes an anti-inflammatory amount of at least one compound according to this invention in a pharmaceutically acceptable carrier. The composition comprises a unit dose of at least one compound according to this invention. In preferred practice, when such pharmaceutical composition is administered in a single dose corresponding to a patient or subject, at least one which is included as part of the connection according to this invention are able to inhibit the activity of LTA4H enzyme in the quantities in which the specified connection is present in the pharmaceutical composition.

As used in this description, the term "single dose" and their grammatical equivalent form refers to physically discrete units suitable as uniform doses to humans and other animals, each unit contains a preset effective pharmacological STA is in active component, ensure accordance with the calculation of the desired pharmacological effect. Specifications for the new unit dosage forms are determined by and directly dependent on the properties of the active component from the limitations inherent in the field of compounding such an active ingredient for therapeutic use of people and other animals.

The pharmaceutical compositions can be obtained using conventional pharmaceutical excipients and methods of compounding. Examples of suitable unit dosage forms are tablets, capsules, pills, sachets of powder, granules, wafers, etc., separate set any unit dosage forms, as well as liquid solutions or suspensions. Oral dosage forms can be represented as elixirs, syrups, capsules, tablets, etc. are Examples of solid carriers include substances generally used to get the pills or tablets, such as lactose, starch, glucose, methylcellulose, magnesium stearate, dicalcium phosphate, mannitol and the like, thickeners, such as tragakant and methylcellulose USP, thinly dispersively SiO2, polyvinylpyrrolidone, magnesium stearate and the like Typical oral liquid excipients include ethanol, glycerol, water, etc. All excipients can be mixed, as required, with inert diluents (e.g., the carbonates, the rija and calcium, phosphates of sodium and calcium and lactose), disintegrants (for example, corn starch and alginic acid), diluents, granulating agents, lubricants (e.g. magnesium stearate, stearic acid and talc), binders (such as starch and gelatin), thickeners (for example, paraffin, waxes and petrolatum, fragrances, dyes, preservatives and the like, conventional methods known to experts in the field of preparation of dosage forms. Can also be used for the coating, and to substances, components, include, for example, glycerylmonostearate and/or glycerylmonostearate. Capsules for oral use 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 or oil, such as peanut oil, liquid paraffin or olive oil.

Parenteral dosage forms can be obtained by using water or other sterile media. For intramuscular, intraperitoneal, subcutaneous and intravenous administration of the compounds of this invention are normally provided in sterile aqueous solutions or suspensions, buffered to an appropriate pH and isotonicity. Suitable water fillers include ringer's solution and isotonic the ski sodium chloride. Aqueous suspensions may include suspendiruemye tools, such as derivatives of cellulose, sodium alginate, polyvinylpyrrolidone and tragacanth gum, and humectants, such as lecithin. Suitable preservatives for aqueous suspensions include ethyl and n - propyl-p-hydroxybenzoate.

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

The pharmaceutical compositions according to the present invention may contain suitable emulsifying means commonly used in the emulsion compositions. Such emulsifiers are described in regular publications, such as H.P. Fiedler, 1989, Lexikon der Hilfsstoffe fur Pharmazie, Kosmetic und agrenzende Gebiete, Cantor ed., Aulendorf, Germany, and in the Handbook of Pharmaceutical Excipients, 1986, American Pharmaceutical Association, Washington, DC, and the Pharmaceutical Society of Great Britain, London, UK, the contents of which are incorporated into this description by reference. The compositions of this invention can be also added to the gel-forming means. Derivatives of polyacrylic acid, such as carbomer, are examples of gel-forming means and, often the spine, different types of carbopol, which are usually used in amounts from about 0.2% to about 2%. Suspension can be obtained in the form of creams, ointments, including anhydrous ointment, emulsion, water-in-oil emulsion, oil-in-water, emulsion, gel or gel.

It is expected that the compounds according to this invention can be administered orally or parenteral routes, including intravenous, intramuscular, intraperitoneal, subcutaneous, rectal and local injection, by inhalation. For oral administration the compounds according to this invention are normally provided in the form of tablets, capsules or in the form of a solution or suspension.

"Therapeutically effective amount" or "effective amount" and grammatically related terms means the amount of active compound or pharmaceutical agent that causes a biological or medicinal response that is being hunted by a researcher, veterinarian, doctor or other Clinician, and this response includes the relief of symptoms of the disease or disorder being treated. The term "subject" or "patient" includes mammals, such as humans and animals (e.g. dogs, cats, horses, rats, rabbits, mice, non-human primates), in need of supervision, experiment, treatment or prevention in connection with the relevant disease or is a being. Preferably, the patient or subject is a human.

Effective doses of the compounds according to this invention can be installed by conventional methods. The specific dose required for any particular patient, usually depends on a number of factors, including the severity of the condition, the route of administration and body weight of the patient.

In General, it is assumed that the daily dose (regardless of whether you enter it as a single dose or as divided doses) will be in the range from about 0.01 mg to about 1000 mg per day, more usually from about 1 mg to about 500 mg per day, and most typically from about 10 mg to about 200 mg per day. Expressed as dose per unit of body weight of a typical dose would be expected to be from about 0,0001 mg/kg to about 15 mg/kg, preferably from about 0.01 mg/kg to about 7 mg/kg and most preferably from about 0.15 mg/kg to 2.5 mg/kg

Estimated oral dose ranges include from about 0.01 to 500 mg/kg per day, more preferably from about 0.05 to about 100 mg/kg, administered at 1-4 separate doses. Some compounds in this invention can be administered orally in doses ranging from about 0.05 to about 50 mg/kg per day, while the other (compound) can be administered in doses of from 0.05 to about 20 mg/kg per day. Dose infusion may range from about 1.0 to about 1.0×104ág/(kg·m is n) inhibitor, mixed with a pharmaceutical carrier over a period of time, from several minutes to several days. In the case of topical application of the compounds according to this invention can be mixed with a pharmaceutical carrier at a concentration from about 0.1 to about 10% of the medicines in relation to the media.

It also covers a method of treating inflammation in a patient, demonstrating or susceptible to an inflammatory state. Also considered a method of treatment of LTA4H-mediated condition. The methods include the administration to the patient an effective amount of a pharmaceutical composition, which comprises a unit dose of the active component, i.e. at least one of the compounds according to this invention, dispersed in a pharmaceutically acceptable carrier.

To provide a more concise narrative descriptions of some of the quantitative expressions presented in it, are not stipulated by the term “about”. Have in mind that regardless of whether you use the term "about" or not, it is assumed that each as defined in the present description the number refers to the actual set value, and assume that this is related to the approximation of such a specific value that can reasonably be typed using the correct skill level specifications the sheet in this area, including approximation, due to the conditions of the experiment and/or conditions of the measurement of the specified set value. Whenever is output in the form of a percentage, this output refers to the mass of the substance for which the output is given relative to the maximum quantity of the same substance, which can be obtained in specific stoichiometric conditions. Concentrations, which are in the form of interest related to mass relationship, if not specified.

EXAMPLES

For illustration of this invention included the following examples. These examples do not limit the invention. They are, as implied, only confirm the method of implementation in practice of the present invention. Specialists in this field can find other ways of implementing the present invention, which are obvious. However, it is believed that such methods are included in the scope of this invention.

General experimental methods of analysis:

NMR spectra were obtained on a spectrometer Bruker model DPX400 (400 MHz) or DPX500 (500 MHz). Format1H-NMR: chemical shift, expressed in ppm, in the weak field from the signal of the internal standard tetramethylsilane (multipletness; the interaction constant J, expressed in Hz, integrated is (e).

Mass spectra were obtained on a mass spectrometer Agilent MSD 1100 operating mode electrospray ionization (ESI) with the registration either positive or negative ions, as indicated. "The calculated mass for the molecular formula is a monoisotopic mass of connections.

The retention time of the component in the case of HPLC with reversed phase represented in minutes, the following are the conditions and methods of analysis.

Instrument:Gilson 215
Solvent:CH3CN (0.05% of triperoxonane acid, TFA)/H2About (0.05% of TFA)
Flow rate:25 ml/min
Gradient:0 min 10% CH3CN; 20-min linear increase to 99% of CH3CN;
Column:YMC-Pack ODS-A AA 12505-1530WT SH-362-5 (S-5 μm, 12 nm, 150×30 mm)
Temperature:25ºC
Wavelength:Dual detection at 220 and 254 nm

Column flash chromatography was carried out using the system ISCO Foxy 200 or ISCO OPTIX 10X, using one of the following to mirceski available predalone (printed precolumn filters): Biotage 40S (SiO 240 g), Biotage 40M (SiO290 g), Biotage 40L (SiO2120 g), Biotage 65M (SiO2300 g) or ISCO Redisep (SiO2, 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 CH3CN (600 ml) add dibromethane (155 ml of 1.80 mol) and K2CO3(105 g, 759,9 mmol). The brown suspension is heated at boiling temperature under reflux and allow to mix for 96 hours, the resulting suspension is cooled to room temperature, diluted with acetone (250 ml) and filtered through a layer of diatomaceous earth, which is then washed with additional acetone. The filtrate is concentrated under reduced pressure. The resulting oil was dissolved in CH3OH (500 ml) and the solution stirred for 2 hours Specified in the title compound is obtained by filtration and air-dried, obtaining 70 g (228 mmol, 63% yield) as a yellowish brown solid.

1H NMR (400 MHz, CDCl3): 7,60-7,30 (m, 5H), to 6.88 (d, J=8,4, 2H), 6,80 (d, J=8,4, 2H), 4,70 (c, 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 CH3CN (125 ml) add dibromopropan (63 ml, 624 mmol) and K2CO3(34,5 g, 250 the mol). The brown suspension is heated at the boil under reflux and allow to mix for 66 hours and Then the suspension is cooled to room temperature and filtered twice through a layer of diatomaceous earth. Layer was washed with CH3CN and the combined filtrates concentrated under reduced pressure. The resulting oil purified on SiO2(300 g; a mixture of 33% CH3Cl2/hexane), receiving of 35.4 g (110 mmol, yield 88%) of a brown solid.

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), 5,03 (c, 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-Bromoethoxy)phenol

2-(4-Benzyloxyphenyl)ethylbromide (example 1; 70 g, 227 mmol) dissolved in THF (THF) (500 ml). To the resulting solution was added Pd on carbon (10 wt.%, 7 g) in suspension in ethanol (50 ml). The resulting suspension is placed in hydrogenator Parra at a pressure of H240 lb/in2and subjected to shaking during the night. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, getting to 48.5 g (224 mmol, yield 99%) of a yellowish brown solid.

1H NMR (400 MHz, CDCl3): 6,83 (d, J=9,1, 2H), 6,77 (d, J=9,1, 2H), 4,51 (c, 1H), 4,24 (t, J=6,3, 2H), 3,62 (t, J=6,3, 2H).

EXAMPLE 4

4-(3-Bromopropane)phenol

240 lb/in2and subjected to shaking during the night. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, obtaining 7 g (30,5 mmol, yield 98%) of a yellowish brown solid.

1H NMR: (400 MHz, CDCl3): 6,76 (d, 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 to (m, J=6,1, 2H).

EXAMPLE 5

4-(2-Bromacil)phenol

4-(2-Hydroxyethyl)phenol (50 g, 362 mmol) is dissolved in 48 wt.% HBr (250 ml). The obtained pale-yellow solution is heated to 80ºC and stirred for 16 hours the Reaction mixture allow to cool to room temperature and then extracted with CH2Cl2(3×50 ml). The combined extracts dried, filtered and concentrated under reduced pressure, receiving 72 g (crude yield 100%) of a yellowish brown solid.

1H NMR (400 MHz, CDCl3): 9,25 (c, 1H), 7:04 (d, J=8,4, 2H), to 6.67 (d, 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 80ºC for 20 h and is then cooled to room temperature. Add water (400 ml) and the product extracted with CH2Cl2(500 ml). The extract is dried (MgSO4) and concentrated under reduced pressure, obtaining the desired product as a beige solid (69 g, yield 92%). TLC (SiO2CH2Cl2): Rf=0,37.

1H NMR (400 MHz, DMSO-d6): 9,18 (c, 1H), 6,99 (d, J=8,3, 2H), to 6.67 (d, 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-benzimidazole

To a suspension of sodium hydride (6.2 g, 245 mmol) in DMF (275 ml) at 5°C is added through a funnel to add solids 2-chlorobenzimidazole (37 g, 243 mmol) over 30 min while maintaining the internal temperature of the mixture below 10ºC. Add an additional 25 ml of DMF and bath with ice removed. After 2 h added dropwise 2-(trimethylsilyl)ethoxymethylene (SEM-Cl) for 5 minutes a white precipitate is Formed. The reaction mixture was stirred at room temperature for 18 hours To the mixture of H2O (500 ml) and ethyl acetate (750 ml). The organic layer was washed with an additional quantity of H2O (500 ml), dried (MgSO4) and concentrated under reduced pressure, getting 65.8 g (yield 96%) of the desired product in the form of a clear Golden oil, which solidifies upon standing, giving a beige solid. TLC (SiO2with 5% acetone/CH2Cl2R f=0,64. MS (ESI): mass calculated for C13H19ClN2OSi, 282,10; found m/z 283,1.

1H NMR (400 MHz, CDCl3): of 7.70 (d, J=7,3, 1H), 7,46 (d, J=7,6, 1H), 7,40-7,25 (m, 2H), to 3.58 (t, J=7,9, 2H), to 0.92 (t, J=8,3, 2H), 0,04 (c, 9H).

EXAMPLE 8

2-Chloro-1-methyl-1H-benzimidazole

Dimethylsulfate (11,0 ml, 116 mmol) are added to a solution of 2-chlorobenzimidazole (10.6 g, 70 mmol) in 2,5M NaOH (70 ml, 175 mmol) and the mixture is stirred at 23º C for 2 h, the Reaction mixture was filtered, the solid product is washed with N2About (6×50 ml) and dried in vacuum, obtaining a light brown solid (9.4 g, yield 81%). MS (ESI): mass calculated for C8H7ClN2, 166,03; found m/z 167,0 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,75-of 7.70 (m, 1H), 7,35-7,29 (m, 3H), 3,82 (c, 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 CH3CN is treated with finely powdered Cs2CO3(26 g, 80 mmol) and the resulting mixture was stirred at 23ºC for 30 hours, the Reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure. The crude solid is purified on SiO2(100 g; 0-40% ethyl acetate/hexane)to give 6.7 g (yield 47%) of white solids. MS (ESI): mass calculated DL is 15H12BrNO2S 348,98; found m/z 350,0 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,78, (DD, J=8.0 a, 0,4, 1H), of 7.70 (DD, J=8.0 a, 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-chlorobenzothiazole of 0.82 ml, 6.3 mmol) in CH3CN is treated with finely powdered Cs2CO3(4.1 g, 12.5 mmol) and the resulting suspension is stirred for 40 h at 70ºC. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated to a crude oil which was purified on SiO2(40 g; 0-50% ethyl acetate/hexane)to give 940 mg (yield 55%) of a clear oil. MS (ESI): mass calculated for C15H13NO2S, 271,07; found m/z 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).

B.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) is treated PBr3(to 0.060 ml, 0.64 mmol) and the resulting suspension heated to 70ºC for 90 minutes the Reaction mixture is cooled and diluted with ethyl acetate (30 ml). The resulting solution was washed with H2On (10ml), then a saturated solution of salt (10 ml), dried and concentrated under reduced pressure. The crude product is purified on SiO2(12 g; 0-50% ethyl acetate/hexane), receiving 120 mg of light yellow oil. MS (ESI): mass calculated for C15H12BrNOS, 332,98; found m/z 335,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,79 (DD, J=8.0 a, 0,3, 1H), 7,76 (DD, J=8.0 a, 0,6, 1H), 7,42 (dt, J=7,4, 1,2, 1H), 7,38-7,29 (m, 3H), 3,62 (t, J=7,5, 2H), 3,25 (t, J=7,5, 2H).

EXAMPLE 11

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

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) add K2CO3(25 g, 181 mmol) and CS2CO3(40 g, 123 mmol). The reaction mixture is stirred for 3 days at room temperature. To this mixture N2O (300 ml) and CH2Cl2. The organic layer is washed with 10% NaOH, then with a saturated solution of salt, dried (MgSO4), filtered and concentrated under reduced pressure, obtaining 33 g transparent dark purple liquid. The resulting liquid is purified on SiO2(300 g; 0-50% ethyl acetate/hexane), receiving of 23.4 g (yield 67%) of light yellow solid. TLC (SiO250% of hexane/ethyl acetate): Rf=0,11. MS (ESI): mass calculated for C20H25NO2, 311,19; found m/z 312,2 [M+H]+.

1 H NMR (400 MHz, CDCl3): 7,50-7,26 (m, 5H), 6,91 (d, J=9,2, 2H), 6,85 (d, J=9,2, 2H), 5,02 (c, 2H), 4,06 (t, J=6,1, 2H), was 2.76 (t, J=6,1, 2H), of 2.51 (users, 4H), 1,65-of 1.55 (m, 4H), 1,45 (users, 2H).

B.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 1:1 ethanol/ethyl acetate (400 ml) is added Pd on carbon (10 wt.%, 1.5 g). The mixture is placed in hydrogenator Parra at a pressure of H240 lb/in2and hydronaut for 20 hours, the Reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, obtaining 9.4 g (yield 88%) of the desired product as a light grey solid. TLC (SiO2, 50% acetone/CH2Cl2): Rf=0,16. MS (ESI): mass calculated for C13H19NO2, 221,14; found m/z 222,1 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,88 (c, 1H), 6.73 x (d, J=6,6, 2H), 6,65 (d, J=6,6, 2H), 3,93 (t, J=6,0, 2H), 2,58 (t, J=6,0, 2H), 2.40 a (c, 4H), 1,51-of 1.45 (m, 4H), 1,35 (users, 2H).

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

To a stirred solution of 4-(2-piperidine-1-ylethoxy)phenol (1.5 g, 6.8 mmol) in acetone (20 ml) at 5ºC add K2CO3(1.0 g, 7.2 mmol). To this mixture 2-chlorobenzoxazole (0.5 ml, 4.4 mmol) at 5ºC. The resulting mixture was warmed to room temperature over night. After 20 h the mixture is filtered and the filtrate concentrated under reduced pressure, obtaining a brown solid, which is AutoRAE purified on SiO 2(35 g; 50% acetone/CH2Cl2). The desired fractions are combined and concentrated under reduced pressure, obtaining 1.2 g (yield 80%) of the desired product as a white solid. TLC (SiO2, 50% acetone/CH2Cl2): Rf=0,18. MS (ESI): mass calculated for C20H22N2O3, 338,16; found m/z 339,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,52 (d, J=7,2, 1H), 7,41 (d, J=7,2, 1H), 7,35-7,20 (m, 4H), 6,97 (d, J=9,1, 2H), 4,12 (t, J=6,1, 2H), and 2.79 (t, J=6,0, 2H), 2,52 (c, 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) add K2CO3(37 g, 268 mmol) and Cs2CO3(87 g, 267 mmol). The reaction mixture was stirred at room temperature for 17 days. To the mixture add H2O (600 ml) and CH2Cl2. The organic layer was washed with H2Oh, dried (MgSO4), filtered and concentrated under reduced pressure, obtaining 33 g transparent dark purple liquid, which is purified on SiO2(300 g; ethyl acetate)to give light yellow oil (34,5 g, yield 48%). TLC (SiO250% of hexane/ethyl acetate): Rf=0,10. MS (ESI): mass calculated for C19H25NO2, 299,19; found m/z to 300.2[M+H] +.

1H NMR (400 MHz, CDCl3): 7,50-7,28 (m, 5H), 6.89 in (d, J=9,2, 2H), 6,85 (d, J=9,2, 2H), 5,02 (c, 2H), 4.00 points (t, J=6,4, 2H), 2,86 (t, J=6,4, 2H), 2.63 in (kV, J=7,2, 4H), of 1.08 (t, J=7,1, 6H).

B.4-(2-Diethylaminoethoxy)phenol

To a solution of [2-(4-benzyloxyphenyl)ethyl]diethylamine (21 g, 70 mmol) in a mixture of 1:1 ethanol/ethyl acetate (500 ml) is added Pd on carbon (10 wt.% 1.5 g). The mixture is placed in hydrogenator Parra at a pressure of H240 lb/in2and hydronaut for 20 hours, the Reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, obtaining of 13.1 g (yield 89%) of the desired product as a clear brown oil. MS (ESI): mass calculated for

With12H19NO2, 209,14; found m/z 210,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 6,68 (c, 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}diethylamin

To a solution of 4-(2-diethylaminoethoxy)phenol (500 mg, 2,39 mmol) in acetone (7 ml)containing Cs2CO3(876 mg, 2,69 mmol), added 2,6-dichlorobenzothiazole (365 mg, to 1.79 mmol). The mixture is heated at the boil under reflux for 3 days. The reaction mixture is filtered and the filtrate concentrated under reduced pressure, obtaining a brown oil which is purified on SiO2(35 g; acetone)to give 624 mg (yield 76%) of the desired product. TLC (SiO2, acetone): Rf=0,23 MS (ESI): mass, calculated for C19H21ClN2O2S, 376,10; found m/z 377,1 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.64 (d, J=8,5, 2H), 7,34 (d, J=8,8, 1H), 7,25 (d, J=6,8, 2H), of 6.96 (d, J=9,1, 2H).

EXAMPLE 13

(1-{2-[4-(Benzoxazol-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 CH3CN (100 ml) was stirred at 65 º C for 18 hours the Reaction mixture is cooled to room temperature and stirred for further 48 hours the Solvent is removed under reduced pressure, obtaining a brown semi-solid substance. The resulting material was dissolved in CH2Cl2(200 ml) and the solution washed with H2About (2×50 ml). The aqueous phase is again extracted with a mixture of 10% CH3OH/CH2Cl2(100 ml). The organic layers are combined, dried (Na2SO4), filtered and concentrated under reduced pressure, obtaining a black oil, which was purified on SiO2(120 g; 0-100% acetone/CH2Cl2)to give the desired product as a brown oil. To the oil is added diethyl ether to precipitate the product. Filtering network specified in the title compound as a yellowish brown solid (1.9 g, yield 23%). TLC (SiO2with 5% 2M NH3in CME and CH 3OH/CH2Cl2): Rf=0,09. MS (ESI): mass calculated for C14H21NO3, 251,15; found m/z 252,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 6,69 (c, 4H), a 4.03 (t, J=5,9, 2H), 3,51 (d, J=6,5, 2H), 3,09 (d, J=11,6, 2H), and 2.79 (t, J=5,9, 2H), 2,18-2,11 (m, 2H), 1,79 (d, J=16,2, 2H), 1,49-of 1.62 (m, 1H), 1,36 (l kV, J=3,6, 12,3, 2H), 1,23 (users, 2H).

B.(1-{2-[4-Benzoxazol-2-yloxy)phenoxy}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 is filtered through a layer of diatomaceous earth, washed with CH2Cl2. The combined filtrates are concentrated under reduced pressure, obtaining a yellow oil. The oil is purified on SiO2(40 g; 0-100% acetone/CH2Cl2), receiving solid, which was dissolved in CH2Cl2(100 ml). The resulting solution was washed with 1N. NaOH (3×5 ml), then N2O (5 ml), dried (Na2SO4), filtered and concentrated under reduced pressure, obtaining mentioned in the title compound as a white solid (424 mg, yield 64%). TLC (SiO2with 5% 2M NH3in a mixture of CH3HE/CH2Cl2): Rf=0,17. MS (ESI): mass calculated for C21H24N2O4, 368,17; found m/z 369,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,537,50 (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 (l kV, J=3,7, 12,4, 2H).

EXAMPLE 14

1-{2-[4-(Benzoxazol-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 CH3CN (150 ml) is added 4-hydroxypiperidine (5.3g, 52,5 mmol) followed by addition of N,N-diisopropylethylamine (6.7 g, is 52.5 mmol). The resulting solution is stirred over night at room temperature, obtaining a suspension. The suspension is filtered and the filtrate concentrated under reduced pressure. To the resulting oil is added diethyl ether and the mixture is heated to 45ºC for 2 min, obtaining a white precipitate. The resulting suspension is stirred at room temperature for 2 h, then filtered, obtaining 7.9 g (33 mmol, yield 79%) not quite white solid. MS (ESI): mass calculated for C13H19NO3, 237,14; found m/z 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).

B.1-{2-[4-(Benzoxazol-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) add Cs 2CO3(1.4 g, to 4.41 mmol). The resulting suspension is cooled to 0ºC and added dropwise 2-chlorobenzoxazole (388 mg, 2.5 mmol, 0,29 ml). The reaction mixture allow to warm to room temperature overnight, then filtered and concentrated under reduced pressure. The resulting oil purified on SiO2(40 g; 0-100% acetone/CH2Cl2)to give 400 mg (1.1 mmol, yield 54%) of white solids. MS (ESI): mass calculated for C20H22N2O4, 354,16; found m/z 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 (d, 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 (users, 1H), 1,99 (m, 2H), 1,74-of 1.65 (m, 2H), 1,48 (d, 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) add CS2CO3(1.4 g, to 4.41 mmol) and 2-chlorobenzothiazole (0.33 ml, 2.5 mmol). The suspension is heated to 80ºC and stirred over night. The reaction mixture allow to cool to room temperature and then filtered through a layer of diatomaceous earth. The filtrate is concentrated under reduced pressure and the residue purified on SiO2(40 g; 0-100% acetone/CH2Cl2), getting 321 mg (0.86 mmol, yield 69%) of yellowish-is it solid. MS (ESI): mass calculated for C20H22N2O3S, 370,14; found m/z 371,2 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.64 (d, J=8,0, 1H), 7,56 (d, J=7,8, 1H), 7,30 (t, J=7,2, 1H), 7,21-7,14 (m, 3H), 6.87 in (d, J=9,1, 2H), of 4.05 (t, J=5,8, 2H), 3,67 (users, 1H), 2,82 (m, 2H), was 2.76 (t, J=5,8, 2H), and 2.27 (t, J=9,5, 2H), 2,01 (users, 1H), 1,90-to 1.82 (m, 2H), 1,64-of 1.52 (m, 2H).

EXAMPLE 16

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

A.4-(2-Dibutylaminoethanol)phenol

To a stirred solution of 4-(2-bromoethoxy)phenol (example 3; 8,2 g, 37 mmol) in CH3CN (150 ml) add dibutylamine (5,98 g, and 46.3 mmol) and N,N-diisopropylethylamine (5,98 g, and 46.3 mmol). The mixture is stirred over night at 75ºC. The resulting suspension is filtered and the filtrate concentrated under reduced pressure. The resulting oil purified on SiO2(110 g; 0-100% acetone/CH2Cl2getting to 7.7 g (29 mmol, yield 78%) of a brown solid. MS (ESI): mass calculated for C16H27NO2, 265,2; found m/z 266,2 [M+H]+.

1H NMR (400 MHz, CDCl3): for 6.81 (d, J=7,0, 2H), 6,63 (d, J=6,0, 2H), 4,22 (users, 2H), 3,25 (users, 2H), 2,93 ,(users, 4H), 2,16 (users, 2H), 1,88 (users, 1H), 1,68 (users, 4H), of 1.33 (d, J=5,7, 4H), 0,94 (users, 6H).

B.{2-[4-(Benzoxazol-2-yloxy)phenoxy]ethyl}dibutylamine

To a stirred solution of 4-(2-dibutylaminoethanol)phenol (500 mg, 1.9 mmol) in acetone (9.4 ml) add Cs2CO3(1.3 g, 3.9 mmol). Obtained the spengiu cooled to 0ºC and added dropwise 2-chlorobenzoxazole (346 mg, 2.2 mmol, 0.26 per ml). The reaction mixture allow to warm to room temperature overnight, then filtered. The filtrate is concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and purified on SiO2(40 g; 0-100%

acetone/CH2Cl2)to give 180 mg (0.47 mmol, yield 25%) of a white solid. MS (ESI): mass calculated for C23H30N2O3, 382,23; found m/z 383,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50 (d, J=7,2, 2H), 7,41 (d, J=7,3, 2H), 7,31 (d, 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 of 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 CH3CN (200 ml) add utilizedabated (5,3 ml of 34.7 mmol). The reaction mixture is heated to 84ºC and stirred for 16 h, then cooled to room temperature and concentrate under reduced pressure. The resulting oil was dissolved in CH2Cl2and purified on SiO2(300 g; 0-25% acetone/CH2Cl2), getting a white solid (6.3 g, yield 93%), MS (ESI): mass calculated for C16H23NO4, 293,16; found m/z 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), of 1.17 (t, J=7,2, 3H).

CenturyEthyl ester of 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

CH3CN (34 ml) add CS2CO3(5 g, and 14.3 mmol) and 2-chlorobenzothiazole (1,26 ml, 10.2 mmol). The reaction mixture is heated to 75ºC for 3 h, then cooled to room temperature and filtered. The filtrate is concentrated under reduced pressure. The residue is dissolved in CH2Cl2and purified on SiO2(40 g; 0-25% acetone/CH2Cl2)to give white solid (2,94 g, yield 100%). MS (ESI): mass calculated for C23H26N2O4S, 426,16; found m/z 427,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, J=8,0, 1H), to 7.64 (t, J=8,1, 1H), 7,41 (t, J=8,4, 1H), 7,30 (d, J=9,0, 3H), 7,05 (d, 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), 2,37 (m, 1H, in), 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 m is) add trimethylsilanol potassium (282 mg, 2.2 mmol). The reaction mixture was stirred at room temperature for 2 h, then concentrated under reduced pressure. The oil obtained is dissolved in H2Oh and the solution is treated with 1M HCl to pH 9. The resulting solution was extracted with a mixture of 1:3 isopropyl alcohol/chloroform (3×25 ml). The combined extracts are concentrated under reduced pressure, obtaining a yellowish-brown solid, which was triturated in diethyl ether. Filtering the suspension gives a yellowish-brown solid (140 mg, yield 64%). MS (ESI): mass calculated for C21H22N2O4S (free acid), 398,13; found m/z 399,1 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,01 (d, J=7,3, 1H), 7,76 (d, J=7,5, 1H), 7,51 (t, J=8,4, 1H), 7,45 (d, J=9,0, 2H), 7,40 (t, J=7,2, 1H), 7,14 (d, 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 CHCl3(2 ml) add oxalicacid (132 μl, 1.5 mmol). The reaction mixture was stirred at room temperature for 2 hours and then concentrated under reduced pressure. The obtained solid substance resuspending in CHCl3(2 ml) and add pyrrolidine (100 m is l, 1.2 mmol). The resulting solution is stirred for 1 h, then diluted with CH2Cl2(10 ml) and washed with saturated aqueous NaHCO3(10 ml). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure to a yellow oil. The crude oil is purified on SiO2(10 g; 0-100% acetone/CH2Cl2)to give the desired product as a colourless oil (71 mg, yield 63%). MS (ESI): mass calculated for C25H29N3O3S, 451,19; found m/z 452,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=7,6, 1H), 7,66 (DD, J=8.0 a, 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, 2H), and 2.83 (t, J=6,0, 2H), 2,38-2,31 (m, 1H), 2,21 with 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

Hydrate 1-hydroxybenzotriazole (HOBT; 1.0 ml, 0,5M 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 (EDCl; 150 mg, 0,785 mmol) are successively added at intervals of 5 min 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 is stirred over night at room temperature. Reactio the ing the mixture was diluted with CH 2Cl2(10 ml) and washed with saturated aqueous NaHCO3(10 ml), then H2About (10 ml). The organic layer is dried (Na2SO4), filtered and concentrated under reduced pressure, receiving no white semi-solid substance. The crude residue purified on SiO2(35 g; 0-5% 2M NH3in a mixture of CH3OH/CH2Cl2)to give the desired product as a white solid (186 mg, yield 48%). MS (ESI): mass calculated for C26H31N3O5S, 497,20; found m/z 498,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (DD, J=8,1, 0,6, 1H), 7,66 (DD, 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), of 1.28 (t, J=7,2, 3H).

EXAMPLE 21

(1-{2-[4-(Benzoxazol-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) add K2CO3(7,1 g, 51,4 mmol). The mixture is heated at boiling under reflux for 20 h and then filtered. The filtrate is concentrated under reduced pressure to a clear Golden oil, which was purified on SiO2(120 g; 0-100% acetone/CH2Cl2)to give 60 g (yield 77%) of white solids. TLC (SiO2, acetone): Rf=0,15. MS (ESI): mass calculated for C21H27NO3, 341,20; found m/z 342,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): of 7.48-7,25 (m, 5H), 6,92 (d, J=9,1, 2H), 6,85 (d, J=9,1, 2H), 5,02 (c, 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 (d, J=9,4, 2H), 1,52-of 1.44 (m, 1H), 1,44 to 1.31 (m, 1H), 1,30-1,17 (m, 2H).

B.4-[2-(2-Hydroxyethylpiperazine-1-yl)ethoxy]phenol

To a solution of {1-[2-(4-benzyloxyphenyl)ethyl]piperidine-2-yl}methanol (6.0 g, 17.6 mmol) in a mixture of 1:1 ethanol/ethyl acetate (75 ml) is added Pd on carbon (10 wt.%, 614 mg). The mixture is placed in hydrogenator Parra at a pressure of H240 lb/in2and hydronaut for 20 hours, the Reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, receiving 4.5 g (yield 100%) of the desired product as a clear colorless oil. TLC (SiO2, acetone): Rf=0,29. MS (ESI): mass calculated for C14H21NO3, 251,15; found m/z 252,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 6,77 (d, J=6,6, 2H), of 6.68 (d, 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}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 ,15 mmol) in acetone (10 ml) was stirred at room temperature for 20 hours The resulting mixture was filtered through a layer of diatomaceous earth. Layer washed with acetone and the combined filtrates concentrated under reduced pressure, getting a Golden oil. The oil is purified on SiO2(10 g; 0-100% acetone/CH2Cl2)to give the desired product as a clear colorless oil (202 mg, 70%). TLC (SiO2, acetone): Rf=0,17. MS (ESI): mass calculated for C21H24N2O3S, 384,15; found m/z 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 (d, J=9,1, 4H), 7,35-7,30 (m, 4H), 7,03 (d, 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), of 1.62 (d, 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 heated to 70ºC for 18 hours, the Reaction mixture was filtered and the collected resin was washed with CH3CN. The combined filtrates are concentrated under reduced pressure to a crude solid, which was purified on SiO2(10 g; 0-100% 10% [2M NH3in CH3OH] CH2Cl2)to give 142 mg (yield 63%) of white solids. MS (ESI): mass, calc is slena for C 21H23N3O3S, 397,15; found m/z 398,4 [M+H]+.

1H NMR (400 MHz, CDCl3): a 7.85 (DD, J=8.0 a, 0,3, 1H), of 7.75 (DD, J=8.0 a, 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 (userd, J=47, 2H), 4,15 (t, J=5,8, 2H), 3,09 (userd, J=8,8, 2H), 2,85 (t, J=5,7, 2H), 2,28-2,12 (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 heated to 70ºC for 18 hours, the Reaction mixture was filtered and the collected resin was washed with CH3CN. The combined filtrates are concentrated under reduced pressure to a crude solid, which was purified on SiO2(10 g; 0-100% 10% [2M NH3in CH3OH] CH2Cl2getting not quite sticky white solid (142 mg, yield 63%). MS (ESI): mass calculated for C24H27N3O3S, 337,18; found m/z 348,5 [M+H]+.

1H NMR (400 MHz, CDCl3): a 7.85 (DD, J=8.0 a, 0,5, 1H), of 7.75 (DD, J=8.0 a, 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 (userd, J=48,8, 2H), 3,80-the 3.65 (m, 1H), 3,40 (t, J=7,0, 1H), 3,30-3,10 (users, 1H), 3.15 and, (kV, J=7,2, 1H), 2,96 (users, 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 (d, 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]benzothiazole (example 9; 542 mg, 1.55 mmol) and hydrochloride [1,4']bipyridinyl-2-it (371 mg, was 1.69 mmol) in CH3CN (20 ml) add K2CO3(517 mg, 3,74 mmol). The mixture is heated at the boiling point under reflux for 20 h and then filtered. The filtrate is concentrated under reduced pressure to a clear Golden oil, which was purified on SiO2(10 g; 0-100% acetone/CH2Cl2)to give 294 mg (yield 42%) of white solids. TLC (SiO2, acetone): Rf=0,15. MS (ESI): mass calculated for C25H29N3O3S, 451,19; found m/z 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 (d, J=9,0, 2H), 7,31 (t, J=7,3 2H), 7,06 (d, 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 for (d, J=11,5, 2H), 2,71 (t, J=5,7, 2H), of 2.21 (t, J=6,5, 2H), 2,10 (t, J=11,4, 2H), 1,75 is 1.58 (m, 6H), USD 1.43 (d, J=10,0, 2H).

EXAMPLE 25

8-{2-[4-(Benzothiazol-2-yloxy)phenoxy]ethyl}-2,8-diazaspiro[4.5]Decan-1-he

A solution of 2-[4-(2-bromoethoxy)phenoxy]benzothiazole (example 9; 257 mg, 0.73 mmol), hydrochloride of 2.8-diazaspiro[4.5]Decan-1-she (153 mg, 0.80 mmol) and dimethylamino resin Silicycle® (1.7 g, 2.4 mmol) in CH3CN heated to 80ºC for 18 hours, the Reaction mixture was filtered and the collected resin was washed with CH3CN. The combined filtrates are concentrated under reduced allowing the attachment to untreated solids, which cleanse SiO2(10 g; 0-100% 10% [2M NH3in CH3OH] CH2Cl2), receiving not quite white solid (152 mg, yield 49%). MS (ESI): mass calculated for C23H25N3O3S, 423,16; found m/z 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 a, 0,8, 1H), 7,41 (dt, J=7,5, 1,3, 1H), 7,32-7,27 (m, 3H), 7,00 (m, 2H), 6,36 (users, 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 (userd, J=13.3-inch, 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) added pyrrolidine (2.0 ml, 24,0 mmol) in CH3CN. The mixture is stirred for 20 h, then concentrated under reduced pressure to a yellow oil, which was purified on SiO2(35 g; acetone)to give 1.2 g (yield 80%) of the desired product as a white solid. TLC (SiO2, acetone): Rf=0,05. MS (ESI): mass calculated for C20H25NO2, 311,19; found m/z 312,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50-7,30 (m, 5H), of 6.90 (d, J=9,1, 2H), PC 6.82 (d, J=9,1, 2H), 5,02 (c, 2H), 4.00 points (t, J=6,1, 2H), from 3.0 to 2.75 (m, 6H), of 2.15 (d, J=6,2, 2H), 1,94 (users, 4H).

B.4-(3-Pyrrolidin-1 ipropose)phenol

To a solution of 1-[3-(4-benzyloxyphenyl)propyl]pyrrolidine (1.2 g, 3.9 mmol) in with the art 1:1 ethanol/ethyl acetate (65 ml) is added Pd on carbon (10 wt.%, 206 mg). The mixture is placed in hydrogenator Parra at a pressure of H240 lb/in2and hydronaut for 20 hours the mixture is filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, getting 875 mg (yield 100%) of the desired product as a brown solid. MS (ESI): mass calculated for C13H19NO2, 221,14; found m/z to 222.2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,90 (c, 1H), 6,74 (d, J=9,0, 2H), 6,65 (d, J=9,0, 2H), 3,90 (t, J=6,3, 2H), 2,72 (users, 6H), 1,90 (quintet, J=7,4, 2H), 1,76 (c, 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 (5 ml)containing Cs2CO3(213 mg, of 0.65 mmol), is added 2-chlorobenzothiazole (65 μl, 0.50 mmol). The mixture is heated at the boiling point under reflux for 24 h and then filtered. The filtrate is concentrated under reduced pressure to a clear Golden oil, which was purified on SiO2(10 g; acetone)to give 97 mg (yield 61%) of the desired product. TLC (SiO2, acetone): Rf=0,02. MS (ESI): mass calculated for C20H22N2O2S, 354,14; found m/z 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 (users, 4H), 2,04 (quintet, J=6,5, 2H), 1,82 (users, 4H).

EXAMPLE 27

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

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

4-(3-Bromopropane)phenol (example 4; 3 g, 13 mmol) dissolved in CH3CN (65 ml). To the resulting solution was added 4-hydroxy-4-phenylpiperidine (6.8 g, 39 mmol) and the mixture is stirred at room temperature overnight, obtaining a white precipitate. The suspension is filtered, getting mentioned in the title compound as a white solid (5 g, to 11.9 mmol, yield 91%). MS (ESI): mass calculated for C20H25NO3(free base), 327,18; found m/z 328,2 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,49 (d, J=7,5, 2H), 7,32 (t, J=7,5, 2H), 7,21 (t, J=7,2, 1H), 6.73 x (kV, J=12,3, 4H), of 3.96 (t, J=6,1, 2H), 2,85 (d, J=11,3, 2H), 2,64-of 2.54 (m, 4H), to 2.13 (dt, J=9,0, 3,9, 2H), 2,00 (m, 2H), 1,75 (d, J=12,2, 2H).

B.1-{3-[4-(Benzoxazol-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) add Cs2CO3(1,03 g and 3.15 mmol). The resulting suspension is cooled to 0ºC and added dropwise 2-chlorobenzoxazole (276 mg, 1.8 mmol, 0.2 ml). The reaction mixture allow to warm to room temperature overnight, then filtered and concentrated under reduced pressure. The oil obtained is dissolved in CHsub> 2Cl2and purified on SiO2(40 g; 0-100%

acetone/CH2Cl2)to give 450 mg (1.05 mmol, yield 70%) of white solids. MS (ESI): mass calculated for C26H26N2O4, 444,20; found m/z 445,20 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,47-the 7.43 (m, 3H), of 7.36-7,11 (m, 8H), of 6.90 (d, J=9,1, 2H), 3,99 (t, J=5,8, 2H), 2,80 (d, J=9,5, 2H), has 2.56 (t, J=6,8 Hz, 2H), 2,44 (t, J=10,9, 2H), 2,13 (t, J=11,0, 2H), up to 1.98 (m, J=6,8, 2H), 1,71 (d, J=6,9, 2H).

EXAMPLE 28

1-{3-[4-(Benzoxazol-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) are 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 overnight, obtaining a white precipitate. The suspension is filtered and the filtrate concentrated under reduced pressure. The resulting oil purified on SiO2(10 g; 0-100%

acetone/CH2Cl2)to give 110 mg (0.32 mmol, yield 25%) of a white solid. MS (ESI): mass calculated for C21H22NO3, 341,20; found m/z 342,2 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.36-7,24 (m, 3H), 7,22 (d, J=6,9, 2H), 6,7 (m, 4H), 4,07 (t, J=6,5, 2H), 3,41 (d, J=11,7, 2H), 3,19 (t, J=7,8, 2H), 3,11 (t, J=11.8 in, 4H), 2,84 (users, 2H), 2,34 (users, 4H), 2,18 (users, 1H), 1,72 (d, 14,5, 2H).

B.1-{3-[4-(Benzoxazol-2-yloxy)phenoxy]propyl}-4-bentilee the one-4-ol

To a stirred solution of 4-benzyl-1-[3-(4-hydroxyphenoxy)propyl]piperidine-4-ol (2.5 g, 7,3 mmol) in acetone (37 ml) add Cs2CO3(4,99 g of 15.3 mmol). The resulting suspension is cooled to 0ºC and added dropwise 2-chlorobenzoxazole (1.1 ml, 9.5 mmol). The reaction mixture allow to warm to room temperature over night, filtered and then concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and purified on SiO2(110 g; 0-100% acetone/CH2Cl2)to give 310 mg (0.67 mmol, yield 9%) of white solids. MS (ESI): mass calculated for C28H30N2O4, 458,2; found m/z 459,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,49 (d, J=7,2, 1H), 7,41 (d, J=7,2, 1H), 7,35-to 7.18 (m, 9H), 6,94 (d, J=9,1, 2H), Android 4.04 (t, J=6,5, 2H), 2.93 which is 2.45 (m, 7H), 2,16 (c, 4H), 1,60 (d, J=13,0, 2H), 1,29 (users, 1H).

EXAMPLE 29

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

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

A solution of 4-(2-bromacil)phenol (example 5; 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 CH3CN (100 ml) was stirred at 60ºC for 18 h the resulting solution was cooled to room temperature and concentrated under reduced pressure, obtaining a pale orange solid. Add diethyl ether (100 ml) and specified in the header soedineniya by filtration in the form of not-quite-white solid (4.6 g, crude yield 100%). TLC (SiO2with 5% 2M NH3in a mixture of CH3OH/CH2Cl2): Rf=0,19. MS (ESI): mass calculated for C13H19NO2, 205,15; found m/z 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).

Century2-[4-(2-piperidine-1-retil)phenoxy]benzoxazol

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 a layer of diatomaceous earth, washed with CH2Cl2. The combined filtrates are concentrated under reduced pressure to an orange oil, which was purified on SiO2(40 g; 0-100% acetone/CH2Cl2)to give the desired product as a white solid (325 mg, yield 42%). TLC (SiO2with 5% 2M NH3in a mixture of CH3OH/CH2Cl2: Rf=0,36. MS (ESI): mass calculated for C20H22N2O2, 322,17; found m/z 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 (users, 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-(Cyclohexylethylamine)this is]phenol

To a stirred solution of 4-(2-bromacil)phenol (example 5; 4,48 g of 22.3 mmol) in CH3CN (100 ml) add cyclohexylethylamine (5.0 ml, 33.4 mmol) followed by addition of N,N-diisopropylethylamine (7,76 ml and 44.6 mmol). The resulting solution was stirred at 60ºC for 16 h, obtaining a suspension. Suspension allow to cool to room temperature and filtered. The filtered solid is washed with ethyl acetate (2×20 ml) and dried, obtaining white solid (4.8 g, yield 87%). MS (ESI): mass calculated for C16H25NO, 247,19; found m/z 248,2 [M+H]+.

1H NMR: (400 MHz, CDCl3): 7,01 (d, J=8,6, 2H), 6.87 in (d, 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).

B.{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}cyclohexylethylamine

To a stirred solution of 1-[2-(4-hydroxyphenoxy)ethyl]piperidine-4-ol (495 mg, 2.0 mmol) in DMF (10 ml) add Cs2CO3(1.3 g, 4.0 mmol) and 2-chlorobenzothiazole (0.33 ml, 2.5 mmol). The suspension is stirred at 80ºC overnight. The reaction mixture allow to cool to room temperature and then filtered through a layer of diatomaceous earth. The filtrate is concentrated under reduced pressure and the residue purified on SiO2(40 g; 0-100% acetone/CH2Cl2), getting 548 mg (yield 72%) of a yellowish brown solid. MS (ESI): mass calculated for C23H28 N2OS, 380,19; found m/z 381,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,0, 1H), 7,63 (d, J=8,0, 1H), 7,30 (t, 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 heated to 70ºC for 18 hours, the Reaction mixture was filtered and the collected resin was washed with CH3CN. The combined filtrates are concentrated under reduced pressure to a crude solid, which was purified on SiO2(10 g; 0-100% 10% [2M NH3in CH3OH] CH2Cl2)to give 135 mg (yield 47%) of white solids. MS (ESI): mass calculated for C21H23N3O2S, 381,15; found m/z 382,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 8,10 (d, J=8,1, 1H), of 7.75 (DD, J=8.0 a, 0,8, 1H), 7,42 (dt, J=7,4, 1,3, 1H), 7,21 (users, 1H) 6.42 per (users, 1H), 3,05 (userd, 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 (d, J=11,5, 1H), 2,08 (t, J=10,5, 1H), 1,98 (d, 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 the-2-yloxy)phenyl]ethyl ester toluene-4-sulfonic acid

To a stirred solution of 2-[4-(benzothiazol-2-yloxy)phenyl]ethanol (example 10; 12,25 g of 45.2 mmol) in CH2Cl2(225 ml) is added p-toluensulfonate (17,23 g, 90 mmol) and TEA (31 ml, 225 mmol). The mixture is stirred at room temperature for 72 h, the Reaction mixture was concentrated under reduced pressure and the residue is dissolved in ethyl acetate (400 ml). The solution was washed with saturated aqueous NaHCO3(3×200 ml), dried (Na2SO4) and concentrate under reduced pressure. The resulting oil was dissolved in CH2Cl2and clean SiO2(300 g; CH2Cl2), receiving a yellowish-brown solid (8.8 g, yield 45%). MS (ESI): mass calculated for C22H19N2O4S2, 425,08; found m/z 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), to 4.23 (t, J=6,9, 2H), 2,99 (d, J=6,9, 2H), 2,43 (c, 3H).

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

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 purified on SiO2(12 g; 50% acetone/CH2Cl 2), getting a clear oil (16 mg, yield of 3.3%). MS (ESI): mass calculated for C28H28N4O2S, 484,19; found m/z 485,5 [M+H]+.

1H NMR (400 MHz, CD3OD): of 7.75 (d, J=7,9, 1H), 7,65 (d, J=8,1, 1H), 7,41-7,29 (m, 7H), 7,13 (m, 3H), 4,37 (m, 1H), 3,40 (c, 3H), of 3.25 (d, J=11.8 in, 2H), equal to 2.94 (m, 2H), 2,75 (m, 2H), 2.57 m (kV, d, J=12,6, 3,7, 2H), 2,33 (t, J=11,3, 2H), 1,81 (d, J=12,2, 2H).

EXAMPLE 33

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

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

To a stirred solution of 4-(2-bromacil)phenol (example 5; of 5.05 g, 25 mmol) in CH3CN (100 ml) is added methyl ether piperidine-4-carboxylic acid (5,07 ml, 37.5 mmol) followed by addition of N,N-diisopropylethylamine (8.7 ml, 50 mmol). The reaction mixture was stirred at 60ºC for 16 h and then the mixture allow to cool to room temperature. Add CH2Cl2(250 ml) and the resulting solution was washed with H2About (2×30 ml), dried, filtered and then concentrated under reduced pressure, obtaining of 5.2 g (79%) of a yellowish brown solid. MS (ESI): mass calculated for C15H21NO3, 263,15; found m/z 264,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 6,97 (d, J=8,2, 2H), 6,70 (d, J=8,6, 2H), 3,67 ,(c, 3H), 2,99 (d, 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).

B.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) add Cs2CO3(of 1.95 g, 6.0 mmol) and 2-chlorobenzothiazole (of 0.47 ml, 3.9 mmol). The suspension is heated to 100ºC and stirred over night. The reaction mixture allow to cool to room temperature and then filtered through a layer of diatomaceous earth. The filtrate is concentrated under reduced pressure and the residue purified on SiO2(40 g; 0-100% acetone/CH2Cl2)to give 1.04 g (yield 87%) of a yellowish brown solid. MS (ESI): mass calculated for C22H24N2O3S, 396,15; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=7,8, 1H), 7,65 (d, J=7,8, 1H), 7,38 (t, J=7,6, 1H), 7,28-7,25 (m, 5H), 3,69 (c, 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.Salt triperoxonane acid 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 3:1 THF/CHsub> 3OH (100 ml) is added lithium hydroxide (1.1 g, with 46.6 mmol) in H2O (25 ml). The obtained dark-yellow solution was stirred at room temperature for 16 h and then concentrated under reduced pressure. The residue is dissolved in CH3OH and purified HPLC with reversed phase, getting mentioned in the title compound as a pale yellow solid (3.9 g, yield 68%). MS (ESI): mass calculated for C21H22N2O3S, 382,14; found m/z 383,4 [M+H]+.

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

To a mixture of TFA salt of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid (300 mg, 0.6 mmol) in CH2Cl2(15 ml) and a drop of DMF add oxalicacid (of 0.11 ml, 1.2 mmol). The mixture is stirred at room temperature for 1 h the resulting mixture was concentrated under reduced pressure. The residue is dissolved in CH2Cl2(15 ml) and add N-methylpiperazine (0.2 ml, 1.8 mmol). The reaction mixture was stirred at room temperature for 1 h, diluted with CH2Cl2(100 ml), washed with H2Oh, saturated aqueous NaHCO3then a saturated solution of salt, dried (Na2SO4) and filtered. The filtrate is concentrated under reduced pressure and the residue purified on SiO2(40 g; 0-10% 2M NH3in a mixture of CH3OH/CH2Cl2), receiving is shown in the title compound (240 mg, 86%). MS (ESI): mass calculated for C26H32N2O3S, 464,22; found m/z 465,5 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,72 (d, J=7,6, 1H), 7,65 (d, J=7,6, 1H), 7,37 (t, J=7,6, 1H), 7,29-7,22 (m, 5H), 3,64 (users, 2H), 3,51 (users, 2H), 3,06 (d, 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), 2,30 (c, 3H), of 2.06 (t, J=12,1, 2H), 1,99-of 1.84 (m, 2H), 1,72 (d, J=13,1, 2H).

EXAMPLE 35

{3-[4-(Benzoxazol-2-yloxy)phenyl]propyl}cyclohexylethylamine

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) add K2CO3(510 mg, of 3.69 mmol). The reaction mixture is heated at the boiling point under reflux for 20 hours the Mixture is filtered and then concentrated under reduced pressure to a Golden oil, which was purified on SiO2(10 g; 50% acetone/CH2Cl2), getting 484 mg (yield 83%) of the desired product as a clear colorless oil. TLC (SiO2, acetone): Rf=0,13. MS (ESI): mass calculated for C24H33NO, 351,26; found m/z 352,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50-7,28 (m, 5H), 7,12 (d, J=8,6, 2H), make 6.90 (d, J=8,6, 2H), 5,06 (c, 2H), 2,60 at 2.45 (m, 7H), 1,78 (users, 6H), 1,20 (users, 4H), of 1.05 (t, J=7,1, 4H).

B.4-[3-(Cyclohexylamino)propyl]phenol

To a solution of [3-(4-benzyloxyphenyl)propyl]cycle is hexadecylamine (420 mg, 1,19 mmol) in a mixture of 1:1 ethanol/ethyl acetate (16 ml) is added Pd on carbon (10 wt.%, 46 mg). The mixture is placed in hydrogenator Parra at a pressure of H240 lb/in2and hydronaut for 20 hours the mixture is filtered through a layer of diatomaceous earth and concentrated under reduced pressure, getting 308 mg (yield 99%) of the desired product as a Golden oil. TLC (SiO2, acetone): Rf=0,18. MS (ESI): mass calculated for C17H27NO, 261,21; found m/z 262,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,00 (d, J=8,5, 2H), 6.75 in (d, J=8,5, 2H), 2,65 (users, 5H), of 2.54 (t, J=7,6, 2H), 1,82 (users, 6H), 1.30 and of 1.05 (m, 8H).

C.{3-[4-(Benzoxazol-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 5ºC add 2-chlorobenzoxazole (155 μl, of 1.36 mmol). The reaction mixture allow to warm to room temperature overnight, then filtered. The filtrate is concentrated under reduced pressure to a Golden oil, which was purified on SiO2(10 g; acetone)to give 333 mg (yield 81%) of the desired product as a Golden oil. TLC (SiO2, acetone): Rf=0,12. MS (ESI): mass calculated for C24H30N2O2, 378,23; found m/z 379,3 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.61 (d, J=7,3, 1H), 7,49 (d, J=7,8, 1H), 7,39 (d, J=8,6, 2H), 7,38-7,25 (m, 4H), 2,62 (t, J7,5, 2H), 2,65 to 2.35 (m, 8H), 1,67 (users, 5H), 1,19-1,10 (m, 4H), of 0.95 (t, J=7,1, 3H).

EXAMPLE 36

1-{3-[4-(Benzoxazol-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 mg, 6.6 mmol) and N,N-diisopropylethylamine (2.2 ml, 12.3 mmol) in CH3CN (20 ml) was stirred at 60ºC for 18 hours, the Reaction mixture was cooled to room temperature and the solvent is removed under reduced pressure, getting not quite white solid. The resulting material was dissolved in CH2Cl2(200 ml) and the solution washed with N2About (2×50 ml), dried (Na2SO4), filtered and concentrated under reduced pressure, obtaining a white solid. Add diethyl ether and indicated in the title compound collected by filtration (1.4 g, yield 90%). TLC (SiO2with 5% 2M NH3in a mixture of CH3OH/CH2Cl2: Rf=0,05. MS (ESI): mass calculated for C14H21NO2, 235,16; found m/z 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).

B.1-{3-[4-(Benzoxazol-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) is Cs 2CO3(1.45 g, of 4.45 mmol) in acetone (8.0 ml) was stirred at room temperature for 48 hours the mixture is filtered through a layer of diatomaceous earth, which is then washed with CH2Cl2. The combined filtrates are concentrated under reduced pressure, obtaining a yellow oil. The oil is purified on SiO2(40 g; 0-100% acetone/CH2Cl2)to give white solid, which was dissolved in CH2Cl2. The solution was washed with 1M NaOH (3×5 ml), then H2O (5 ml), dried (Na2SO4), filtered and concentrated under reduced pressure, obtaining mentioned in the title compound as a white solid (98 mg, yield of 16.4%). TLC (SiO2with 5% 2M NH3in a mixture of CH3OH/CH2Cl2: Rf=0,14. MS (ESI): mass calculated for C21H24N2O3, 352,18; found m/z 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), of 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-Benzimidazole-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 CH3CN (150 ml) is added DIEA (7.0 ml, with 40.2 mmol). The mixture is stirred tip is of 20 h at room temperature and for an additional 4 h at 65ºC, then concentrate under reduced pressure, obtaining a brown solid. The solid is dissolved in ethyl acetate (250 ml), the solution washed with H2O (250 ml, 100 ml), dried (MgSO4) and concentrated under reduced pressure, obtaining a brown solid. The solid is purified on SiO2(120 g; 0-100% acetone/CH2Cl2), receiving of 8.9 g (yield 77%) of the desired product as a yellowish brown solid. TLC (SiO2, acetone): Rf=0,42. MS (ESI): mass calculated for C19H23NO3, 313,17; found m/z 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 (c, 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 (d, J=11.8 in, 2H).

B.4-Phenyl-1-(2-{4-[1-(2-trimethylsilylethynyl)-1H-benzimidazole-2-idoxifene}ethyl)piperidine-4-ol

To a mixture of 2-chloro-1-(2-trimethylsilylethynyl)-1H-7-benzimidazole (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) add Cs2CO3(1.5 g, 4.6 mmol). The reaction mixture was stirred at 100ºC for 18 h and then distribute the mixture in 1:1 ethyl acetate/N2About (50 ml). The organic layer collected, dried (MgSO4) and concentrate under reduced pressure to a clear brown oil, which was purified on SiO2(35 g; acetone), getting 867 mg (yield 70%) is Elenovo product in the form of a clear Golden oil. TLC (SiO2, acetone): Rf=0,38. MS (ESI): mass calculated for C32H41N3O4Si, 559,29; found m/z 560,3 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.55 (m, 3H), 7,38 (m, 3H), 7,30-7,20 (m, 5H), of 6.99 (d, J=9,0, 2H), 5,55 (c, 2H), 4,17 (t, J=5,9, 2H), 6,37 (m, 2H), 2,92 (m, 5H), to 2.65 (t, J=12,4, 2H), of 2.21 (t, J=15,9, 2H), 1,81 (d, J=12,1, 2H), of 0.96 (t, J=8,1, 2H).

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

To a solution of 4-phenyl-1-(2-{4-[1-(2-trimethylsilylethynyl)-1H-benzimidazole-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), add a 1M solution of tetrabutylammonium fluoride in THF (TBAF, 15 ml, 15 mmol). The mixture was stirred at 55ºC for 5 h, then concentrated under reduced pressure. The oil obtained is dissolved in diethyl ether (100 ml) and the solution washed with N2About (3×75 ml), dried (MgSO4), filtered and concentrated under reduced pressure, obtaining a white solid. Add diethyl ether and filtration gives the desired product as a white solid (155 mg, yield 25%). TLC (SiO2, acetone): Rf=0,16. MS (ESI): mass calculated for C26H27N3O3, 429,21; found m/z 430,2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,23 (users, 1H), of 7.48 (d, J=7,3, 2H), 7,35-7,25 (m, 6H), 7,20 (t, J=7,4, 1H), 7,10? 7.04 baby mortality (m, 2H), 7,00 (d, J=9,0, 2H), 4,80 (c, 1H), 4,13 (t, J=5,8, 2H), was 2.76 (t, J=5,8, 2H), 2,58-2,48 (m, 2H), 1,94 (dt, =12,7, 4,0, 2H), 1,58 (d, J=12,1, 2H).

EXAMPLE 38

{2-[4-(1H-Benzimidazole-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 CH3CN (100 ml) add cyclopropanemethylamine (5,4 ml, 37.5 mmol) followed by addition of N,N-diisopropylethylamine (to 8.70 ml, 50.0 mmol). The resulting solution was stirred at 60ºC for 16 h, obtaining a suspension which is cooled to room temperature and filtered. The filtered solid is washed with ethyl acetate (2×20 ml) and dried, obtaining white solid (5.7 g, yield 98%). MS (ESI): mass calculated for C15H23NO, 233,18; found m/z 234,1 [M+H].

1H NMR (400 MHz, DMSO-d6): 7,01 (d, J=8,6, 2H), 6.87 in (d, 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).

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

A mixture of 2-chloro-1-(2-trimethylsilylethynyl)-1H-benzimidazole (example 7; 707 mg, 2.5 mmol), 4-[2-(cyclopropylamino)ethyl]phenol (467 mg, 2.0 mmol) and Cs2CO3(1.3 g, 4.0 mmol) in DMF (10 ml) was stirred at 100ºC for 18 hours, the Reaction mixture was cooled to room temperature and then distribute the mixture in 1:1 ethyl acetate/H2O (200 ml). The organic layer is collected, the tub (MgSO 4) and concentrate under reduced pressure to a clear brown oil, which was purified on SiO2(40 g; 0-100% acetone/CH2Cl2getting 729 mg (yield 76%) as a clear Golden oil. MS (ESI): mass calculated for C28H41N3O2Si, 479,30; found m/z 480,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,63-7,58 (m, 1H), 7,49-7,39 (m, 1H), 7,31 (c, 4H), 7,26-7,22 (m, 2H), 5,58 (c, 2H), 3,69 (t, J=8,2, 2H), 2,89-and 2.79 (m, 4H), 2,63-of 2.58 (m, 2H), 2,48 (d, 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 (c, 9H).

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

To a solution of cyclopropylmethanol(2-{4-[1-(2-trimethylsilylethynyl)-1H-benzimidazole-2-yloxy]phenyl}ethyl)amine (411 mg, 0.87 mmol) in THF (5 ml) is added via syringe TBAF (1M in THF, to 2.57 ml, 2.57 mmol) and the mixture is stirred at the boil under reflux for 16 hours, the Reaction mixture was cooled to room temperature and concentrate under reduced pressure. The resulting oil purified on SiO2(40 g; 0-20% CH3OH/CH2Cl2getting 284 mg (yield 95%) of a clear oil. MS (ESI): mass calculated for C22H27N3O, 349,22; found m/z 350,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,34 (users, 2H), 7.18 in-7,05 (m, 6H), 2,82-2,70 (m, 4H), 2,69-2,62 (m, 2H), 2,52 (d, 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

Qi is logicality{2-[4-(1-methyl-1H-benzimidazole-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 100ºC for 16 hours, the Reaction mixture was cooled and filtered through a layer of diatomaceous earth, which is then washed with ethyl acetate (30 ml). The combined filtrates washed with N2About (3×10 ml), then saturated salt solution (10 ml), dried (Na2SO4), filtered and concentrated under reduced pressure. The crude substance is purified on SiO2(10 g; 0-100% 10% [2M NH3in CH3OH] CH2Cl2)to give 105 mg (yield 28%) of brown oil. MS (ESI): mass calculated for C24H31N3O, 377,53; found m/z 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 (c, 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 (d, J=12,3, 1H), 1,35-of 1.18 (m, 4H), 1,15-1,05 (m, 1H), 1,12 (t, J=7,1, 3H).

EXAMPLE 40

1-{3-[4-(Benzoxazol-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) add Cs2CO3(51,2 g, 157 mmol). The mixture is heated at 75ºC for 3 days. The reaction mixture is cooled to room temperature and then distribute in a mixture of 1:1 etelaat the/H 2O (600 ml). The organic layer is collected, washed with N2About (3×250 ml), dried (MgSO4), filtered and concentrated under reduced pressure, receiving 38 g transparent dark brown liquid. The liquid is purified on SiO2(300 g; 50-100% CH2Cl2/hexane)to give the desired product as a white solid (13 g, yield 68%). TLC (SiO2CH2Cl2): Rf=0,64.

1H NMR (400 MHz, CDCl3): 7,55-7,28 (m, 5H), 6,91 (d, J=9,3, 2H), 6,86 (d, J=9,3, 2H), 5,03 (c, 2H), 4,17 (DD, J=11,0, 3,2, 1H), 3.95 to 3,88 (m, 1H), 3,36-to 3.33 (m, 1H), only 2.91 (t, J=4,8, 1H), 2,75 (DD, J=4,9, 2,6, 1H).

B.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 CH3CN (50 ml) add K2CO3(1.0 g, of 7.23 mmol). The mixture is heated at the boiling point under reflux for 20 hours, the Reaction mixture was filtered and the filtrate concentrated under reduced pressure to a white solid, which was purified on SiO2(40 g; acetone)to give 1.4 g (yield 56%) of the desired product as a white solid. TLC (SiO2, acetone): Rf=0,36. MS (ESI): mass calculated for C27H31NO4, 433,23; found m/z 434,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,56-of 7.23 (m, 10H), 6,93 (d, J=9,2, 2H), to 6.88 (d, J=9,2, 2H), 5,03 (c, 2H), 4,77 (c, 2H), 3,93 (userd, J=10,8, 2H), 3,81 (t, J=7,2, 1H), 2,80-2,60 (who, 2H), 2,50 to 2.35 (m, 4H), 1,97-1,90 (m, 2H), 1.60-to 1,50 (d, 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 1:1 ethanol/ethyl acetate (50 ml) is added Pd on carbon (10 wt.%, 165 mg). The mixture is placed in hydrogenator Parra at a pressure of H240 lb/in2and hydronaut for 20 hours, the Reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, obtaining 1.0 g (yield 100%) of the desired product as a white solid. TLC (SiO2, acetone): Rf=0,27. MS (ESI): mass calculated for C20H25NO4, 343,18; found m/z 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 (t, J=7,3, 1H), make 6.90 (d, J=9,0, 2H), for 6.81 (d, J=9,0, 2H), 4,25 (users, 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)that is 1.81 (d, J=11.8 in, 2H).

D.1-{3-[4-(Benzoxazol-2-yloxy)phenoxy]-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 5ºC add 2-chlorobenzoxazole (108 μl, 0.95 mmol). The reaction mixture was left on ice, warmed to room temperature overnight and then filtered. The filtrate is concentrated under reduced pressure until Golden oil that PTS who participate on SiO 2(10 g; acetone)to give 127 mg (yield 38%) of the desired product as a white solid. TLC (SiO2, acetone): Rf=0,27. MS (ESI): mass calculated for C27H28N2O5, 460,20; found m/z 461,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,60 (d, J=6,6, 1H), 7,55-to 7.35 (m, 5H), 7,32-7,25 (m, 4H), 7,20 (t, J=7,3, 1H), 7,06 (d, J=9,1, 2H), 4,78 (c, 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 (d, J=13,2, 2H).

EXAMPLE 41

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

A.4-Benzoxazol-2-ylmethylene

A mixture of 4-hydroxyphenylarsonic acid (35 g, 230 mmol) and 2-aminophenol (43 g, 400 mmol) is heated at 180ºC for 3 h and then cooled to room temperature. The obtained solid is pulverized, dissolved in THF (200 ml) and add carbonyldiimidazole (27 g, 170 mmol). The solution was stirred at 60ºC overnight. The reaction mixture was concentrated under reduced pressure and distributed between ethyl acetate (400 ml) and N2O (300 ml). The organic layer is concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and purified on SiO2(200 g; 0-50% acetone/CH2Cl2)to give a brown solid (31 g, yield 40%). MS (ESI): mass calculated for C14H11NO2, 225,08; found m/z 226,1 [M+H]+.

1H NMR (400 M is C, CD3OD): a 7.62 (m, 1H), 7,53 (m, 1H), 7,32 (m, 2H), 7,17 (d, J=8,5, 2H), 6.75 in (d, J=8,5, 2H), 4,18 (c, 2H).

B.2-[4-(2-Bromoethoxy)benzyl]benzoxazol

To a stirred solution of 4-benzoxazol-2-ylmethylene (5 g, of 22.2 mmol) in

CH3CN (100 ml) add Na2CO3(6.4 g, with 46.6 mmol) and dibromoethane (7.9 ml, and 88.8 mmol). The resulting suspension is heated to 70ºC for 72 h and filtered hot. The filtrate is concentrated under reduced pressure. The obtained solid is suspended in diethyl ether, filtered and the filtrate concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and purified on SiO2(110 g; CH2Cl2), receiving not quite white solid (1 g, the output of 13.7%). MS (ESI): mass calculated for C16H14BrNO2, 331,02; found m/z 332,0 [M+H]+.

1H NMR (400 MHz, CD3OD): a 7.62 (m, 1H), 7,53 (m, 1H), 7,34 (m, 2H), 7,29 (d, J=8,6, 2H), 6,92 (d, J=8,7, 2H), 4,28 (t, J=5,9, 2H), 4,23 (c, 2H), to 3.67 (t, J=5,9, 2H).

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

To a stirred solution of 2-[4-(2-bromoethoxy)benzyl]benzoxazole (0.5 g, 1.5 mmol) in CH3CN (7.5 ml) add utilizedabated (0.7 ml, 4.5 mmol). The mixture is stirred at room temperature for 48 h, then concentrated under reduced pressure. The resulting oil was dissolved in CH2Cl2and purified on SiO2(40 g; 0-25% acetone/CHsub> 2Cl2), receiving not quite white solid (275 mg, yield 45%). MS (ESI): mass calculated for C24H28N2O4, 408,20; found m/z 409,2 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.67 (m, 1H), 7,45 (m, 1H), 7,28 (d, J=9,0, 4H), to 6.88 (d, J=8,7, 2H), 4,20 (c, 2H), 4,12 (kV, J=7,1, 2H), 4,08 (t, J=5,9, 2H), 2,95 (d, 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) is heated at about 150ºc for 16 h and then cooled to room temperature. The obtained solid is crushed and dissolved in CH2Cl2(400 ml). The solution was washed with 1N. HCl (2×50 ml), then saturated aqueous NaHCO3(2×50 ml), dried, filtered and concentrated under reduced pressure. The residue is purified on SiO2(0-50% ethyl acetate/hexane), getting a white solid (10.5 g, yield 44%). MS (ESI): mass calculated for C14H11NOS, 241,06; found m/z 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 (d, J=8,3, 2H), 6,77 (d, J=8,6, 2H), 4,89 (c, 1H), 4,33 (c, 2H).

B.2-[4-(2-Bromoethoxy)benzyl]benzothiazole

To a stirred solution of 4-benzothiazol-2-ylmethylene (10.5 g, 43.5 m is ol) in CH 3CN (100 ml) add Cs2CO3(28,3 g, 87 mmol) and dibromoethane (18.7 ml, and 21.8 mmol). The resulting suspension is heated to 70ºC for 16 h, cooled to room temperature and then dissolved in CH2Cl2(400 ml). The solution was washed with H2About (2×50 ml), dried and concentrated. The resulting oil was dissolved in CH2Cl2and purified on SiO2(0-50% ethyl acetate/hexane), getting a white solid (7.5 g, yield 49.5 per cent). MS (ESI): mass calculated for C16H14BrNOS, 347,00; found m/z 348,1 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.99 (d, J=8,1, 1H), 7,79 (d, J=8,1, 1H), 7,45 (t, J=7,6, 1H), was 7.36-7,25 (m, 3H), 6.89 in (d, J=8,8, 2H), to 4.38 (c, 2H), 4,28 (t, J=6,3, 2H), 3,63 (t, J=6,3, 2H).

C.Methyl ether 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 CH3CN (20 ml) add methylisophthalic (0.7 ml, and 55.7 mmol) and N,N-diisopropylethylamine (1.5 ml, 8.6 mmol). The mixture is heated to 60ºC for 16 h, cooled to room temperature and then dissolved in CH2Cl2(100 ml). The solution was washed with H2About (2×20 ml), dried and concentrated. The resulting oil was dissolved in CH2Cl2and purified on SiO2(0-15% CH3OH/CH2Cl2), getting a white solid (1.1 g, yield 92%). MS (ESI): mass calculated for C23H26N2O3S, 410,17; found m/z 411, [M+H] +.

1H NMR (400 MHz, CDCl3): 7,98 (d, J=8,3, 1H), 7,76 (d, J=8,3, 1H), 7,42 (t, J=7,8, 1H), 7,33-7,24 (m, 3H), to 6.88 (d, J=8,8, 2H), 4,36 (c, 2H), 4,07 (t, J=6,1, 2H), 3,66 (c, 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

Salt triperoxonane acid 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 CH3CN (50 ml) is added hydrochloride ethyl ester 3-aminopropionic acid (3.4 g, 22 mmol) followed by addition of N,N-diisopropylethylamine (7.7 ml, 44 mmol). The mixture was stirred at 60ºC for 16 h, allow to cool to room temperature and then dissolved in CH2Cl2(100 ml). The resulting solution was washed with H2About (2×15 ml), dried, filtered and then concentrated under reduced pressure, obtaining a brown oil, which was used in the next stage.

B.Ethyl ester of 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) add Cs2CO3(10.8 g, 33 mmol) and 2-chlorobenzothiazole (2,72 ml, 22 mmol). The suspension is stirred at 100 the C during the night. The reaction mixture allow to cool to room temperature and then filtered through a layer of diatomaceous earth. The filtrate is concentrated under reduced pressure and purified on SiO2(100 g; 0-100% CH3OH/CH2Cl2)to give 1.9 g (yield 45%) of a light brown oil. MS (ESI): mass calculated for C22H22N2O4S, 386,13; found m/z 387,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,66 (d, J=8,1, 1H), 7,58 (d, J=8,3, 1H), 7,30 (d, J=7,8, 1H), 7,22-to 7.15 (m, 3H), 6,86 (d, 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 (t, J=6,6, 2H), 2,20 (users, 1H), 1,20 (t, J=7,1, 3H).

C.Ethyl ester 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]ethylamino}propionic acid (500 mg, 1,29 mmol) in CH3OH (15 ml) is added acetic acid (0,73 ml, 12.9 mmol), molecular sieves 3Å and [(1-amoxicilpin)oxy]trimethylsilane (of 1.55 ml, 7.7 mmol). Add cyanoborohydride sodium (365 mg, 5.8 mmol) and the mixture is heated at boiling temperature under reflux overnight. The mixture is cooled, filtered and concentrated. The residue is dissolved in CH2Cl2and the resulting solution was washed with saturated aqueous NaHCO3then with saturated salt solution, dried and concentrated. The obtained residue is purified on SiO2(40 g; 10-50% ethyl acetate/hexane),getting 374 mg (yield 68%) of colorless oil. MS (ESI): mass calculated for C23H26N2O4S, 426,16; found m/z 427,11 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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 (d, 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), of 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.Salt triperoxonane acid 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 CH3OH (5 ml) is added lithium hydroxide (80 mg, 3.3 mmol) in H2About (10 ml). The mixture is stirred at room temperature for 16 h and then concentrated under reduced pressure. The residue is dissolved in CH3OH and purified HPLC with reversed phase, getting mentioned in the title compound (391 mg, yield 92%). MS (ESI): mass calculated for C21H22N2O4S, 398,13; found m/z 399,1 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,73 (d, 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 (d, J=9,1, 2H), 5,17 (users, 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-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]benzothiazole

Specified in the header connection receive in accordance with the method of example 11, using the 1-(2-chloroethyl)pyrrolidine. MS (ESI): mass calculated for

With19H20N2O3, 324,15; found m/z 325,1 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.75 (d, J=8,1, 1H), 7,66 (d, J=8,0, 1H), 7,40 (dt, J=7,4, 1,3, 1H), 7,31-of 7.23 (m, 3H), 6,98 (d, J=6,8, 2H), 4,08 (t, J=6,3, 2H), only 2.91 (t, J=6,3, 2H), 2,67 (kV, J=7,2, 4H), 1,10 (t, J=7,2, 6H).

EXAMPLE 45

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

Specified in the header connection receive in accordance with the method of example 11, using hydrochloride (2-chloropropyl)dimethylamine. MS (ESI): mass calculated for C18H20N2O3, 312,15; found m/z 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 (d, J=7,9, 2H), 7.23 percent-to 7.18 (m, 2H), 6,91 (d, J=8,3, 2H), 4.09 to (users, 2H), 3,23 (users, 2H), 2,85 (users, 6H), 2,42 (users, 2H).

EXAMPLE 46

{2-[4-(Benzoxazol-2-ilaxi)phenoxy]ethyl}dimethylamine

Specified in the header connection receive in accordance with the method of example 11, using hydrochloride (2-chloroethyl)dimethylamine. MS (ESI): mass calculated for C17H18N2O3, 298,13; found m/z 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), of 4.05 (t, J=5,7, 2H), 2,72 (t, J=5,7, 2H), 2,32 (c, 6H).

EXAMPLE 47

2-[4-(2-Azepin-1 ylethoxy)phenoxy]benzoxazol

Specified in the header joint is receive in accordance with the method of example 11, using the hydrochloride of 1-(2-chloroethyl)azepane. MS (ESI): mass calculated for C21H24N2O3, 352,18; found m/z 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), equal to 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 header connection receive in accordance with the method of example 12, using hydrochloride (2-chloroethyl)dimethylamine and 2-chlorobenzothiazole. MS (ESI): mass calculated for C17H18N2O2S, 314,11; found m/z 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 (c, 6H).

EXAMPLE 49

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

Specified in the header connection receive in accordance with the method of example 12 using 1-(2-chloroethyl)pyrrolidine and 2-chlorobenzothiazole. MS (ESI): mass calculated for C19H20N2O2S, 340,12; found m/z 341,1 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (d, J=7,6, 1H), 7,66 (d, J=8,6, 1H), 7,41 (t, J=7,4, 1H), 7,32-7,25 (m, 3H), 7,00 (d, J=9,0, 2H), 4,16 (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}di is ethylamin

Specified in the header connection receive in accordance with the method of example 12, using hydrochloride (2-chloropropyl)dimethylamine and 2-chlorobenzothiazole. MS (ESI): mass calculated for C18H20N2O2S, 328,12; found m/z 329,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), to 7.64 (d, J=7,9, 1H), 7,37 (t, J=7,5, 1H), 7,31-7,20 (m, 3H), 6,92 (d, J=7,9, 2H), 4,11 (c, 2H), 3,25 (c, 2H), 2,85 (c, 6H), 2,43 (c, 2H).

EXAMPLE 51

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

Specified in the header connection receive in accordance with the method of example 12, using the hydrochloride of 1-(2-chloroethyl)azepane and 2-chlorobenzothiazole. MS (ESI): mass calculated for C21H24N2O2S, 368,16; found m/z 369,21 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.70 (d, J=7,5, 1H), 7,65 (d, J=7,9, 1H), 7,38-7,34 (m, 1H), 7,29-of 7.23 (m, 3H), 6,97 (userd, 2H), 4,59 (users, 2H), 3,64 (users, 2H), 3.46 in (users, 2H), 3,13 (users, 3H), 2,19 (users, 2H), 1,87 (users, 2H), 1,72 is 1.58 (m, 2H).

EXAMPLE 52

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

Specified in the header connection receive in accordance with the method of example 12, using the hydrochloride of 1-(2-chloroethyl)azepane and 2-chloro-6-methoxybenzothiazole. MS (ESI): mass calculated for C22H26N2O3S, 398,17; found m/z 399,2 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.75 (d, J=8,9, 1,H), 7,37-7,35 (m, 2), 7,26 (userd, 2H), 7,09-7,05 (m, 3H), 4,19 (t, J=6,1, 2H), 3,95 (c, 3H), is 3.08 (t, J=6,1, 2H), 2.91 in-2,88 (m, 4H), 1,76 (userd, 8H).

EXAMPLE 53

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

Specified in the header connection receive in accordance with the method of example 13 using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C26H26N2O4, 430,19; found m/z 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 (d, 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine

Specified in the header connection receive in accordance with the method of example 13, using cyclohexylethylamine. MS (ESI): mass calculated for C23H28N2O3, 380,21; found m/z 381,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=8,4, 1H), 7,42 (d, J=7,5, 1H), 7,35-to 7.18 (m, 4H), 6,97 (d, 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), equal to 1.82 (t, J=7,4, 4H), 1,64 (d, 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}benzoxazol

Specified in the header connection receive in accordance with the method of example 13 using 2-ethylpiperidine. MS (ESI): mass calculated for C22H26 N2O3, 366,19; found m/z 367,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=7,4, 1H), 7,42 (d, J=7,4, 1H), 7,31 (d, J=9,1, 2H), 7,30-7,20 (m, 2H), 6,97 (d, 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), to 0.92 (t, J=7,4, 3H).

EXAMPLE 56

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

Specified in the header connection receive in accordance with the method of example 13 using 4-phenylpiperidine-4-carbonitrile. MS (ESI): mass calculated for C27H25N3O5, 439,19; found m/z 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 (userd, 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}-4-phenylpiperidine-4-yl)alanon

Specified in the header connection receive in accordance with the method of example 13, using 1-(4-phenylpiperidine-4-yl)Etalon. MS (ESI): mass calculated for C28H28N2O4, 456,20; found m/z 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 (ushort, 2H), 2,17-2,05 (m, 2H), 1,92 (c, 3H).

EXAMPLE 58

2-{4-[2-4-Methylpiperidin-1-yl)ethoxy]phenoxy}benzoxazol

Specified in the header connection receive in accordance with the method of example 13 using 4-methylpiperidin. MS (ESI): mass calculated for C21H24N2O3, 352,18; found m/z 353,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50 (d, J=6,8, 1H), 7,42 (d, J=6,8, 1H), 7,31 (d, J=9,0, 2H), 7,30-7,20 (m, 2H), 6,97 (d, J=9,0, 2H), 4,13 (t, J=6,0, 2H), 2,97 (d, J=11,7, 2H), 2,80 (t, J=6,0, 2H), 2,11 (dt, J=11,7, J=2,2, 2H), 1,67 (c, 2H), 1,34 (users, 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol

Specified in the header connection receive in accordance with the method of example 13 using 4-(4-chlorophenyl)piperidine-4-ol. MS (ESI): mass calculated for C26H25ClN2O4, 464,15; found m/z 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 (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 (users, 1H).

EXAMPLE 60

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

Specified in the header connection receive in accordance with the method of example 13 using 4-(4-bromophenyl)piperidine-4-ol. MS (ESI): mass calculated for C26H25BrN2O4, 508,10; found m/z 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, H), 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 (users, 1H).

EXAMPLE 61

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

Specified in the header connection receive in accordance with the method of example 13 using 4-(4-chloro-3-triptoreline)piperidine-4-ol. MS (ESI): mass calculated for C27H24ClF3N2O4, 532,14; found m/z 533,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,89 (d, 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 (users, 1H).

EXAMPLE 62

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

Specified in the header connection receive in accordance with the method of example 13 using 4-benzylpiperidine-4-ol. MS (ESI): mass calculated for C27H28N2O4, 444,20; found m/z 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}cyclohexylethylamine

Specified in the header connection receive in accordance with the method of example 13, using Ziklag xidmetinin. MS (ESI): mass calculated for C22H26N2O3, 366,19; found m/z 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 (d, J=9,1, 2H), 7,35-7,25 (m, 2H), 7,03 (d, 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 (d, J=7,9, 4H), of 1.57 (d, J=12,2, 2H), 1.30 and of 1.12 (m, 4H), 1,10-1,00 (m, 1H).

EXAMPLE 64

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

Specified in the header connection receive in accordance with the method of example 13, using cyclopropanemethylamine. MS (ESI): mass calculated for C22H26N2O3, 366,19; found m/z 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=6,3, 2H), 1.60-to 1,50 (m, 2H), to 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}butylethylamine

Specified in the header connection receive in accordance with the method of example 13, using butylethylamine. MS (ESI): mass calculated for C21H26N2O3, 354,19; found m/z 355,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,41 (d, J=7,2, 1H), 7,32 (DD, J=7,3, 1,6, 1H), 7,22 (d, J=9,1, 1H), 7.18 in-7,10 (m, 2H), 6.87 in (d, J=9,1, 2H), was 4.02 (users, 2H), 2,85 (users, 2H), 2,61 (users, 2H), 2.49 USD (users, 2H), 1,42 (users, 2H), 1,31-1,19 (m, 2H), 1,05 (users, 3H), or 0.83 (t, J=7,3, 3H).

PRIMER

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

Specified in the header connection receive in accordance with the method of example 13, using benzylaminopurine. MS (ESI): mass calculated for

With24H24N2O4, 404,17; found m/z 405,2 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,46-7,37 (m, 3H), 7,33 (d, 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 (c, 2H), to 3.64 (t, J=6,2, 2H), 2,95 (d, J=5,8, 2H), was 2.76 (t, J=6,1, 2H).

EXAMPLE 67

2-{4-[2-(4-Benzylpiperidine-1-yl)ethoxy]phenoxy}benzoxazol

Specified in the header connection receive in accordance with the method of example 13 using 4-benzylpiperidine. MS (ESI): mass calculated for C27H28N2O3, 428,21; found m/z 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), by 2.55 (d, 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}piperidine-3-yl)methanol

Specified in the header connection receive in accordance with the method of example 13, using piperidine-3-ylmethanol. MS (ESI): mass calculated for C21H24N2O4, 368,17; found m/z 369,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,55-7,52 (m, 1H), of 7.48 to 7.4 (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 (userd, J=9,7, 1H), equal to 2.94 (t, J=5,6, 2H), 2,42 (t, J=9,1, 1H), to 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-(Benzoxazol-2-yloxy)phenoxy]ethyl}propylamino)ethanol

Specified in the header connection receive in accordance with the method of example 13 using 2-propylaminoethyl. MS (ESI): mass calculated for

With20H24N2O4, 356,17; found m/z 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 (d, J=9,1, 2H), 7,35-7,25 (m, 2H), 7,03 (d, 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), from 0.84 (t, J=7,3, 3H).

EXAMPLE 70

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

Specified in the header connection receive in accordance with the procedure of example 17 using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C26H26N2O3S, 446,17; found m/z 447,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,1, 1H), 7,66 (d, J=7,4, 1H), 7,54 (d, J=7,6, 2H), 7,42-7,35 (m, 3H), 7,33-7,22 (m, 4H), of 6.99 (d, J=9,0, 2H), 4,19 (t, J=5,8, 2H), 2,98-of 2.86 (m, 4H), to 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}cyclohexyl the ylamine

Specified in the header connection receive in accordance with the method of example 17, using cyclohexylethylamine. MS (ESI): mass calculated for C23H28N2O2S, 396,19; found m/z 397,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,1, 1H), 7,65 (d, 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), of 1.65 (d, 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 header connection receive in accordance with the procedure of example 17 using 4-(4-chlorophenyl)piperidine-4-ol. MS (ESI): mass calculated for C26H25ClN3O3S, 480,13; found m/z 481,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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), 1,79-1,74 (m, 2H), and 1.56 (users, 1H).

EXAMPLE 73

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

Specified in the header connection receive in accordance with the method of example 17, using dibutylamine. MS (ESI): mass calculated for C23H30N2O2S, 398,20; found m/z 399,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,63 (d, J=8,1, 1H), 7,55 (d, J=7,9, 1H), 7,28 (TT, J=7,7, 1,3, 1H), 7,20-7,13 (m, 3H), 6,85 (d, J=12,, 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 header connection receive in accordance with the procedure of example 17 using 4-(4-bromophenyl)piperidine-4-ol. MS (ESI): mass calculated for C26H25BrN2O3S, 524,08; found m/z 525,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (DD, J=8.0 a, 0,6, 1H), to 7.67 (DD, J=8.0 a, 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 2,14 (m, 2H), 1,76 (DD, J=14,22, 6, 2H), and 1.56 (users, 1H).

EXAMPLE 75

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

Specified in the header connection receive in accordance with the procedure of example 17 using 4-(4-chloro-3-triptoreline)piperidine-4-ol. MS (ESI): mass calculated for C27H24ClF3N2O3S, 548,11; found m/z 549,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,89 (d, 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 (users, 1H).

EXAMPLE 76

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

Specified in the header connection receive in accordance with the methodology in the EPA 17, using 4-benzylpiperidine-4-ol. MS (ESI): mass calculated for C27H28N2O3S, 460,18; found m/z 461,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), 7,66 (d, 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 (users, 1H).

EXAMPLE 77

2-[4-(2-Azetidin-1 ylethoxy)phenoxy]benzoxazol

Specified in the header connection receive in accordance with the method of example 21, using azetidin. MS (ESI): mass calculated for C18H18N2O3, 310,13; found m/z 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 (d, J=9,1, 2H), 7,32-7,24 (m, 2H), 7,00 (d, 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 (t, J=6,9, 2H).

EXAMPLE 78

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

Specified in the header connection receive in accordance with the method of example 22 using 2-phenyl-N-piperidine-4-ylacetamide and 2-chlorobenzoxazole. MS (ESI): mass calculated for C28H29N3O4, 471,22; found m/z 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 (userd, J=7,8, 1H), 4,10 (t, J=5,7, 2H), 3,90-of 3.80 (m, 1H), 3,60 (c, 2H), 2,89 (userd, J=11,5, 2H), of 2.81 (t, J=5,8, 2H), 2,28 (dt, J=11,6, 2,2, 2H), 1,92 (userid, J=12,6, 2,3, 2H), 1,46 to 1.37 (m, 2H).

EXAMPLE 79

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

Specified in the header connection receive in accordance with the method of example 22, using ethyl ether piperidine-3-carboxylic acid and 2-chlorobenzoxazole. MS (ESI): mass calculated for C23H26N2O5, 410,18; found m/z 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 (userd, J=8,2, 1H), 2,96-2,82 (m, 3H), 2,65 (TT, J=10,6, 3,7, 1H), is 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) of 1.30 (t, J=7,2, 3H).

EXAMPLE 80

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

Specified in the header connection receive in accordance with the method of example 22 using 4-piperidinylidene. MS (ESI): mass calculated for C25H31N3O2S, 437,21; found m/z 438,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (d, J=8,0, 1H), 7,69 (d, 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 (userd, J=11,7, 2H), 2,84 (t, J=6,0, 2H), 2.57 m (users, 2H), 2.40 a-2,30 m, 1H), 2,16 (dt, J=11,7, 1,6, 1H), 1,85 (userd, 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 header of the compounds is their gain in accordance with the method of example 17, using piperidine-4-ylmethanol. MS (ESI): mass calculated for C21H24N2O3S, 384,15; found m/z 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 in, 2,4, 2H), of 1.78 and 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 header connection receive in accordance with the method of example 22 using 2-phenyl-N-piperidine-4-ylacetamide. MS (ESI): mass calculated for C28H29N3O3S, 487,19; found m/z 488,2 [M+H]+.

1H NMR (400 MHz, CDCl3): for 7.78 (DD, J=8.0 a, 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 (d, J=7,9, 1H), 4,10 (t, J=5,8, 2H), 3,90-with 3.79 (m, 1H), 3,60 (c, 2H), 2,88 (d, 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 (d of q, J=11,1, 3,8, 2H).

EXAMPLE 83

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

Specified in the header connection receive in accordance with the method of example 22 using [1,4']bipyridinyl-2-it. MS (ESI): mass calculated for

With25H29N3O3S, 451,59; found m/z 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 (d, J=9,0, 2H), 4,35-to 4.15 (m, 1H), 4,10 (t, J=5,7, 2H), 3.15 in (t, J5,3, 2H), 3,00 (d, J=11,5, 2H), 2,71 (t, J=5,7, 2H), of 2.21 (t, J=6,5, 2H), 2,10 (t, J=11,5, 2H), 1,75-to 1.60 (m, 6H), USD 1.43 (d, J=10,0, 2H).

EXAMPLE 84

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

Specified in the header connection receive in accordance with the method of example 22 using 4-(2-piperazine-1-retil)morpholine. MS (ESI): mass calculated for C25H32N4O3S, 468,22; found m/z 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 (d, 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 (users, 16H).

EXAMPLE 85

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

Specified in the header connection receive in accordance with the method of example 32 using 4-(2-piperazine-1-retil)morpholine. MS (ESI): mass calculated for C25H32N4O2S, 452,22; found m/z 453,2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=8,0, 1H), 7,68 (d, J=8,0, 1H), 7,45-7,30 (m, 6H), of 3.54 (t, J=4,5, 4H), to 2.75 (t, J=8,3, 4H), 2,50-2,20 (users, 16H).

EXAMPLE 86

2-{4-[3-(4-Phenylpiperazin-1-yl)propoxy]phenoxy}benzoxazol

Specified in the header connection receive in accordance with the method of example 27 using 4-phenylpiperidine. MS (ESI): mass calculated for C27H28N2O3, 428,21; found m/z 4292 [M+H] +.

1H NMR (400 MHz, CD3OD): 7,40-7,38 (m, 1H), 7,34-7,32 (m, 1H), 7,24 (d, J=9,1, 2H), 7,22 for 7.12 (m, 4H), 7,07 (t, J=7,0, 1H), 6,94 (d, J=9,1, 2H), 3,99 (t, J=6,1, 2H), 3,06 (d, J=11,7, 2H), 2.57 m (t, J=7,6, 2H), 2.49 USD (m, 1H), 2,13 (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 header connection receive in accordance with the method of example 27 using 2-chlorobenzothiazole. MS (ESI): mass calculated for C27H28N2O3S, 460,18; found m/z 461,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,65 (d, J=7,8, 1H), 7,53 (d, 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), is 1.81 (d, J=12,3, 2H).

EXAMPLE 88

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

Specified in the header connection receive in accordance with the method of example 29 using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C26H26N2O3, 414,51; found m/z 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 (users, 1H).

EXAMPLE 89

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

Specified in the header connection receive in accordance with metadisciplinary 29, using cyclohexylethylamine. MS (ESI): mass calculated for C23H28N2O2, 364,22; found m/z 365,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=7,8, 1H), 7,41 (d, 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), 1,08 (t, J=7,0, 4H).

EXAMPLE 90

2-[4-(2-Pyrrolidin-1-retil)phenoxy]benzoxazol

Specified in the header connection receive in accordance with the method of example 29, using pyrrolidine. MS (ESI): mass calculated for C19H20N2O2, 308,15; found m/z 309,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=7,6, 1H), 7,42 (d, 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]benzoxazol

Specified in the header connection receive in accordance with the method of example 29, using ASEAN. MS (ESI): mass calculated for C21H24N2O2, 336,18; found m/z sauce 337,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50 (d, J=7,6, 1H), 7,39 (d, 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-(Benzoxazol-2-yloxy)phenyl]ethyl}cyclopropanemethylamine

Specified in the header connection receive in accordance with the method of example 29, using qi is coproporphyrin. MS (ESI): mass calculated for C22H26N2O2, 350,20; found m/z 351,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50 (d, J=7,6, 1H), 7,39 (d, 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 (d, J=6,5, 2H), 1.56 to the 1.44 (m, 2H), of 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-(Benzoxazol-2-yloxy)phenyl]ethyl}dibutylamine

Specified in the header connection receive in accordance with the method of example 29, using dibutylamine. MS (ESI): mass calculated for C23H30N2O2, 366,23; found m/z 367,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=7,4, 1H), 7,39 (d, 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-(Benzoxazol-2-yloxy)phenyl]ethyl}piperidine-4-ol

Specified in the header connection receive in accordance with the method of example 29 using 4-hydroxypiperidine. MS (ESI): mass calculated for C20H22N2O3, 338,16; found m/z 339,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50 (d, J=7,6, 1H), 7,39 (d, J=7,6, 1H), 7,34-7,16 (m, 6H), 3.72 points-3,63 (m, 1H), 3,29 (users, 1H), 2.91 in-2,78 (m, 4H), 2,63-of 2.56 (m, 2H), of 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-ol

Specified in the header of the receive in connection with the compliance with the procedure of example 30, using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C26H26N2O3S, 430,57; found m/z 431,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76-7,74 (m, 1H), to 7.67 (DD, J=8.0 a, 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 (osirm, 2H).

EXAMPLE 96

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

Specified in the header connection receive in accordance with the method of example 29, using methyl ether piperidine-4-carboxylic acid. MS (ESI): mass calculated for C22H24N2O4, 380,17; found m/z 381,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,50 (d, J=8,1, 1H), 7,39 (d, J=8,1, 1H), 7,34-7,16 (m, 6H), 3,67 (c, 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), 1,84-1,73 (m, 2H).

EXAMPLE 97

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

Specified in the header connection receive in accordance with the method of example 30, using pyrrolidine. MS (ESI): mass calculated for C19H20N2OS, 324,13; found m/z 325,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,0, 1H), 7,65 (d, 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)Fe is hydroxy]benzothiazole

Specified in the header connection receive in accordance with the method of example 30, using ASEAN. MS (ESI): mass calculated for C21H24N2OS, 352,16; found m/z 353,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,0, 1H), 7,65 (d, 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 header connection receive in accordance with the method of example 30, using cyclopropanemethylamine. MS (ESI): mass calculated for C22H26N2OS, 366,18; found m/z 367,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,6, 1H), 7,65 (d, J=8,2, 1H), 7,38 (t, J=8,6, 1H), 7,30-7,22 (m, 5H), 2,87 was 2.76 (m, 4H), to 2.57 (t, J=7,6, 2H), 2,44 (d, J=6,5, 2H), 1.56 to a 1.45 (m, 2H), of 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 header connection receive in accordance with the method of example 30, using dibutylamine. MS (ESI): mass calculated for C23H30N2OS, 382,21; found m/z 383,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,2, 1H), 7,65 (d, 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)pheno is si]benzothiazole

Specified in the header connection receive in accordance with the method of example 30, using piperidine. MS (ESI): mass calculated for C20H22N2OS, 338,48; found m/z 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 header connection receive in accordance with the method of example 30, using 4-hydroxypiperidine. MS (ESI): mass calculated for C20H22N2O2S, 354,14; found m/z 355,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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 (users, 1H), 2,65 is 2.55 (m, 2H), of 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 header connection receive in accordance with the method of example 30, using methyl ether piperidine-4-carboxylic acid. MS (ESI): mass calculated for C22H24N2O3S, 396,15; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,3, 1H), 7,66 (d, J=8,3, 1H), 7,38 (t, J=8,3, 1H), 7,29-of 7.23 (m, 5H), 3,69 (c, 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-at 1.91 (m, 2), 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 header connection receive in accordance with the method of example 31 using amide piperidine-4-carboxylic acid. MS (ESI): mass calculated for C21H23N3O2S, 381,15; found m/z 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 (userd, J=26,0, 1H), 3,09 (userd, 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 (t, J=11,4, 2H), 1,98 (userd, J=11,2, 2H), 1,87-to 1.77 (m, 2H).

EXAMPLE 105

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

Specified in the header connection receive in accordance with the method of example 31, using ethyl ether piperidine-3-carboxylic acid. MS (ESI): mass calculated for C23H26N2O3S, 410,17; found m/z 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 (userd, 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 and (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) of 1.30 (t, J=7,2, 3H).

EXAMPLE 106

Ethyl ester of 1-{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}-4-phenylpiperidine-4-carboxylic KIS is the notes

Specified in the header connection receive in accordance with the method of example 31, using the ethyl ester of 4-phenylpiperidine-4-carboxylic acid. MS (ESI): mass calculated for C29H30N2O3S, 486,20; found m/z 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 (userd, 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

Specified in the header connection receive in accordance with the method of example 31, using ethyl ether piperidine-4-luxusni acid. MS (ESI): mass calculated for C24H28N2O3S, 424,18; found m/z 425,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, 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 (d, 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 (d, 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 header connection receive in accordance with the method of example 31 using 1-piperidine-4-yl-1,3-dihydroindol-2-it. MS (ESI): mass calculated for C28H27N3O2S, 469,18; naude what about the m/z 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 (c, 2H), 3,36 (userd, 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 header connection receive in accordance with the method of example 31 using 1-piperidine-4-iparralde-2-it. MS (ESI): mass calculated for C24H27N3O2S, 421,18; found m/z 422,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, J=8,0, 1H), 7,69 (DD, J=8.0 a, 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 (userd, 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 header connection receive in accordance with the method of example 31 using 2-phenyl-N-piperidine-4-ylacetamide. MS (ESI): mass calculated for C28H29N3O2S, 471,20; found m/z 472,5 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (DD, J=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 (userd, J=7,9, 1H), 3,93-3,82 (m, 1H), 3,60 (c, 2H), 2,93 (userd, 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-diazaspiro[4.5]Decan-1-he

Specified in the header connection receive in accordance with the method of example 31 using 2,8-diazaspiro[4,5]Decan-1-it. MS (ESI): mass calculated for C23H25N3O2S, 407,17; found m/z 408,4 [M+H]+.

1H NMR (400 MHz, CDCl3): for 7.78 (d, 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 (users, 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 (userd, J=13,1, 2H).

EXAMPLE 112

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

Specified in the header connection receive in accordance with the method of example 31 using 3-hydroxypiperidine. MS (ESI): mass calculated for C20H22N2O2S, 354,14; found m/z 355,3 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (d, J=7,6, 1H), of 7.70 (DD, J=8.0 a, 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), 1,92-1,80 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 header connection receive in accordance with the method of example 31, using ethyl ether piperidine-3-carb is the new acid. MS (ESI): mass calculated for C23H26N2O3S, 410,17; found m/z 411,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (d, J=8,0, 1H), 7,69 (DD, J=7,9, 0,7, 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 (userd, 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), of 1.30 (t, J=7,3, 3H).

EXAMPLE 114

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

Specified in the header connection receive in accordance with the method of example 31 using 4-piperidinylidene. MS (ESI): mass calculated for C25H31N3OS, 421,22; found m/z 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 (userd, 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 of 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 header connection receive in accordance with the method of example 32, using 1-methylpiperazine. MS (ESI): mass calculated for C20H23N3OS, 353,16; found m/z 354,1 [M+H]+.

1H NMR (400 MHz, CD3OD): to 7.77 (6, J=8,01, 1H), to 7.64 (d, J=8,1, 1H), 7,41 (t, J=8,2, 1H), 7,37 (d, 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 (c, 3H).

EXAMPLE 116

1-{3-[4-(Benzoxazol-2-ylox is)phenyl]propyl}-4-phenylpiperidine-4-ol

Specified in the header connection receive in accordance with the method of example 35 using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C27H28N2O3, 428,21; found m/z 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), 4,76 (c, 1H), 2,66 (t, J=7,6, 4H), of 2.45 (m, 4H), of 1.92 (t, J=7,1, 2H), 1,78 (t, J=7,1, 2H), 1,58 (d, J=12,3, 2H).

EXAMPLE 117

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

Specified in the header connection receive in accordance with the method of example 37 using 4-(4-bromophenyl)piperidine-4-ol. MS (ESI): mass calculated for C26H26BrN3O3, 507,12; found m/z 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-Benzimidazole-2-yloxy)phenoxy]ethyl}-4-(4-chlorophenyl)piperidine-4-ol

Specified in the header connection receive in accordance with the method of example 37 using 4-(4-chlorophenyl)piperidine-4-ol. MS (ESI): mass calculated for C26H26ClN3O3, 463,17; found m/z 464,2 [M+H]+.

1H NMR (400 MHz, 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-Benzimidazole-2-yloxy)phenoxy]ethyl}-4-benzylpiperidine-4-ol

Specified in the header connection receive in accordance with the method of example 37 using 4-benzylpiperidine-4-ol. MS (ESI): mass calculated for C27H29N3O3, 443,22; found m/z 444,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,53 (users, 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]benzoxazol

Specified in the header connection receive in accordance with the method of example 35, using piperidine. MS (ESI): mass calculated for C21H24N2O2, 336,18; found m/z 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 (c, 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-(Benzoxazol-2-yloxy)phenyl]propyl}dibutylamine

Specified in the header connection receive in accordance with the method of example 35, using dibutylamine. MS (ESI): mass calculated for C24H32N2O2, 380,25; found m/z 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 (d, 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), ,40-1,20 (m, 8H), to 0.88 (t, J=7,1, 6H).

EXAMPLE 122

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

Specified in the header connection receive in accordance with the method of example 35, using cyclopropanemethylamine. MS (ESI): mass calculated for C23H28N2O2, 364,22; found m/z 365,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,63 (d, J=8,6, 1H), 7,40 (d, J=8,6, 1H), 7,32 (d, 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 (d, 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 (d, J=4,2, 2H), 0,05 (d, J=4,8, 2H).

EXAMPLE 123

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

Specified in the header connection receive in accordance with the method of example 38, using cyclohexylethylamine. MS (ESI): mass calculated for C23H29N3O, 363,23; found m/z 364,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,44 (users, 1H), 7,43-7,33 (m, 2H), 7,13-7,05 (m, 6H), 3,17 (t, J=11,7, 1H), 3,10 (66, J=7,0, 7,0, 2H), 2,99-and 2.83 (m, 4H), to 2.06 (d, J=9,8, 2H), 1,89 (d, J=12,5, 2H), 1.69 in (d, 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-benzimidazole

Specified in the header connection receive in accordance with the method of example 38, using pyrrolidine. MS (ESI): mass calculated for C19H21N3O, 307,17; ideno m/z 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-benzimidazole

Specified in the header connection receive in accordance with the method of example 38, using ASEAN. MS (ESI): mass calculated for C21H25N3O, 335,20; found m/z 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-Benzimidazole-2-yloxy)phenyl]ethyl}dibutylamine

Specified in the header connection receive in accordance with the method of example 38, using dibutylamine. MS (ESI): mass calculated for C23H31N3O, 365,25; found m/z 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-Benzimidazole-2-yloxy)phenyl]ethyl}piperidine-4-ol

Specified in the header connection receive in accordance with the procedure of example 38 using 4-hydroxypiperidine. MS (ESI): mass calculated for C20H23N3O2, 337,18; found m/z 338,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,70 (users, 1H), 7,50-7,44 (m, 1H), 7,33-7,27 (who, 1H), 7,24 (users, 4H), 7,14-7,07 (m, 2H), 3,93 (users, 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-benzimidazole-2-yloxy)phenyl]ethyl}piperidine-4-carboxylic acid

Specified in the header connection receive in accordance with the method of example 38, using methyl ether piperidine-4-carboxylic acid. MS (ESI): mass calculated for C22H25N3O3, 379,19; found m/z 380,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,76 (users, 1H), 7,50-7,44 (m, 1H), 7.24 to 7,06 (m, 7H), 3,68 (c, 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, J=11,1, 2H), 1,98-1,90 (m, 2H), 1,86-of 1.74 (m, 2H).

EXAMPLE 129

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

Specified in the header connection receive in accordance with the method of example 37, using cyclohexylethylamine. MS (ESI): mass calculated for C23H29N3O2, 379,23; found m/z 380,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,23 (c, 1H), 7,34-7,25 (m, 4H), 7,07 (d, J=3,5, 2H), 6,98 (d, J=9,0, 2H), 3,94 (t, J=6,4, 2H), 2,80 (t, J=6,4, 2H), 2.57 m (d, J=7,1, 2H), 2,50 (c, 2H), 1,72 (d, J=7,8, 2H), 1.55V (c, 1H), 1,20 (t, J=9,0, 4H), 0,99 (t, J=7,1, 3H).

EXAMPLE 130

2-{4-[2-(4-Methylpiperidin-1-yl)ethoxy]phenoxy}-1H-benzimidazole

Specified in the header connection receive according the method of example 35, using 4-methylpiperidin. MS (ESI): mass calculated for C21H25N3O2, 351,19; found m/z 352,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,30 (c, 1H), 7,34-7,25 (m, 4H), was 7.08 (d, J=3,8, 2H), 6,99 (d, J=9,0, 2H), 4,08 (t, J=5,8, 2H), 2,89 (d, J=11,4, 2H), to 2.67 (t, J=5,8, 2H), 2,00 (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), from 0.88 (d, J=6,4, 3H).

EXAMPLE 131

2-{4-[2-(2-Ethylpiperidine-1-yl)ethoxy]phenoxy}-1H-benzimidazole

Specified in the header connection receive in accordance with the method of example 37 using 2-ethylpiperidine. MS (ESI): mass calculated for C22H27N3O2, 365,21; found m/z 366,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to 12.28 (c, 1H), 7,32-7,25 (m, 4H), was 7.08 (d, J=3,8, 2H), 6,99 (d, J=8,4, 2H), of 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), from 0.84 (t, J=7,5, 3H).

EXAMPLE 132

2-[4-(2-piperidine-1-ylethoxy)phenoxy]-1H-benzimidazole

Specified in the header connection receive in accordance with the method of example 37, using piperidine. MS (ESI): mass calculated for C20H23N3O2, 337,18; found m/z 338,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,25 (users, 1H), 7,35-7,25 (m, 4H), 7,10-7,00 (m, 2H), 6,99 (d, J=9,0, 2H), 4,07 (t, J=5,9, 2H), and 2.79 (t, J=5,9, 2H), 2,43 (c, 4H), 1,55-of 1.45 (m, 4H), 1,38 (c, 2H).

EXAMPLE 133

(1-{2-[4-(1H-Benzimidazole-2-yloxy)the dryer is XI]ethyl}piperidine-4-yl)methanol

Specified in the header connection receive in accordance with the method of example 35, using piperidine-4-ylmethanol. MS (ESI): mass calculated for C21H25N3O3, 367,19; found m/z 368,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,24 (c, 1H), 7,35-7,25 (m, 4H), 7,01 (c, 2H), 6,99 (d, J=7,1, 2H), 4,40 (c, 1H), 4,10 (t, J=5,7, 2H), 3,25 (t, J=5,4, 2H), 2,93 (d, J=11,1, 2H), to 2.67 (t, J=5,6, 2H), 1,98 (t, J=11,6, 2H), 1,63 (d, J=11,6, 2H), 1.28 (in c, 1H), 1,12 (d, J=9,1, 2H).

EXAMPLE 134

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

Specified in the header connection receive in accordance with the method of example 37 using 4-hydroxypiperidine. MS (ESI): mass calculated for C20H23N3O3, 353,17; found m/z 354,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,24 (c, 1H), 7,35-7,25 (m, 4H), 7,07 (d, J=9,0, 2H), 6,99 (d, J=9,0, 2H), 4,40 (c, 1H), 4,08 (t, J=5,8, 2H), 2,53 (c, 1H), 2,78 (d, J=11,2, 2H), 2,66 (t, J=5,8, 2H), 2,12 (t, J=10,3, 2H), 1,70 (d, J=9,1,21-1), to 1.38 (d, J=9,9, 2H).

EXAMPLE 135

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

Specified in the header connection receive in accordance with the method of example 40, using pyrrolidine. MS (ESI): mass calculated for C20H22N2O4, 354,16; found m/z 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 (d, J=9,1, 2H), 7,35-7,25 (m, 2H), 7,03 (d, J=9,1, 2H), 4,91 (d, 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), 1,68 (c, 4H).

EXAMPLE 136

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

Specified in the header connection receive in accordance with the method of example 41, using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C27H28N2O3, 428,21; found m/z 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 (d, J=8,6, 2H), 4,20 (c, 2H), 4,13 (t, J=5,5, 2H), 2,87 (m, 4H), to 2.66 (t, J=11,4, 2H), 2,13 (dt, J=12,8, 3,6, 2H), 1,72 (d, J=12,6, 2H).

EXAMPLE 137

Amide 1-[2-(4-Benzoxazol-2-ylmethylene)ethyl]piperidine-4-carboxylic acid

Specified in the header connection receive in accordance with the method of example 41, using amide piperidine-4-carboxylic acid. MS (ESI): mass calculated for C22H25N3O3, 379,19; found m/z 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 (d, J=8,7, 2H), 6,92 (d, J=8,7, 2H), 4,22 (c, 2H), 4,11 (t, J=5,6, 2H), of 3.07 (d, 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

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

Specified in the header connection receive in accordance with the method of EXAMPLE 11, stage a and b, and example 37, steps In and using the hydrochloride of 1-(2-chloroethylamine. MS (ESI): mass calculated for C21H25N3O2, 351,19; found m/z 352,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to 12.28 (c, 1H), 7,35-7,25 (m, 4H), 7,07 (d, J=9,1, 2H), 7,00 (d, J=9,1, 2H), of 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-Benzimidazole-2-yloxy)phenoxy]propyl}dimethylamine

Specified in the header connection receive in accordance with the method of example 11, stage a and b, and example 37, steps In and using hydrochloride (2-chloropropyl)dimethylamine. MS (ESI): mass calculated for C18H21N3O2, 311,16; found m/z 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 (c, 6H) 2,02-of 1.95 (m, 2H).

EXAMPLE 140

2-[4-(2-Pyrrolidin-1 ylethoxy)phenoxy]-1H-benzimidazole

Specified in the header connection receive in accordance with the method of example 21, stages a and b, and example 35, steps In and using pyrrolidine. MS (ESI): mass calculated for C19H21N3O2, 323,16; found m/z 324,2 [M+H]+.

1H NMR(400 MHz, CDCl3): 7,27 (users, 2H), 7,15 (d, 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 (users, 4H), 1,92 (users, 4H).

EXAMPLE 141

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

Specified in the header of the who begins to receive in accordance with the method of example 21, stages a and b, and example 35, steps In and using diethylamine. MS (ESI): mass calculated for C19H23N3O2, 325,18; found m/z 326,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,29 (users, 2H), 7,18 (d, J=9,0, 2H), 7,10-7,05 (m, 2H), 6,98 (d, J=9,0, 2H), a 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-ylethoxy)phenoxy]-1H-benzimidazole

Specified in the header connection receive in accordance with the method of example 21, stages a and b, and example, stages b and C, using morpholine. MS (ESI): mass calculated for C19H21N3O3, 339,16; found m/z 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 (d, 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 according to this invention, which are given in the present description, but for which there is no direct description of receipt can be obtained by methods similar to those described in the present description, in the light of the knowledge of the person skilled in the art and in accordance with the instructions provided in this description. For example, derivatives of benzothiazole, represented by reference numbers 143-202 and 204-229, can be obtained by methods similar to those described for related compounds.

EXAMPLE 203

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

Specified in the header connection receive in accordance with the methods of example 20 and example 18, using the hydrochloride of the ethyl ester sarcosine. MS (ESI): mass calculated for C24H27N3O5S, 469,56; found m/z 470,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,02, 1H), 7,65 (d, 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 (users, 2H), 3.45 points-of 3.54 (m, 3H), 3,35 (users, 1H), 3,25 (users, 1H), 3,12 (c, 2H), 2,96 (c, 1H), was 2.76 (users, 2H), 1,92-of 2.08 (m, 4H).

EXAMPLES 230-231 and 485

As indicated in the context of this description, the compounds of this invention are described in the present description, but for which there is no direct description of their receipt, may be obtained by methods similar to those described in the present description, in the light of the knowledge of the person skilled in the art and in accordance with the instructions provided in this description. For example, benzimidazole derivatives represented by the reference rooms 230-231 and 485 can be obtained by methods similar to those described for related compounds.

EXAMPLE 250

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

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

A mixture of 4-benzyloxy is singleride (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) is stirred at the boiling point under reflux for 20 hours, the Reaction mixture was cooled to room temperature and filtered. The solvent is removed under reduced pressure, getting a clear Golden oil. The resulting oil was diluted with iPrOH (100 ml) and the mixture filtered. The solid is dried in the air, getting a white solid (19.7 g, yield 85%). TLC (SiO215% acetone/CH2Cl2): Rf=0,32. MS (ESI): mass calculated for C22H27NO3, 353,2; found m/z 354,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,44 (d, J=7,1, 2H), 7,39 (t, J=7,1, 2H), 7,33 (d, J=7,2, 1H), 7,18 (d, J=8,2, 2H), 6,94 (2H, J=8,6, 2H), 5,08 (c, 2H), Android 4.04 (q, J=7,09, 2H), 2,72 (d, J=11,5, 2H), 2,32-to 2.18 (m, 1H), 1,94 (t, J=11,6, 2H), 1,76 (d, J=10,2, 2H), 1,59 is 1.48 (m, 2H), 1,17 (t, J=7,1, 3H).

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

Ethyl ester of 1-(4-benzyloxybenzyl)piperidine-4-carboxylic acid (10.0 g, 28.3 mmol) dissolved in a mixture of 1:1 ethanol/ethyl acetate (150 ml). To the resulting solution was added Pd on carbon (10 wt.%, 503 mg) in the form of a suspension in ethanol (5.0 ml). The resulting suspension is placed in hydrogenator Parra at a pressure of H240 lb/in2and subjected to shaking during the night. The reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure, getting a clear Golden oil. The oil is purified on SiO2(90 g; 50% acetone/CH2Cl2)to give white solid (2.0 g, yield 27%). TLC (SiO2, 50% acetone/CH2Cl2): Rf=0,32. MS (ESI): mass calculated for C15H21NO3, 263,2; found m/z AZN 264.2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 9,25 (c, 1H), 7,05 (d, J=8,4, 2H), of 6.68 (d, J=8,4, 2H), Android 4.04 (q, J=7,1, 2H), 3,34 (c, 2H), 2,71 (d, J=11,5, 2H), 2,32-to 2.18 (m, 1H), 1,92 (t, J=11,6, 2H), 1,76 (d, J=10,2, 2H), 1,59 is 1.48 (m, 2H), of 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 CH3CN (15 ml) add K2CO3(564 mg, 4.1 mmol) and 2-chlorobenzothiazole (0,50 ml, 4.0 mmol). The suspension is heated to 80ºC and stirred over night. The reaction mixture allow to cool to room temperature and then filtered through a layer of diatomaceous earth. The filtrate is concentrated under reduced pressure and the residue purified on SiO2(12 g; 0-15% acetone/CH2Cl2), receiving transparent colorless sticky oil (717 mg, yield 94%). TLC (SiO215% acetone/CH2Cl2): Rf=0,5. MS (ESI): mass calculated for C22H24N2O3S, 396,2; found m/z 397,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=8,0, 1H), 7,68 (d, 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 (c, 2H), was 2.76 (d, J=11,5, 2H), 2,34-2,22 (m, 1H), 2,02 (t, J=11,6, 2H), 1,80 (d, J=10,2, 2H), 1,64-and 1.54 (m, 2H), of 1.18 (t, J=7,1, 3H).

D.1-[4-(Benzothiazol-2-yloxy)benzyl]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) add potassium hydroxide (206 mg, 3.1 mmol). The reaction mixture was stirred at room temperature for 20 h and the solution treated with 1M HCl to pH 5.5. The resulting solution was extracted with 10% iPrOH/CHCl3(3×50 ml). The combined extracts dried (MgSO4), filtered and concentrated under reduced pressure, obtaining white solid (561 mg, yield 91%). MS (ESI): mass calculated for C20H20N2O3S, 368,1; found m/z 369,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=7,6, 1H), 7,69 (d, J=7,6, 1H), of 7.48-7,34 (m, 5H), 7,33 (t, J=7,1, 1H), 3,49 (c, 2H), was 2.76 (d, J=11,4, 2H), 2,22-2,11 (m, 1H), 2,02 (t, J=11,2, 2H), 1,80 (d, J=13,2, 2H), 1,62 is 1.48 (m, 2H,), of 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) add Cs2CO3(5.5 g, and 17.2 mmol). The reaction mixture was stirred at 60ºC for 24 hours of the mixture of the OHL who promote to room temperature, filtered through a layer of diatomaceous earth and concentrated under reduced pressure, obtaining the crude product as an orange oil. The oil is triturated in a mixture of hexane/CH2Cl2(100 ml), the layer of the solvent is decanted and the residue concentrated under reduced pressure, obtaining an orange oil which is further purified on SiO2(120 g; 0-50% ethyl acetate/hexane)to give white solid (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).

B.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 mmol) and molecular sieves (500 mg, crushed, 4Å) in ClCH2CH2Cl (10 ml) was stirred at room temperature for 1 h To the obtained mixture is added NaBH(OAc)3(830 mg, to 3.92 mmol). The mixture is stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(50 ml) and concentrate under reduced pressure, obtaining the crude product as a yellow oil. The crude product is purified on SiO2(40 g; 0-100% acetone/CH2Cl2), getting a clear oil, which crystallized upon standing (287 mg, yield 36%). MS (ESI): mass, is ycycline for C 23H25N3O2S, of 407.5; found m/z 408,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, J=8,0, 1H), 7,69 (d, J=8,0, 1H), 7,41-7,30 (m, 3H), 7,35-7,27 (m, 3H), 4,46-3,98 (m, 1H), 3,71 (c, 2H), 3,36 (t, J=6,9, 2H), 2,97 (d, 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 EDCl (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 layers are combined, dried (MgSO4) and concentrated under reduced pressure, getting a clear Golden oil. The oil is purified on SiO2(120 g; 0-10% acetone/CH2Cl2)to give white solid (2.4 g, yield 34%). TLC (SiO215% acetone/CH2Cl2): Rf=0,35. MS (ESI): mass calculated for C12H14FNO2, 223,1; found m/z 224,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 10,26 (c, 1H), 7,18 (d, J=11,6, 1H), 7,00, (d, J=8,3, 1H), 6,98 (t, J=8,5, 1H), 3,42 (users, 4H), 1,65-of 1.45 (m, 6H).

B.2-Fluoro-4-piperidine-1-ylmethylene

The solution sociallyengaged (1.9 g, 50 mmol) in THF (40 ml) was stirred at 5ºC. To the mixture (3-fluoro-4-hydroxyphenyl)piperidine-1-ylmethanone (2.3 g, 1.4 mmol) in THF (10 ml) for 15 min and then the mixture is heated to 60ºC. After 20 h the mixture is cooled to 5ºC and add saturated NH4Cl (200 ml) followed by addition of CH2Cl2(200 ml). The organic layer is separated, dried (MgSO4) and concentrated under reduced pressure, obtaining white solid (812 mg, yield 37%). TLC (SiO2, acetone): Rf=0,22. MS (ESI): mass calculated for C12H16FNO, 209,1; found m/z 210,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to 6.58 (d, J=13,4, 1H), 6.48 in (d, J=8,2, 1H), 6,40 (t, J=9,9, 1H), 3,14 (c, 2H), 2,24 (users, 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 CH3CN (10 ml) add K2CO3(201 mg, 1.5 mmol) and 2-chlorobenzothiazole (of 0.14 ml, 1.1 mmol). The suspension is heated to 80ºC and stirred over night. The reaction mixture allow to cool to room temperature and then filtered through a layer of diatomaceous earth. The filtrate is concentrated under reduced pressure and the residue purified on SiO2(12 g; 0-50% acetone/CH2Cl2), getting a clear Golden oil (142 mg, yield 57%). TLC (SiO2, 50% acetone/CH2Cl2): Rf=0,44. MS (ESI): mass calculated for C19H19FN2OS, 342,1; found m/z 343,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): of 7.95 (d, J=7,9, 1H), 7,69 (d, J=7,5, 1H), 7,56 (t, J=8,2, 1H), 7,47-to 7.32 (m, 3H), 7,44 (d, J=15,4, 1H), 3,48 (c, 2H), 2,36 (c, 4H), 1,631,37 (m, 6H).

EXAMPLE 253

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

A.tert-Butyl ether ({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

A mixture of 4-(benzothiazol-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 ClCH2CH2Cl (10 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture portions added NaBH(OAc)3within 1.5 h (4×207 mg, 3.9 mmol). The resulting 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 NaHCO3(1×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a pale yellow oil. The crude product is purified on SiO2(40 g; 0-5% 2M NH3in CH3OH/CH2Cl2)to give a white foam (504 mg, yield 59%). MS (ESI): mass calculated for C24H29N3O3S, 439,6; found m/z 440,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (users, 1H), 3,50 (c, 2H), 2,82 was 2.76 (m, 2H), 2,16-to 2.06 (m, 2H), 1,96-of 1.88 (m, 2H), 1,45 (c, 9H), 1,48-to 1.38 (m, 2H).

B.1-[4-(Ben is thiazol-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 0ºC added dropwise 4n. HCl in dioxane (1.8 ml, 7.2 mmol). The resulting reaction mixture was stirred at room temperature for 2 hours produce the Desired product by filtration and washed with Et2O (50 ml)to give a white powder (187 mg, yield 100%). MS (ESI): mass calculated for C19H21N3OS, 339,5; found m/z 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 in (c, 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 add TEA (to 0.70 ml, 5.0 mmol) followed by the addition of acetoacetanilide (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 NaHCO3(1×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. Neojidanni the product purified on SiO 2(40 g; 0-10% CH3OH/CH2Cl2)to give white solid (410 mg, yield 93%). MS (ESI): mass calculated for C23H25N3O4S, 439,2; found m/z 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, (c, 2H), 3,93-3,82 (m, 1H), 3,50 (c, 2H), and 2.83 (d, J=11,9, 2H), 2,15 (c, 3H), and 2.14 (t, J=11,9, 2H), 1,93 (d, 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), CH3OH (10 ml) and H2About (10 ml) is added lithium hydroxide (an 80.2 mg, to 3.34 mmol). The resulting mixture was stirred at room temperature overnight. The mixture is extracted with CH2Cl2(30 ml×3). The combined organic phases are concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2)to give white solid (297 mg, yield 82%). MS (ESI): mass calculated for C21H23N3O3S, 397,2; found m/z 398,3 [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), 7,31-of 7.23 (m, 3H), 6,83 (d, J=8,1, 1H), 5,33 (users, 1H), 3,99 (c, 2H), a 3.87 of 3.75 (m, 1H), 3,50 (c, 2H), 2,85 (d, J=11,4, 2H), and 2.14 (t, J=10,9, 2H), 1,92 (d, J=12,6, 2H), 1.56 to USD 1.43 (m, 2H).

P the EMER 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), cyclopropylamine (3,35 g of 58.7 mmol) in ClCH2CH2Cl (80 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture in portions over 1.5 h added NaBH(OAc)3(4×2.1 g, is 39.2 mmol). The resulting mixture was stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth and washed with CH2Cl2(500 ml). The filtrate was washed with saturated aqueous NaHCO3(1×250 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a pale yellow oil. The crude product is purified on SiO2(330 g; 0-5% CH3OH/CH2Cl2getting white solid (3,95 g, yield 68%). MS (ESI): mass calculated for C17H16N2OS, 296,1; found m/z 297,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,63 (d, 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 (c, 2H), 2,19-2,12 (m, 1H), 1,86 (users, 1H), 0,48-0,35 (m, 4H).

B.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) is CH 3CN (40 ml) at room temperature add N,N-diisopropylethylamine (3,48 ml, 20 mmol) followed by addition of tert-butyl methyl ether (2-bromacil)carbamino acid (3,36 g, 15 mmol). The resulting mixture was heated at 60ºC overnight. The mixture is cooled and dissolved in CH2Cl2(200 ml), washed with saturated aqueous NaHCO3(1×25 ml), and

H2About (2×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a pale yellow solid. The crude product is purified on SiO2(120 g; 0-50% ethyl acetate/hexane)to give white solid (3,44 g, yield 78%). MS (ESI): mass calculated for C24H29N3O3S, 439,2; found m/z 440,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), to 7.64 (d, J=8,1, 1H), 7,39-7,22 (m, 6H), 4.75 in (users, 1H), 3,74 (c, 2H), 3,25 (DD, J=5,8, 6,1, 2H), 2,65 (t, J=6,3, 2H), 1,82 is 1.75 (m, 1H), 1,43 (c, 9H), 0,54-of 0.48 (m, 2H), 0,43-0,37 (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 0ºC added dropwise triperoxonane acid in dioxane (4 ml). The resulting reaction mixture was stirred at room temperature for 2 h and concentrated under reduced pressure, obtaining the crude product as a pale relegable. The oil was dissolved in CH2Cl2(100 ml), washed with saturated aqueous NaHCO3(1×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the product as a clear oil. MS (ESI): mass calculated for C19H21N3OS, 339,1; found m/z 340,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), to 7.61 (d, J=8,1, 1H), 7,37-to 7.18 (m, 6H), 3.75 to (c, 2H), was 2.76 (t, J=6,3, 2H), 2,60 (t, J=6,3, 2H), 1,98 (c, 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-he

To a solution of N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine (1.5 g, 4.4 mmol) in CH3CN (18 ml) at room temperature add N,N-diisopropylethylamine (1,15 ml, 6,63 mmol) followed by addition of ethyl ester of 4-(R)-bromo-3-hydroxybutiric acid (1,11 g, 5.3 mmol). The resulting mixture was heated at 60ºC overnight. The mixture is cooled and dissolved in CH2Cl2(100 ml), washed with saturated aqueous NaHCO3(1×10 ml), and

H2About (2×10 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as light brown oil. The crude product is purified HPLC with reversed phase (0-99%, 0,05% TFA in H2O/CH3CN)to give a clear oil (435 mg, yield of 18.3%). MS (ESI): mass calculated for C23H25N3O3S, 423,2; found m/z 424,3 [+H] +.

1H NMR (400 MHz, CD3OD): to 7.64 (d, J=8,1, 1H), 7,58-rate of 7.54 (m, 2H), 7,49 (d, 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 (d, J=17,2, 1H), 0,79 (d, J=6,6, 4H).

EXAMPLE 255

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

A.tert-Butyl ether ({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 ClCH2CH2Cl (172 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture in portions over 1.5 h added NaBH(OAc)3(4×1,82 g, to 34.4 mmol). The resulting mixture was stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth and washed with CH2Cl2(300 ml). The filtrate was washed with saturated aqueous NaHCO3(1×50 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a pale yellow oil. The crude product is purified on SiO2(330 g; 0-100% ethyl acetate/hexane), receiving light yellow foam (3.75 g, yield 48%). MS (ESI): mass calculated for C25H31N3O3S, 453,2; found m/z 454,5 [MH] +.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, 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 (c, 2H), 2,93 (d, J=11,6, 2H), 2,74 (c, 3H), 2,08 (t, J=11,6, 2H), 1,81 was 1.69 (m, 2H), 1,65-1,57 (m, 2H), 1,46 (c, 9H).

B.{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 0ºC is 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 produce the Desired product by filtration and washed with Et2O (150 ml)to give a white powder (to 3.38 g, yield 97%). MS (ESI): mass calculated for C20H23N3OS, 353,2; found m/z 354,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 8,92 (users, 1H), 7,72 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,39-7,33 (m, 3H), 7,30-7,21 (m, 3H), 3,49 (c, 2H), 2,98-of 2.86 (m, 3H), 2.63 in (c, 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 add TEA (to 0.70 ml, 5.0 mmol) followed by the addition of 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 us the seal water NaHCO 3(1×25 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a pale yellow solid. The crude product is purified on SiO2(40 g; 0-10% CH3HE/CH2Cl2)to give white solid (378 mg, yield 88%). MS (ESI): mass calculated for C21H25N3O3S2, 431,1; found m/z 432,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, 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 (c, 2H), 2,96 (d, J=11,6, 2H), 2,82 (c, 3H), 2,80 (c, 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 stage 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 a mixture of 30% THF/CH2Cl2(35 ml) was stirred at room temperature for 30 minutes To the mixture add Na(AcO)3BH (787 mg, 3.7 mmol). After 20 h the reaction mixture was added to a mixture of 10% iPrOH/H2About (50 ml), the organic layer separated and dried (MgSO4). The solvent is removed under reduced pressure, obtaining a transparent yellow sticky oil. The resulting material is diluted with ethanol (10 ml), heated to 80ºC and filtered hot. To the filtrate add Et2About (10 ml) and the flask is cooling the t on ice. The formed solid is filtered off, getting a white solid (48 mg, yield 5%). MS (ESI): mass calculated for C20H20N6OS, 392,1; found m/z 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), 3,59 (c, 2H), 3,09-3,00 (m, 1H), only 2.91 (d, 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]piperidine-1-yl}-2-hydroxyethane

A.tert-Butyl ether 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid

A mixture of 4-(benzothiazol-2-yloxy)benzaldehyde (2.5 g, 9.8 mmol), 2-he-tert-butyl ether piperazine-1-carboxylic acid (3.7 g, a 19.6 mmol) and molecular sieves (2.5 g, chipped, 4Å) in ClCH2CH2Cl (25 ml) was stirred at room temperature for 40 minutes To the resulting reaction mixture in portions over 1.5 h added NaBH(OAc)3(4×504 mg and 19.6 mmol). The reaction 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 NaHCO3(1×50 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a yellow semi-solid substances. The crude product is purified on SiO2(120 g; 0-100% acetone/CH2Cl2), receiving n is completely white solid (1,72 g, yield 42%). MS (ESI): mass calculated for C23H27N3O3S, 425,5; found m/z 426,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (c, 2H), 3.45 points (ushort, J=4,9, 4H), 2,41 (ushort, J=4,5, 4H), 1,46 (c, 9H).

B.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 0ºC added dropwise 4n. HCl in dioxane (5 ml, 20 mmol). The resulting mixture was stirred at room temperature for 2 h and concentrated under reduced pressure, obtaining the crude product as a white solid. The crude product is triturated in Et2About (50 ml) and was isolated by filtration, obtaining the desired product as a white powder (1,37 g, yield 87%). MS (ESI): mass calculated for C18H19N3OS, 325,4; found m/z 326,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,81 (d, J=8,0, 1H), to 7.77-7,72 (m, 2H), 7.62mm (d, J=8,2, 1H), EUR 7.57-7,53 (m, 2H), 7,45-7,40 (m, 1H), 7,35-7,31 (m, 1H), 4,45 (c, 2H), 3,62 (users, 8H).

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

To a mixture of glycolic acid (47 mg, of 0.62 mmol) and HOBT (1.25 ml, of 0.62 mmol, 0,5M in DMF) in CH2Cl2(25 ml) is added 2-(4-piperazine-1-ylmethylene)benzothiazole (150 mg, 0.42 mmol) followed by addition of EDCI (150 mg, 0.79, which mmol). The resulting mixture plumage is eshivot at room temperature for 24 h, diluted with CH2Cl2(50 ml) and washed with saturated aqueous NaHCO3(1×20 ml). The organic layer is dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a pale yellow oil. The crude product is purified on SiO2(40 g; 0-3% 2M NH3in CH3OH/CH2Cl2)to give a white foam (93 mg, yield 59%). MS (ESI): mass calculated for C20H21N3O3S, 383,5; found m/z 384,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), 7,68 (d, J=8,0, 1H), 7,45-7,25 (m, 6H), 4,16 (d, J=4,1, 2H), 3,71-3,68 (m, 2H), 3,64-3,61 (m, 1H), 3,55 (c, 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 ether ({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, chipped, 4Å) in ClCH2CH2Cl (15 ml) was stirred at room temperature for 40 minutes To the mixture in portions over 1.5 h added NaBH(OAc)3(4×412 mg, 7.8 mmol). The mixture is stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth and washed with CH2Cl2(100 ml). The filtrate is washed on Ishenim aqueous NaHCO 3(1×50 ml), dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a yellow semi-solid substances. The crude product is purified SiO2(40 g; 0-100% acetone/CH2Cl2)to give a white foam (890 mg, yield 50%). MS (ESI): mass calculated for C25H31N3O3S, 453,6; found m/z 454,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), to 7.67 (d, J=8,0, 1H), 7,41-of 7.36 (m, 3H), 7,32-7,24 (m, 3H), 4,59 (users, 1H), 3,50 (c, 2H), 3,06-3,00 (m, 2H), 2,94-is 2.88 (m, 2H), 1,97 (t, J=11,4, 2H), 1,68 (d, J=11,4, 2H), 1,44 (c, 9H), to 1.22 and 1.33 (m, 2H).

B.C-{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 0ºC added dropwise 4n. HCl in dioxane (2.4 ml, 9.5 mmol). The resulting mixture was stirred at room temperature for 24 h and concentrated under reduced pressure, obtaining the crude product as a white solid. The crude product is triturated in Et2About (50 ml) and was isolated by filtration, obtaining the desired product as a white powder (813 mg, yield 100%). MS (ESI): mass calculated for C20H23N3OS, 353,5; found m/z 354,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,80 (d, J=8,0, 1H), 7,69 (d, J=8,6, 2H), 7,60 (d, J=8,0, 1H), 7,51 (d, J=8,6, 1H), 7,42-7,38 (m, 1H), 7,33-7,28 (m, 1H), 4,37 (c, 2H), 3,78 (shirt, J=12,7, 1H), 2H), 3,13 totaling 3.04 (m, 2H), 2,89 (d, 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 resulting mixture was cooled to 0ºC and syringe add CH3SO2Cl (41 μl, 0.52 mmol). The mixture is stirred at room temperature for 24 h, diluted with CH2Cl2(10 ml) and washed with saturated aqueous NaHCO3(1×5 ml). The organic layer is dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as a white solid. The crude product is purified on SiO2(10 g; 0-3% 2M NH3in a mixture of CH3OH/CH2Cl2)to give white solid (112 mg, yield 67%). MS (ESI): mass calculated for C21H25N3O3S, 431,6; found m/z 432,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (ushort, J=6,6, 1H), 3,51 (c, 2H), 3.04 from (d, J=6,6, 2H), 2,96 (c, 3H), 2.91 in-2,84 (m, 2H), 1,98 (t, J=11,7, 2H), 1,74 (userd, 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 who, 54 mmol) and ethanolamine (13,2 ml, 218 mmol) in CH3OH (20 ml) add cyanoborohydride sodium (10.2 g, 163 mmol) and triftormetilfullerenov acid (5 ml) and the reaction mixture was stirred at 23º C for 3 days. The mixture is cooled to 0ºC and slowly add n. HCl as long as you do not stop the gas, and the resulting mixture is stirred for another 3 hours the Mixture is filtered and the filtrate concentrated under reduced pressure. Crude oil is again dissolved in N2About (50 ml), the solution is alkalinized by adding 10h. NaOH. The mixture is extracted with CH2Cl2(8×70 ml). United CH2Cl2the extracts are dried and concentrated under reduced pressure, obtaining the crude product (12.0 g, 95%). A solution of 2-(1-benzylpiperidine-4-ylamino)ethanol (3.6 g, of 15.3 mmol) in ClCH2CH2Cl (5 ml) is treated with carbonyl diimidazol (CDI) (2.6 g, 16 mmol) and the mixture is stirred at 23º C for 30 minutes the Mixture was diluted with CH2Cl2(100 ml), washed with H2About (1×50 ml) and saturated aqueous NaHCO3(1×50 ml), dried and concentrated under reduced pressure, obtaining 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 ClCH2CH2Cl (40 ml) add b-chlorantraniliprole (1.5 g, 10.6 mmol) and the mixture is heated to 100ºC for 90 minutes the Mixture is cooled to 23ºC and concentrate at bonigen the m pressure. The crude residue was dissolved in CH3OH and heated at boiling temperature under reflux for 1 h the Mixture is cooled to 0ºC and concentrated under reduced pressure, obtaining mentioned in the title compound (1.89 g, 99%). MS (ESI): exact mass calculated for C8H14N2O2, USD 170.1; found m/z 171,2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,97 (users, 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 a, 6,6, 1H), 3,30 (userd, 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).

B.[4-(Benzothiazol-2-yloxy)phenyl]methanol

To a mixture of 4-hydroxybenzoato alcohol (12 g, 97 mmol) in CH3CN (200 ml)containing K2CO3(22 g, 159 mmol), is added 2-chlorobenzothiazole (22 g, 130 mmol) and the mixture is heated at boiling temperature under reflux for 72 hours the Mixture is cooled to room temperature, filtered and concentrated under reduced pressure, obtaining the crude product as a Golden oil. The resulting oil purified on SiO2(300 g; 5% acetone/CH2Cl2), getting a clear colorless oil. (15 g, yield 60%). MS (ESI): exact mass calculated for C14H11NO2S, 257,1; found m/z 258,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=7,4, 1H), 7,69 (d, J=8,0, 1H), 7,50-7,31 (m, 5H), 7,32 (t, J=7,5, 1H), 5,32 (t, J=5,7, 1H), 4,55 (d, J=5,7, 2H).

C.2-(4-Chloromethylene)benzothiazole

To the mixture is [4-(benzothiazol-2-yloxy)phenyl]methanol (11 g, 43 mmol) in CH2Cl2(100 ml)containing triethylamine (9 ml, 65 mmol)at 5ºC added dropwise within 15 minutes, thionyl chloride (4 ml g, 55 mmol). Bath ice is removed, the mixture warmed to room temperature and stirred for 24 hours the Mixture is washed once with saturated K2CO3(100 ml), dried (MgSO4) and concentrated under reduced pressure, obtaining the black oil. The crude oil is purified on SiO2(300 g; 100% CH2Cl2), getting a clear orange oil. (10 g, yield 84%). MS (ESI): exact mass calculated for C14H10ClNOS, 275,0; found m/z 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 (d, J=8,6, 2H), 7,37 (t, J=7,4, 1H), 7,33 (t, J=7,5, 1H), 4,84 (c, 2H).

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

To a mixture of 2-(4-chloromethylene)benzothiazole (670 mg, 2.4 mmol) in CH3CN (15 ml)containing K2CO3(544 mg, 3.9 mmol), type cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it (355 mg, 1.7 mmol) and the mixture is heated to 60ºC for 24 hours the Mixture is cooled to room temperature, filtered and concentrated under reduced pressure, obtaining the crude product as a Golden oil. The crude oil is purified on SiO2(12 g; acetone)to give white solid (591 mg, yield 84%). MS (ESI): mass calculated for C22H23N O3S, 409,2; found m/z 410,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=8,7, 1H), of 7.70 (d, J=7,5, 1H), of 7.48-7,37 (m, 5H), 7,33 (d, J=8,0, 1H), 4,25 (t, J=7,7, 2H), 3,60-of 3.42 (m, 5H), 2,85 (d, 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 ml, 218 mmol) in CH3OH (20 ml) add cyanoborohydride sodium (10.2 g, 163 mmol) and triftormetilfullerenov acid (5 ml) and the reaction mixture was stirred at 23º C for 3 days. The mixture is cooled to 0ºC and slowly add n. HCl as long as you do not stop the gas, and the resulting mixture is stirred for another 3 hours the Mixture is filtered and the filtrate concentrated. Crude oil is again dissolved in N2About (50 ml) and the solution is alkalinized by adding 10h. NaOH. The mixture is extracted with CH2Cl2(8×70 ml). United CH2Cl2the extracts are dried and concentrated under reduced pressure, obtaining 12.0 g (yield 95%) of the crude product. A solution of 2-(1-benzylpiperidine-4-ylamino)ethanol (2,13 g, 9.1 mmol) in ethanol (11 ml) and H2O (5 ml)at 0 ° C, treated simultaneously chloroacetylation (1.8 ml, 22.7 mmol) and 35% aq. NaOH solution and the mixture is stirred at a temperature below 20ºC for 3 hours, Reactio the ing mixture is diluted with H 2O (20 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers washed with saturated salt solution, dried and concentrated, getting 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 ClCH2CH2Cl (20 ml) add b-chlorantraniliprole (660 mg, 4.6 mmol) and the reaction mixture is heated to 100ºC for 16 hours the Mixture is cooled to 23ºC and concentrate under reduced pressure. The crude substance is purified on SiO2(12 g, 0-10% 2M ammonia in a mixture of CH3OH/CH2Cl2)to give 282 mg (yield 53%) of 4-piperidine-4-Immortalis-3-one. MS (ESI): exact mass calculated for C8H14N2O2, 184,1; found m/z 185,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 3,72 (c, 2H), equal to 2.94 (t, J=6,6, 2H), by 2.55 (t, J=3,6, 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).

B.4-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl)morpholine-3-one

Specified in the header connection receive in accordance with example 259, step D. MS (ESI): exact mass calculated for C24H27N3O3S, 423,16; found m/z 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 (c, 2H), 3,90 (t, J=4,9, 2H), 3,56 (c, 2H), 3,34 (t, J=5,1, 2H), 3,01 (userd, 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), 1,7-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.Salt of acetic acid (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 ml of 13.1 mmol) in CH3CN (12 ml) is treated with (R)-4-bromo-3-hydroxybutyrate (1.4 g, 6.8 mmol) and the mixture is heated at 65ºC for 48 hours the Mixture is cooled and diluted with ethyl acetate (70 ml) and washed with H2O (20 ml). The organic layer is dried, concentrated under reduced pressure and the crude residue purified on SiO2(12 g, 0-5% 2M ammonia in a mixture of CH3OH/CH2Cl2). The product is dissolved in ethanol (20 ml) and heated to 80ºC for 48 hours the Mixture is concentrated under reduced pressure and the crude residue purified on SiO2(12 g, 0-5% 2M ammonia in a mixture of CH3OH/CH2Cl2)to give 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) is treated with Pd(OH)2(60 mg) and the mixture loaded gas-hydrogen in a Parr apparatus to a pressure of 50 lb/in2and subjected to shaking for 5 days. The mixture is filtered through a layer of diatomaceous earth and concentrated, gaining 280 mg (yield 91%) specified in the connection header, cat is PoE use in the next stage without purification. MS (ESI): exact mass calculated for C9H16N2O2, 184,1; found m/z 185,2 [M+H]+.

B.(R) 1-(1-(2-[4-(Benzothiazol-2-yloxy)phenoxy]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he

Specified in the header connection receive in accordance with example 24, using a salt of acetic acid 4-hydroxy-1-piperidine-4-iparralde-2-it. MS (ESI): exact mass calculated for C24H27N3O4S, 453,2; found m/z 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 a, 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), 4,18-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 ml, 56 mmol) in CH3CN is treated with finely powdered Cs2CO3(27 g, 84 mmol) and the resulting mixture was stirred at 40ºC for 17 h at 60ºC for 2 h, the Reaction mixture was filtered through a layer of diatomaceous earth and the filtrate concentrated under reduced pressure. The crude solid is purified by dissolving in ethyl acetate (350 ml) and what romavarium 10% NaOH (3×30 ml), 0,5M citric acid (1×30 ml), saturated aqueous NaHCO3(1×30 ml), saturated salt solution (1×30 ml), then dried over Na2SO4, filtered and concentrated under reduced pressure, obtaining 16 g (yield 95%) of methyl ester [4-(benzothiazol-2-yloxy)phenyl]acetic acid as a white solid. A solution of methyl ester [4-(benzothiazol-2-yloxy)phenyl]acetic acid (5.4 g, 18 mmol) in 80 ml of toluene at-90ºC treated, dropwise adding 1,0M solution diisobutylaluminium in hexano (27 ml, 27 mmol). The reaction mixture is slowly heated to-68ºC for 30 min and then quenched by adding methanol (2.0 ml). The reaction mixture is heated -20 ░ C, diluted with diethyl ether (100 ml) and 2,0M HCl (60 ml) and vigorously stirred for 30 minutes the Organic layer was separated, washed with saturated aqueous NaHCO3, dried over

Na2SO4, filtered and concentrated, obtaining specified in the header connection (4,84 g, yield 99%).

B.2-(4-{2-[4-(1H-Tetrazol-5-yl)piperidine-1-ileti}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), treated with triacetoxyborohydride sodium (599 mg, 2.7 mmol) and the mixture is stirred at room temperature for 24 h the Mixture was washed with asystem aqueous NaHCO 3(15 ml), dried (MgSO4) and concentrated under reduced pressure, obtaining a white solid. The solid is washed with diethyl ether, receiving the product as a white solid (214 mg, yield 23%). MS (ESI): mass calculated for C21H22N6OS, 406,2; found m/z 407,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to 7.93 (d, J=7,9, 1H), 7,69 (d, J=7,7, 1H), of 7.48-7,30 (m, 6H), 3,10 (d, 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 (d, 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 header connection receive in accordance with the method of example 24, using piperidine-2-ylmethanol. MS (ESI): mass calculated for C21H24N2O2S, 384,2; found m/z 385,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to $ 7.91 (d, J=7,9, 1H), 7,68 (d, J=8,0, 1H), 7,42 (t, J=7,3, 1H), 7,37 (d, J=9,0, 2H), 7,31 (t, J=8,1, 1H), 7,05 (d, 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 (d, 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 header connection receive in accordance with the method of example 24, using ethyl ether (1H-tetrazol-5-yl)acetic KIS is the notes. MS (ESI): mass calculated for C20H19N5O4S, 425,1; found m/z 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 (d, J=9,1, 2H), 4,88 (t, J=5,0, 2H), 4,43 (t, J=5,0, 2H), 4,35 (c, 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 header connection receive in accordance with the method of example 24, using piperidine-3-ylmethanol. MS (ESI): mass calculated for C21H24N2O3S, 384,2; found m/z 385,1 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (d, J=8,1, 1H), 7,68 (d, 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 (d, 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]phenoxybenzoate

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-1-carboxylic acid (404 mg, 1.6 mmol) in CH3CN (10 ml) add Cs2CO3(537 mg, 1.7 m is ol). The mixture is heated at 60ºC for 20 h and then filtered. The filtrate is concentrated under reduced pressure to a clear Golden oil, which was purified on SiO2(40 g; 0-15% acetone/CH2Cl2)to give white solid (483 mg, yield 65%). TLC (SiO215% acetone/CH2Cl2: Rf=0,84. MS (ESI): mass calculated for C26H30N6O4S, 522,2; found m/z 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 (d, J=6,9, 2H), of 5.05 (t, J=4,7, 2H), 4,57 (t, J=4,8, 2H), 3,92 (d, J=12,4, 2H), 3,20-of 3.12 (m, 1H), 2,96 (users, 2H), 1,97 (DD, J=13.3-inch, 3, 2H), 1,65-of 1.52 (m, 2H), 1,40 (c, 9H).

B.Hydrochloride of 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) is added concentrated HCl (75 μl, 0,009 mmol). The mixture is stirred at room temperature for 20 h and concentrated under reduced pressure, obtaining a clear, colorless oil. The oil is dried in high vacuum for 2 h and receive a white solid (337 mg, yield 99%). MS (ESI): mass calculated for C21H22N6O2S, 422,2; found m/z 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 (d, J=9,4, 2H), 7,32 (t, J=7,4, 1H), 5,08 (t, 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 (d, 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 header connection receive in accordance with the method of example 24 using 4-Spiro[3-phtalic]piperidine. MS (ESI): mass calculated for C27H24N2O4S, 472,2; found m/z 473,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=7,9, 1H), 7,83 (d, 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 (d, J=9,1, 2H), 4,19 (t, J=5,7, 2H), 3,05 (d, 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 (d, J=12,5, 2H).

EXAMPLE 268

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

Specified in the header connection receive in accordance with the method of example 35, using ethyl ether piperidine-4-carboxylic acid stage and 2-chlorobenzothiazole on stage C. MS (ESI): mass calculated for C24H28N2O3S, 424,2; found m/z 425,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=7,9, 1H), 7,68 (d, J=8,0, 1H), 7,43 (t, J=8,1, 1H), 7,38-7,28 (m, 5H), of 4.05 (q, J=7,1, 2H), 2,78 (d, J=11,3, 2H), 2.63 in (t, J=7,5, 2H, in), 2.25 (t, J=7,0, 3H), of 1.93 (t, J=13,2, 2H), 1,84 by 1.68 (m, 4H), and 1.54 (kV, J=14,9, 2H), of 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 a stirred solution of di-tert-BUTYLCARBAMATE (34,2 g, 157 mmol) in THF (200 ml) add tyramine (21,3 g, 155 mmol) in THF (100 ml) for 1 h, the Mixture is stirred for 2.5 h and concentrated under reduced pressure to a clear Golden oil, which was purified on SiO2(300 g; 0-25% acetone/CH2Cl2). The desired fractions are combined and concentrated under reduced pressure, obtaining the product as a pink oil (37 g, yield 100%). TLC (SiO2with 5% acetone/CH2Cl2): Rf=0,31. MS (ESI): mass calculated for C13H19NO3, 237,1; found m/z of 260.2 [M+Na]+.

1H NMR (400 MHz, DMSO-d6): 9,16 (c, 1H), of 6.96 (d, J=8,4, 2H), 6,82 (c, 1H), 6,66 (d, J=8,4, 2H), 3,05 (kV, J=8,3, 2H), has 2.56 (t, J=8,1, 2H), 1,37 (c, 9H).

B.tert-Butyl ether {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}carbamino acid

Specified in the header connection receive, following the method of example 30, step B, using tert-butyl ether [2-(4-hydroxyphenyl)ethyl]carbamino acid, to obtain white solid (9 g, yield 56%). TLC (SiO2, CH2Cl2): Rf=0,19. MS (ESI): mass calculated for C20H22N2O3S, 370,1; found m/z 371,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=7,9, 1H), 7,68 (d, J=8,0, 1H), of 7.48-7,30 (m, 6H), 7,34 (t, J=7,8, 1H), 3,09 (d, J=7,1, 2H), 2,75 (t, J=7,, 2H), 1,38 (c, 9H).

C. Ghydrochloride 2-[4-(benzothiazol-2-yloxy)phenyl]ethylamine

Specified in the header connection receive in accordance with the method of example 266, step In, getting a white solid (6.4 g, yield 100%). MS (ESI): mass calculated for C15H14N2OS, 270,1; found m/z 271,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,05 (users, 2H), 7,94 (d, J=7,8, 1H), 7,68 (d, 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 points (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) is added hydroquinone (10.0 g, 91,2 mmol) for 30 minutes. The mixture is then heated to 80 ° C for 2 h and cooled to room temperature. To a stirred mixture of 2-chlorobenzothiazole (11.3 ml of 91.3 mmol) for 30 minutes and the mixture is stirred at room temperature for 24 hours To the mixture of methyl 2-bromoacetate (8.6 ml, the 90.8 mmol) for 30 minutes and the mixture is stirred for 24 hours To the mixture of N2O (1 l) and the product extracted with Et2O (2×500 ml), dried (MgSO4) and concentrated under reduced pressure, obtaining a beige solid. The solid is stirred in CH2Cl2(200 ml) and filtered, and p is the best product in the form of a white solid (24.2 g, yield 84%). MS (ESI): mass calculated for C16H13NO4S, 315,1; found m/z 316,2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 7.92 (d, J=8,0, 1H), 7,66 (d, J=8,1, 1H), 7,47-7,40 (m, 3H), 7,32 (t, J=7,5, 1H), 7,07 (d, J=8,6, 2H), 4,87 (c, 2H), of 3.73 (c, 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-78º added DIBAL-H (5 ml, 5 mmol), keeping the temperature below-75º. The mixture was stirred at-72º for 4 h and quenched with H2About (10 ml), extracted with CH2Cl2(2×10 ml), dried (MgSO4) and concentrated under reduced pressure, getting a clear Golden oil (708 mg, yield 78%). MS (ESI): mass calculated for C15H11NO3S, 285,1; found m/z 286,3 [M+H]+.

C.2-(4-{2-[4-(1H-Tetrazol-5-yl)piperidine-1-yl]ethoxy}phenoxy)benzothiazole

Specified in the header connection receive according to the method of example 262, step B, using 4-(1H-tetrazol-5-yl)piperidine. MS (ESI): mass calculated for

With21H22N6O2S, 422,2; found m/z 422,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to 7.93 (d, J=7,8, 1H), 7,68 (d, J=7,9, 1H), 7,49-7,40 (m, 3H), 7,33 (t, J=7,3, 1H), 7,14 (d, 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), of 2.25 (d, J=12,0, 2H), 2,18-2,02 (m, 2H).

EXAMPLE 271

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

A.u> 4-piperidine-1-ylmethylene

A mixture of 4-hydroxybenzaldehyde (10 g, 82 mmol), piperidine (16 ml, 164 mmol) and molecular sieves (10 g, chipped, 4Å) in ClCH2CH2Cl (150 ml) was stirred at room temperature for 40 minutes To the resulting mixture is added in portions over 1.5 h NaBH(OAc)3(7×5 g, 164 mmol). The mixture is stirred at room temperature for 24 h the mixture was diluted with CH2Cl2(300 ml), filtered through a layer of diatomaceous earth and washed with additional amount of CH2Cl2(100 ml). The filtrate was washed with saturated aqueous NaHCO3(3×150 ml), extracted with a mixture of 25% isopropanol/CHCl3, dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product as an orange semi-solid substances. The crude product is purified on SiO2(120 g; 0-100% acetone/CH2Cl2), receiving a yellow solid (is 3.08 g, yield 48%). MS (ESI): mass calculated for C12H17NO, 191,1; found m/z 192,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.18 (d, J=8,4, 2H), 6.75 in (d, J=8,4, 2H), 3,83 (c, 2H), 2,81 (users, 4H), 1.77 in (quintet, J=5,7, 4H), and 1.54 (users, 2H).

B.2-(4-piperidine-1-ylmethylene)benzoxazol

Specified in the header connection receive in accordance with the method of example 13, step B, using 4-piperidine-1-ylmethylene. MS (ESI): mass calculated for C19H20N 2O2, 308,2; found m/z 309,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): to 7.64 (d, J=3.1 Hz, 1H), 7,52 (d, J=8,9 Hz, 1H), and 7.3 (kV, J=8,3 Hz, 4H), 7,34-7,26 (m, 2H), 3.45 points (c, 2H), 2,33 (users, 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 header connection receive in accordance with the method of example 259, step D using cyclohexylethylamine. MS (ESI): mass calculated for C22H26N2OS, 366,2; found m/z 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 (d, J=8,6, 2H), 7,33 (t, J=8,3, 1H), 3,63 (c, 2H), 2,58-to 2.41 (m, 3H), of 1.76 (t, J=11,9, 4H), 1,58 (d, J=12,1, 1H), 1.32 to 1,01 (m, 5H), of 0.95 (t, J=7,1, 3H).

EXAMPLE 273

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

Specified in the header connection receive in accordance with the method of example 259, step D using (2-cyclopropylethyl)ethylamine. MS (ESI): mass calculated for C21H24N2O2S, 352,2; found m/z 353,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=8,0, 1H), of 7.70 (d, J=8,1, 1H), 7,45 (t, J=8,5, 3H), 7,39 (d, J=8,6, 2H), 7,33 (t, J=8,0, 1H), 3,66 (c, 2H), 2,53 is 2.44 (m, 3H), 2,32 (d, J=6,5, 2H), 1,54-of 1.42 (m, 2H), 1.32 to a 1.01 (m, 5H)to 0.85 (d, J=7,3, 4H), 0,45 (d, 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 header connection receive in accordance with the method of example 259, step D using amide piperidine-4-carboxylic acid. MS (ESI): mass calculated for C20H21N3O2S, 367,1; found m/z 368,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=7,4, 1H), of 7.70 (d, J=7,9, 1H), of 7.48-7,38 (m, 5H), 7,33 (d, J=7,1, 1H), 7,22 (c, 1H), 6.73 x (c, 1H), 3,49 (c, 2H), and 2.83 (d, 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-(Benzothiazol-2-yloxy)benzyl]-[1,4']bipyridinyl-2-he

Specified in the header connection receive in accordance with the method of example 259, step D using [1,4']bipyridinyl-2-it. MS (ESI): mass calculated for C24H27N3O2S, UAH 421,2; found m/z 422,5 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=8,8, 1H), of 7.70 (d, J=8,6, 1H), of 7.48-7,38 (m, 5H), 7,33 (d, J=9,0, 1H), 4,37-of 4.25 (m, 1H), 3,52 (c, 2H), and 3.16 (t, J=5,2, 2H), 2,89 (d, J=11,2, 2H), 0 2,22 (t, J=6,6, 2H), 2,03 (t, J=11,1, 2H), 1,78 is 1.58 (m, 6H), of 1.45 (d, J=10,8, 2H).

EXAMPLE 276

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

Specified in the header connection receive in accordance with the method of example 259, step D using piperazine-1-espiridion-3-ylmethanol. MS (ESI): mass calculated for C24H22N24O2S, 430,2; found m/z 431,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,65 (d, J=4,8, 1H), ,61 (d, J=1,9, 1H), 7,94 (d, J=7,9, 1H), to 7.84 (d, J=7,8, 1H), 7,69 (d, J=8,0, 1H), 7,60-7,40 (m, 6H), 7,33 (d, J=8,3, 1H), 3,64 (users, 2H), to 3.58 (c, 2H), 3,37 (users, 2H), 2,41 (users, 4H).

EXAMPLE 277

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

Specified in the header connection receive in accordance with the method of example 259, step D, using tert-butyl ether piperidine-4-iletilerinindeki acid. MS (ESI): mass calculated for C25H31N3O3S, 453,2; found m/z 454,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=7,3, 1H), of 7.70 (d, J=7,9, 1H), of 7.48-7,37 (m, 5H), 7,33 (d, J=8,2, 1H), 6,85 (t, J=5,9, 1H), 3,48 (c, 2H), 2,86 was 2.76 (m, 4H), 1,90 (t, J=11,1, 2H), and 1.56 (d, J=11.8 in, 2H), 1,37 (c, 10H), a 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 header connection receive in accordance with the method of example 258, step C, using methylchloroform. MS (ESI): mass calculated for C22H25N3O3S, 411,2; found m/z 412,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=7,9, 1H), of 7.70 (d, J=8,0, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (d, J=8,0, 1H), 7,17 (t, J=5,6, 1H), 3,51 (c, 3H), 3,48 (c, 2H), 2,87 (t, J=6,2, 2H), 2,80 (d, J=11,1, 2H), 1,90 (t, J=10,5, 2H), 1,60 (t, J=12,8, 2H), 1,38 (users, 1H), 1,20 was 1.06 (m, 2H).

EXAMPLE 279

tert-Butyl ether N-{C-[[4-(benzo is a thiazol-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 B, 657 mg, 1.5 mmol) in CH2Cl2(15 ml)containing triethylamine (1 ml, 7.2 mmol), add N-(sulphonylchloride)tert-butyl ether carbamino acid (440 mg, 2.1 mmol). The mixture is stirred for 48 hours, bring in CH2Cl2(50 ml), washed once with H2O (75 ml), dried (MgSO4) and concentrated under reduced pressure, obtaining a clear, colorless oil. The oil is purified on SiO2(12 g, 0-50% acetone/CH2Cl2), the desired fractions are combined and concentrated under reduced pressure, obtaining a white solid (112 mg, yield 14%). TLC

(SiO2, 50% acetone/CH2Cl2): Rf=0,40. MS (ESI): mass calculated for C25H32N4O5S2, 532,2; found m/z 533,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): a 10.74 (users, 1H), of 7.90 (d, J=7,9, 1H), 7,66 (d, J=8,0, 1H), 7,54 (users, 1H), 7,44-7,34 (m, 5H), 7,30 (d, J=8,3, 1H), 3,48 (c, 2H), 2,84-2,70 (m, 4H), 1,90 (t, J=10,4, 2H), 1,64 (d, J=11,4, 2H), 1,38 (c, 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 is obtained from the compound of example 279, following the method of example 266, step C. MS (ESI): mass calculated for C20H24N4O3S2, 432,1; found m/z433,4 [M+H] +.

1H NMR (400 MHz, DMSO-d6): 10,08 (users, 1H), 7,80 (d, J=8,2, 1H), 7,76-to 7.68 (m, 3H), 7,58 (d, J=8,6, 2H), 7,45 (t, J=8,4, 2H), was 7.36 (t, J=8,8, 2H), 6,70-6,50 (users, 2H), 4,33 (d, J=5,4, 2H), 3.00 and-2,86 (users, 1H), 2,77 (t, J=6,2, 2H), at 1.91 (d, J=13,4, 2H), 1,71 (users, 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 header connection receive in accordance with the method of example 258, step C, using acetylchloride. MS (ESI): mass calculated for

With22H25N3O2S, 395,2; found m/z 396,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, 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 (d, J=8,2, 1H), 3,48 (c, 2H), 2,93 (t, J=6,2, 2H), 2,81 (d, J=11,4, 2H), 1.91 a (t, J=11,3, 2H), 1,80 (c, 3H), to 1.61 (d, J=11,0, 2H), 1,38 (users, 1H), 1,20 was 1.06 (m, 2H).

EXAMPLE 282

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

Specified in the header connection receive in accordance with the method of example 259, step D using ethyl ether piperidine-4-luxusni acid, and example 250, step D. MS (ESI): mass calculated for C21H22N2O3S, 382,1; found m/z 383,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 10,1 (users, 1H), of 7.97 (d, J=7,9, 1H), of 7.70 (d, J=7,6, 3H), 7,58 (users, 2H), 7,45 (t, J=7,2, 1H), was 7.36 (t, J=7,3, 1H), or 4.31 (users, 1H), 2,98 (users, 3H), 2,20 (d, J=5,6, 3H), 1,87 (users, 4H)and 1.51 (users, 2H).

USE the 283

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

Specified in the header connection receive in accordance with the method of example 258, step D, using [(piperidine-4-ylmethyl)carbarnoyl]methyl ester acetic acid, and example 253, step D. MS (ESI): mass calculated for

With24H27N3O4S, 453,2; found m/z 454,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,01 (t, J=5,8, 1H), 7,94 (d, J=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 (c, 2H), 3,48 (c, 2H), 2,98 (t, J=6,3, 2H), 2,81 (d, J=11,4, 2H), 2,08 (c, 3H), 1.91 a (t, J=11,2, 2H), 1,60 (d, J=11,2, 2H), 1,42 (users, 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 is obtained from the compound of example 258, step B following the example 257, step C, using 2-tert-butoxycarbonylmethylene acid. MS (ESI): mass calculated for C30H38N4O4S, 550,3; found m/z 551,5 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, 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 (c, 2H), 2.95 points (t, J=6,1, 2H), 2,78 (t, J=9,6, 2H), 2,45 to 2.35 (m, 2H), 2.13 and (c, 1H), 2,05-of 1.95 (m, 2H), 1.93 and-to 1.70 (m, 4H), to 1.59 (d, J=10,9, 2H), 1,38 (c, 9H), 1,20-of 1.05 (m, 2H).

EXAMPLE 285

Digital the reed {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acid

Specified in the header connection receive in accordance with the method of example 266, step C. MS (ESI): mass calculated for C25H30N4O2S, 450,2; found m/z 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 (d, J=8,6, 3H), 7,71 (d, J=7,8, 1H), 7,45 (t, J=8,5, 1H), was 7.36 (t, J=7,1, 1H), 4,32 (c, 2H), 3,20 was 3.05 (m, 2H), 3.00 and-to 2.85 (m, 2H), 2,472 (d, 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), 1,68-1,50 (c, 2H).

EXAMPLE 286

2-(4-Pyrrolidin-1 ylmethylene)benzothiazole

Specified in the header connection receive in accordance with the method of example 259, step D using pyrrolidine. MS (ESI): mass calculated for C18H18N2OS, 310,1; found m/z 311,34 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=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 (c, 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 header connection receive in accordance with the method of example 259, step D using 2-ethylaminoethanol. MS (ESI): mass calculated for C18H20N2O2S, 328,1; found m/z 329,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, 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 (c, 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 header connection receive in accordance with the method of example 259, step D using 2-piperidine-2-retinol. MS (ESI): mass calculated for C21H24N2O2S, 368,2; found m/z 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 (c, 1H), 3,92 (d, J=14,0, 1H), 3,50 (users, 2H), and 3.31 (d, J=6,4, 1H), 2,70-2,60 (m, 1H), 2,14-2,03 (m, 1H), 1,87-of 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

Specified in the header connection receive in accordance with the method of example 259, step D using 1-piperazine-1-ylatason. MS (ESI): mass calculated for C20H21N3O2S, 367,1; found m/z 368,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=8,0, 1H), of 7.70 (d, J=7,5, 1H), of 7.48-7,39 (m, 5H), 7,33 (t, J=7,7, 1H), 3,55 (c, 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 (c, 3H).

EXAMPLE 290

8-[4-(Benzothiazol-2-yloxy)benzyl]-2,8-diazaspiro[4.5]Decan-1-he

Specified in the header connection receive in accordance with the method of example 259, step D using 2,8-diazaspiro[4.5]Decan-1-it. MS (ESI): mass calculated for C22H23N3O2S, 393,2; found m/z 394,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94(d, J=7,4, 1H), of 7.70 (d, J=8,0, 1H), 7,54 (c, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t, J=8,2, 1H), 3,51 (c, 2H), 3.15 in (t, J=6,8, 2H), 2,75 (d, 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 (d, J=12,8, 2H).

EXAMPLE 291

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

Specified in the header connection receive in accordance with the method of example 259, step D using Spiro[isobenzofuran-1(3H), 4'-piperidine]-3-one. MS (ESI): mass calculated for C26H22N2O3S, 442,1; found m/z 443,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): of 7.95 (d, J=7,9, 1H), 7,83 (d, 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 (c, 2H), 2,90 (d, J=11,1, 2H), is 2.41 (t, J=11,0, 2H), 2,28 (t, J=13,3, 2H), of 1.66 (d, J=12,6, 2H).

EXAMPLE 292

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

Specified in the header connection receive in accordance with the method of example 259, step D using (R)-pyrrolidin-3-ol. MS (ESI): mass calculated for C18H18N2O2S, to 326.1; found m/z 327,2 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, 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 (d, 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

The decree of the TES in the header connection receive in accordance with the method of example 259, stage D, using 2-methylpiperidin. MS (ESI): mass calculated for

With20H22N2OS, 338,2; found m/z 339,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, 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 (d, J=13,9, 1H), 3,19 (d, 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 (d, J=6,2, 3H).

EXAMPLE 294

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

Specified in the header connection receive in accordance with the method of example 259, step D using diethylamine. MS (ESI): mass calculated for

With18H20N2OS, 312,1; found m/z 313,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, 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), 3,57 (c, 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 header connection receive in accordance with the method of example 259, step D using butylmethylamine. MS (ESI): mass calculated for C19H22N2OS, 326,2; found m/z 327,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=7,9, 1H), of 7.70 (d, J=7,5, 1H), of 7.48 and 7.36 (m, 5H), 7,33 (t, J=8,0, 1H), 3,49 (c, 2H), 2,34 (t, J~ 7,1, 2H), 2.13 and (c, 3H), 1,50-of 1.40 (m, 2H), 1,38-1,24 (m, 2H), from 0.88 (t, J=7,3, 3H).

EXAMPLE 296

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

The decree is Noah in the header connection receive in accordance with the method of example 259, stage D, using 2-piperidine-4-retinol. MS (ESI): mass calculated for C21H24N2O2S, 368,2; found m/z 369,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,74 (d, J=7,9, 1H), 7,49 (d, 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 (c, 2H), 3,23 (kV, J=6,2, 2H), 2,59 (d, J=11,1, 2H), 1,72 (t, J=10,3, 2H), 1,42 (d, 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 header connection receive in accordance with the method of example 259, step D using piperidine-4-ol. MS (ESI): mass calculated for C19H20N2O2S, 340,1; found m/z 341,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=7,9, 1H), 7,68 (d, J=8,0, 1H), 7,46 and 7.36 (m, 5H), 7,32 (t, J=8,1, 1H), 4,60 (d, J=4,9, 1H), to 3.58 is 3.40 (m, 3H), 2,80 (d, J=9,9, 1H), 2,65 (d, J=10,7, 1H),1,87 (t, J=9,2, 1H), 1,80 (d, J=8,6, 1H), 1,71 (t, J=9,8, 1H), 1,62 (d, J=13.3-inch, 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 header connection receive in accordance with the method of example 259, step D using piperidine-2-ylmethanol. MS (ESI): mass calculated for C20H22N2O2S, 354,1; found m/z 355,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,98 (d, J=7,2, 1H), 7,74 (d, 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 (d, J=14,1, 1H), 3.75 to the 3.65 (m, 1H), 3,56-of 3.46 (m, 1H), 3,37 (d, J=3,8, 1H), 2,72 (d, J=11,9,1H), of 2.36 (d, 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 header connection receive in accordance with the method of example 259, step D using (R)-pyrrolidin-2-ylmethanol. MS (ESI): mass calculated for C19H20N2O2S, 340,1; found m/z 340,1 [M+H]+.

1H NMR (400 MHz, DMSO-d6): of 7.97 (d, J=7,2, 1H), 7,73 (d, 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 (d, J=13,4, 1H), 3,55-of 3.48 (m, 1H), 3,42 (d, J=13,4, 2H), 2,84 (t, J=6,6, 1H), 2,68-2,58 (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 header connection receive in accordance with the method of example 259, step D using azetidin. MS (ESI): mass calculated for C17H16N2OS, 296,1; found m/z 297,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,80 (d, J=8,5, 1H), 7,56 (d, J=8,0, 1H), 7,35-of 7.24 (m, 5H), 7,19 (t, J=7,3, 1H), 3.43 points (c, 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 header connection receive in accordance with the method of example 259, step D using [1,4']diazepan-5-it. MS (ESI): mass calculated for

With19H19N3O2S, 353,1; found m/z 354,3 [M+H]+.

<> 1H NMR (400 MHz, DMSO-d6): 7,94 (d, J=7,9, 1H), 7,69 (d, 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 (c, 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 header connection receive in accordance with the method of example 259, step D using piperidine-3-ylmethanol. MS (ESI): mass calculated for C20H22N2O2S, 354,1; found m/z 355,3 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,98 (d, J=7,2, 1H), 7,74 (d, 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 (d, J=3,4, 2H), 3,36 be 3.29 (m, 1H), 3.27 to 3,18 (m, 1H), 2,92 (d, J=8,1, 1H), 2,77 (d, J=10,8, 1H), 1,96 (d, 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

Specified in the header connection receive in accordance with the method of example 259, step D using amide piperidine-3-carboxylic acid. MS (ESI): mass calculated for C20H21N3O2S, 367,1; found m/z 368,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): of 7.70 (d, J=7,8, 1H), 7,46 (d, J=8,0, 1H), 7,25-7,00 (m, 7H), 6,53 (c, 1H), 3,26 (d, J=2,9, 2H), 2.57 m (d, 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 (d, 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-ylox is)benzyl]-3,9-diazaspiro[5.5]undecane-3-carboxylic acid

Specified in the header connection receive in accordance with the method of example 259, step D, using tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid. MS (ESI): mass calculated for C28H35N3O3S, 493,2; found m/z of 494.5 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,13 (d, J=7,9, 1H), 7,89 (d, J=8,0,1H), 7.68 per-7,56 (m, 5H), 7,53 (t, J=7,1, 1H), 3,70 (c, 2H), 3,51 is-3.45 (m, 4H), 2,60-of 2.50 (m, 4H), of 1.66 (t, J=5,3, 4H), 1,58 (c, 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 header connection receive in accordance with the method of example 259, step D using 2-piperidine-3-retinol. MS (ESI): mass calculated for C21H24N2O2S, 368,2; found m/z 369,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 7,71 (d, J=8,4, 1H), 7,47 (d, 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 header connection receive in accordance with the method of example 262, step B, using CIS-4-aminocyclohexanecarboxylic acid. MS (ESI): mass calculated for C22H24N2O3S, 396,2; found m/z 397,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 9,15, (c, 1H), of 7.75 (d, J=7,6, 1H), 7,72 (DD, J=8.0 a, 0,7, 1H), 7,43 (dt, J=7,2, 1,2, 1H), 7,37-7,29 (m, 5H), 5,10 (users, 1H), 3,29 (users, 2H), 3,10 (t, J=7,4, 3H), 2,73 (users, 1H), 2,24 (userd, J=10,6, 2H), 2,09 (userd, 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 get according to example 262, step 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) with a solution of 50% triftormetilfullerenov acid in CH2Cl2(35 ml) is stirred at 23º C for 4 h, the Reaction mixture was concentrated and the residue suspended in diethyl ether, filtered and dried, obtaining mentioned in the title compound as a white solid (5.4 g, yield 94%). MS (ESI): exact mass calculated for C19H21N3OS, 339,1; found m/z 340,4 [M+H]+.

1H NMR (400 MHz, D6-DMSO): 9,50-of 9.30 (users, 1H), 7,94 (DD, J=7,9, 0,6, 1H), 7,68 (d, J=7,6 Hz, 1H), of 7.48-7,41 (m, 5H), 7,39-7,30 (m, 1H), 4,15-3,50 (users, 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).

B.(4-{2-[4-(Benzothiazol-2-yl) - Rev. XI)phenyl]ethyl}piperazine-1-yl)-(tetragidrofuran-2-yl)methanon

Specified in the header connection receive in accordance with the method of example 257, step C, using tetrahydrofuran-2-carboxylic acid and triethylamine. MS (ESI): mass calculated for C24H27N3O3S, 437,2; found m/z 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 (c, 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) is treated with NaH (14 mg, 0.6 mmol) and isopropylacetanilide (86 mg, 0.6 mmol) and the reaction mixture was stirred at 60ºC for 16 hours, the Reaction mixture was cooled, quenched by addition of CH3OH (5 ml) followed by addition of H2O (5 ml) and then adjusted the pH of the mixture to pH 7. The solution is extracted with ethyl acetate (2×25 ml) and an ethyl acetate solution is washed with 1M NaOH (2×30 ml). United podelochnye flush neutralized by adding 2M HCl and extracted with chloroform (2×30 ml). Solutions of chloroform, dried over Na2SO4filter and concentrate under reduced davleniyeni the crude product is purified on SiO 2(4 g, 0-10% 2M NH3/CH3OH:CH2Cl2), getting mentioned in the title compound as a solid (45 mg, yield 18%). MS (ESI): exact mass calculated for C24H29N3O5S2, 503,2; found m/z 504,5 [M+H]+.

1H NMR (400 MHz, C6D6): to 7.77 (d, J=7,8, 1H), 7,20 (DD, J=8.0 a, 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 (d, J=8,8, 1H), 6,13 (c, 1H), 3,98 (users, 2H), 3,51 (septet, J=6,8, 2H), 3,20 (users, 2H), 2,82 (users, 1H), 2,37 is 2.00 (m, 4H), 1,96-of 1.84 (m, 2H), 1,33 (d, 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) is treated with triethylamine (0.25 ml, 1.8 mmol) followed by the addition of METHYLCHLOROSILANE (of 0.07 ml, 0.8 mmol) and the reaction mixture was stirred at 23º C for 20 min, the Reaction mixture was diluted with CH2Cl2(10 ml) and washed with saturated aqueous NaHCO3(10 ml). The organic layer is dried over Na2SO4, filtered and concentrated under reduced pressure, obtaining mentioned in the title compound (234 mg, yield 99%). MS (ESI): exact mass calculated for C22H23N3O4S, 425,1; found m/z 426,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, J=7,6, 05, 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 (c, 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

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

Specified in the header connection receive in accordance with the method of example 34, step B, using benzosulfimide. MS (ESI): mass calculated for

With27H27N3O4S2, 521,1; found m/z 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 (users, 1H), 3,41-to 3.34 (m, 2H), 3,14 are 2.98 (m, 3H), 2,60 (users, 1H), 2,08 (userd, J=13,6, 2H), 1,86 (users, 2H) 1,30 (users, 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 header connection receive in accordance with the method of example 34, step B, using methanesulfonamide. MS (ESI): exact mass calculated for C22H25N3O4S2, 459,1; found m/z 460,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,81 (d, J=7,8, 1H), 7.62mm (d, 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 (userd, J=10,4, 1H), 3,48 is 3.40 (m, 2H), 3.33 and (c, 3H), 3,28 (c, 2H), 3,20 totaling 3.04 (m, 3H), 2,70-2,60 (m, 1H), 2,21 (userd, 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 header connection receive in accordance with the procedure of example 253, step D. MS (ESI): exact mass calculated for C21H21N3O4S, 411,1; found m/z 412,3 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.75 (t, J=8,3, 2H), of 7.70 (dt, J=8.0 a, 0,8, 1H), 7,28-7,22 (m, 5H), 4,28-3,88 (osirm, 4H), to 3.58-3,20 (osirm, 6H), and 3.16-3.04 from (users, 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 A (268 mg, 0.47 mmol) in CH2Cl2(6 ml) is treated with PS-dimethylamino resin (1.3 g, 0.90 mmol) followed by addition of 4-morpholinylcarbonyl (of 0.07 ml, 0.6 mmol) and the reaction mixture is subjected to shaking for 1 h, the Reaction mixture was treated with PS-isocyanate resin to remove excess isocyanate in 15 min the reaction mixture was filtered and concentrated, obtaining mentioned in the title compound (225 mg, yield 99%). MS (ESI): exact mass calculated for C24H28N4O3S, 452,2; found m/z 453,3 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (DD, J=8.0 a, 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 (ushort, 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 (users, 4H).

EXAMPLE 314

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

Specified in the header connection receive in accordance with the method of example 312, using 2-thiopheneacetyl. MS (ESI): exact mass calculated for C25H25N3O3S2, 463,1; found m/z rub464.3 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.77 (DD, J=8.0 a, 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 (d, 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 header connection receive in accordance with the method of example 313 using the hydrochloride of 2-nicotinoid. MS (ESI): exact mass calculated for C25H24N4O2S, 444,2; found m/z 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 (users, 2H), 3,52 (users, 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 (users, 2H).

EXAMPLE 316

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

Specified in the header connection receive in accordance with the method of example 313 using cyclopropanecarboxylate. MS (ESI): exact mass calculated for C23H25N3O2S, 407,2; found m/z 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 (d, J=16,0, 4H), 2,89 (DD, J=9,4, 6,5, 2H), 2,70 (DD, J=9,4, 6,5, 2H), 2,58 (userd, J=20,8, 4H), 1,78 (TT, J=8.0 a, 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 CH2Cl2(14 ml) is treated with PS-dimethylamino resin (740 mg, 1.0 mmol) and the reaction mixture is subjected to shaking for 1 h, the Resin is filtered off and the resulting solution of the free base is treated methoxybutanol acid (0.04 ml, 0.5 mmol) and PS-carbonyldiimidazole resin (500 mg, 0.6 mmol) and the reaction mixture is subjected to shaking for 1 h, the Reaction mixture was filtered, concentrated and the crude product was then purified on SiO2(12 g, 0-10% 2M NH3/MeOH:CH2Cl2), getting mentioned in the title compound (143 mg, yield 99%). MS (ESI): exact mass calculated for C22H25N3O2S, level of 414.2; m/z found, 412,4 [MH] +.

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 (c, 2H), and 3.72 (t, J=4,8, 2H), to 3.58 (t, J=4,8, 2H), 3,47 (c, 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 header connection receive in accordance with the method of example 317 using triftormetilfullerenov acid. MS (ESI): exact mass calculated for C21H20F3N3O2S, 435,1; found m/z 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 (c, 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 header connection receive in accordance with the method of example 262, step A, using onomatology ester of terephthalic acid, and example 250, step D. MS (ESI): exact mass calculated for C27H25N3O4S, 487,2; found m/z 488,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 8,00 (d, J=8,3, 2H), to 7.93 (DD, J=8.0 a, 0,8, 1H), 7,69 (DD, J=8.0 a, 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 (users, 2H), 3,30 (users, 2H), 2,88 (DD, J=7,0, 7,0, 2H), 2,60 (DD, J=8,3, 8,3, 2H), 2,55 (users, 2H), 244 (users, 2H).

EXAMPLE 320

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

Specified in the header connection receive in accordance with the method of example 317 using isonicotinoyl acid. MS (ESI): exact mass calculated for C25H24N4O2S, 444,2; found m/z 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 (users, 2H), 3,44 (ushort, 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 header connection receive in accordance with the method of example 317 using 5-methylpyrazine-2-carboxylic acid. MS (ESI): exact mass calculated for C25H25N5O2S, 444,21; found m/z 445,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 8,89 (d, J=1,4, 1H), 8,45 (d, J=1,0, 1H), 7,76 (DD, J=8,1, 0,5, 1H), of 7.70 (DD, J=8.0 a, 0,8, 1H), 7,43 (dt, J=7,4, 1,3, 1H), 7,33-7,28 (m, 5H), 3,90 (ushort, J=4,7, 2H), of 3.77 (ushort, J=4,8, 2H), 2,92 (DD, J=the 10.5 and 6.5, 2H), 2,80-of 2.72 (m, 2H), 2,69-of 2.64 (m, 2H), 2,66 (c, 3H).

EXAMPLE 322

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

Specified in the header of the connection get back in the availa able scientific C to the method of example 317, using 5-(R)-tetrahydrofuran-2-carboxylic acid. MS (ESI): exact mass calculated for C24H27N3O3S, 437,2; found m/z 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 (c, 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 header connection receive in accordance with the method of example 317 using 5-(S)-tetrahydrofuran-2-carboxylic acid. MS (ESI): exact mass calculated for C24H27N3O23S, 437,2; found m/z 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), with 3.89 (DDD, J=7,7, 7,5, 5,8, 1H), 3,82-and 3.72 (m, 2H), 3,76 (c, 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 header connection receive in accordance with the method of example 317 using 5-tetrahydrofuran-3-carboxylic acid. MS (ESI): exact mass calculated for C24 H27N3O3S, 437,2; found m/z 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 a, 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 header connection receive in accordance with the method of example 317 using glycolic acid. MS (ESI): exact mass calculated for C21H23N3O3S, 397,2; found m/z 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 a, 0,7, 1H), 7,43 (dt, J=7,5, 1,3, 1H), 7,35-7,28 (m, 5H), 4,21 (c, 2H, in), 3.75 (t, J=5,0, 2H), 3,68 (users, 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 header connection receive in accordance with the method of example 317 using 5-(2-oxocyclopent)acetic acid. MS (ESI): exact mass calculated for C26H29N3O3S, 463,2; found m/z 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-(4-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperazine-1-yl)propionic acid

Specified in the header connection receive in accordance with the method of example 262, step A, using 3-piperazine-1-ylpropionic acid. MS (ESI): exact mass calculated for C21H23N3O3S, 411,2; found m/z 412,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,25 (users, 1H), 7,76 (DD, J=8.0 a, 0,5, 1H), 7,69 {DD, J=7,8, 0,6, 1H), 7,42 (dt, J=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 (c, 4H).

EXAMPLE 328

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

Specified in the header connection receive in accordance with the method of example 262, step A, using cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it, and of example 259, step A. MS (ESI): exact mass calculated for C23H25N3O3S, 423,2; found m/z 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), only 3.57 (t, J=8,1, 2H), 3,11 (userd, J=11.8 in, 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 header connection receive in accordance with the method of example 262, step A, using piperidine-4-Immortalis-3-one, example 260, step A. MS (ESI): exact mass calculated for C24H27N3O3S, 437,2; found m/z 438,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, J=8,0, 1H), of 7.70 (DD, J=7,9, 0,7, 1H), 7,42 (dt, J=7,4, 1,2, 1H), 7,33-7,28 (m, 5H), 4,57 (TT, J=11,9, 4,3, 1H), 4,23 (c, 2H), 3,91, (t, J=4,9, 2H), 3,34 (t, J=5,1, 2H), 3,12 (userd, 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 header connection receive in accordance with the method of example 17, step A, using piperidine-4-Immortalis-3-one, example 260, step A. MS (ESI): exact mass calculated for C24H27N3O4S, 453,2; found m/z 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 (c, 2H), 4,14 (t, J=5,6, 2H), 3,90 (t, J=5,0, 2H), to 3.33 (t, J=5,1, 2H), 3,12 (userd, J=11,7, 2H), 2,87 (t, J=5,7, 2H), 2,32 (DDD, J=11.8 in, 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)oxaz is lidin-2-he

Specified in the header connection receive in accordance with the method of example 17, step A, using cleaners containing hydrochloride salt of 3-piperidine-4-isoxazolidine-2-it, and of example 259, step A. MS (ESI): exact mass calculated for C23H25N3O4S, 439,2; found m/z 440,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (DD, J=8,1, 0,7, 1H), 7,69 (DD, J=8.0 a, 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 (userd, J=12,0, 2H), 2,87 (d, 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, step A (383 mg, 1.0 mmol) in CH2Cl2(10 ml) is treated with N-methylmorpholine (of 0.24 ml, 2.2 mmol) and cyanuric chloride (61 mg, 0.3 mmol) and the resulting solution was stirred for 1 h while processing the reaction mixture is About-benzylhydroxylamine, and stirred for 16 hours, the Reaction mixture was filtered through a layer of diatomaceous earth, concentrated and purified on SiO2(12 g, 0-10% 2M NH3/MeOH/CH2Cl2), getting mentioned in the title compound (81 mg, yield 17%). MS (ESI): exact mass calculated for C28H29N3O3S, 487,2; found m/z 488,5 [M+H]+.

1 H NMR (400 MHz, CDCl3): a 8.34 (users, 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 (users, 2H), 3,05 (userd, J=11,6, 2H), 2,85 (DD, J=10,6, 7,6, 2H), 2.63 in (DD, J=8.5 a, 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 header connection receive in accordance with the method of example 262, step A, using ethyl ether piperidine-4-luxusni acid, and example 250, step D. MS (ESI): exact mass calculated for C22H24N2O3S, 396,2; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CD3OD): a 8.34 (users, 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 (userd, J=6,1, 1H), 2,20-2,08 (users, 1H), 2,11 (userd, 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 header connection receive in accordance with the method of example 262, step A, using salt acetic acid (R)-4-hydroxy-1-piperidine-4-iparralde-2-it, and of example 261, step A. MS (ESI): exact mass calculated for C24H27N3O3S, 437,2; found m/z 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), 2,21-2,12 (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 header connection receive in accordance with the method of example 262, step A, using hydroxyamide piperidine-4-carboxylic acid. MS (ESI): exact mass calculated for C21H23N3O3S, 397,2; found m/z 398,43 [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 (users, 2H), 3,10-2,95 (m, 4H), 2,80-2,50 (osirm, 3H), 2.23 to-1,96 (osirm, 5H).

EXAMPLE 336

(S)-1-(1-{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)-4-hydroxypyrrolidine-2-he

Specified in the header connection receive in accordance with the method of example 262, step A, using salt acetic acid, (S)-4-hydroxy-1-piperidine-4-iparralde-2-it, and of example 261, step A, using (S)-4-bromo-3-hydroxybutyrate. MS (ESI): exact mass calculated for

With24H27N3O3S, 437,2; found m/z 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), of 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 methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid

Specified in the header connection receive in accordance with the method of example 262, step A, using tert-butyl ether piperidine-4-ylcarbamate acid. MS (ESI): exact mass calculated for C25H31N3O3S, 453,2; found m/z 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 (userd, J=6,6, 1H), 3,55 is-3.45 (m, 1H), 2,93 (userd, 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 (userd, J=11,1, 2H), 1,45 (c, 9H).

EXAMPLE 338

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

Specified in the header connection receive in accordance with the method of example 262, step A, using 4-foreperiod. MS (ESI): exact mass calculated for C20H21FN3OS, 356,1; found m/z 357,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (DD, J=8,1, 0,5, 1H), 7,65 (DD, J=8.0 a, 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 header is Obedinenie receive in accordance with the method of example 262, stage And using 4,4-deformability. MS (ESI): exact mass calculated for C20H20F2N3OS, 374,1; found m/z 375,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (DD, J=8,1, 0,6, 1H), 7,65 (DD, J=8.0 a, 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 header connection receive in accordance with the method of example 262, step A, using (R)-3-hydroxypyrrolidine. MS (ESI): exact mass calculated for C19H20N2O2S, 340,1; found m/z 341,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (DD, J=8.0 a, 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), of 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 is obtained from the compound of example 337, following the method of example 266, step B, and example 317. MS (ESI): exact mass calculated for C21H23N3O2S, 381,2; found m/z 382,43 [M+H]+.

1H NMR (400 MHz, CDCl3): 8,16 (c, 1H), 7,72 (d, 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 (who, 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 obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid (example 337), following the method of example 266, step B. the resulting amine hydrochloride (227 mg, of 0.58 mmol) in CH2Cl2(5 ml) is 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 is stirred for 16 hours, the Reaction mixture was diluted with CH2Cl2(25 ml) and washed with NaHCO3(30 ml). The organic layer is dried over Na2SO4filter and concentrate under reduced pressure. The crude substance is purified on SiO2(12 g, 0-10% [2M NH3] CH3OH/CH2Cl2), getting mentioned in the title compound (134 mg, yield 58%). MS (ESI): exact mass calculated for C21H24N4O2S, 396,2; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, 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 (c, 2H), 3,93 (userd, 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-(-{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 obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid (example 337) by removing the Boc group according to example 266, step B. receive Free base, suspending the hydrochloride of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine (1.3 g, 3.3 mmol) in

CH2Cl2(20 ml) and washing with a solution of saturated NaHCO3(20 ml). The organic layer is dried over Na2SO4, filtered and concentrated under reduced pressure, obtaining 1.0 g (yield 83%) of free base, 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine. A solution of 1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-ylamine (145 mg, 0.4 mmol) in ethanol (5 ml) is treated with diphenylcyanoarsine (319 mg, of 1.34 mmol) and heated to 80ºC for 16 hours, the Reaction mixture was concentrated under reduced pressure and purified on SiO2(12 g, 0-10% [2M NH3CH3OH]/CH2Cl2), getting mentioned in the title compound (173 mg, yield 85%). MS (ESI): exact mass calculated for C28H27N5O2S, 496,2; found m/z 498,4 [M+H].

1H NMR (400 MHz, CDCl3): 7,73 (d, 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 (userd, J=6,5, 1H), a 3.87 is 3.76 (m, 1H), 3,02 (userd, J=11,2, 2H), and 2.83 (DD, J=8,4, 7,3, 2H), 2,64 (DD, J=8,6, 5,4, 2H), of 2.21 (t, J=11,1, 2H), 2,07 (d, J=11,0, 2), of 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 obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid (example 337) by removing the Boc group according to example 266, step B. receive Free base according to 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) is treated with dimethyl-N-cyanodithioiminocarbonate (180 mg, of 1.34 mmol) and heated to 80ºC for 16 hours, the Reaction mixture was concentrated under reduced pressure and purified on SiO2(12 g, 0-10% 2M NH3/CH3OH/CH2Cl2), getting mentioned in the title compound (143 mg, yield 69%). MS (ESI): exact mass calculated for C23H25N5OS2, 451,2; found m/z 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 (userd, J=196, 2H), 2,97 (userd, J=12,0, 2H), 2,82 (DD, J=10,3, 7,3, 2H), 2,62 (DD, J=8.5 a, 5,5, 2H), 2,60-2,44 (users, 3H), 2,18 (t, J=11,5, 2H), 2,03 (d, 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]those who}piperidine-4-ylamine obtained from tert-butyl methyl ether (1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}piperidine-4-yl)carbamino acid (example 337) by removing the Boc group according to example 266, stage B. receive Free base according to example 343. The free base (240 mg, of 0.68 mmol) in CH2Cl2(7 ml) is treated with triethylamine (142 μl, 1.0 mmol), then methanesulfonanilide (77 μl, 1.0 mmol) and the solution stirred for 16 hours, the Reaction mixture was diluted with CH2Cl2(20 ml) and washed with a solution of NaHCO3(30 ml). The organic layer is dried and concentrated under reduced pressure, then purified on SiO2(12 g, 0-10% 2M NH3/MeOH:CH2Cl2)to give 168 mg (yield 57%) specified in the connection header. MS (ESI): exact mass calculated for

With21H25N3O3S2, 431,1; found m/z 432,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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), 4,45 (d; J=7,6, 1H), 3,42-of 3.31 (m, 1H), 2,99 (c, 3H), 2,93 (userd, 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 (d, 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) is treated with a solution of 40% methylamine in water (0.2 ml) and the solution stirred at 80ºC for 1 h, the Reaction mixture was cooled to 23ºC and concentrated under reduced pressure, getting neocidin the th product which is purified on SiO2(4 g, 0-10% 2M NH3/MeOH:CH2Cl2), receiving 50 mg (yield 76%) specified in the connection header. MS (ESI): exact mass calculated for C23H26N6OS, 434,2; found m/z 435,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, 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 (users, 1H), 4.75 in (users, 1H), 3,63 (users, 1H), 2,94 (userd, J=11,9, 2H), 2,86 (d, J=4,9, 2H), 2,82 (DD, J=10,4, 7,4, 2H), 2,61 (DD, J=8.5 a, 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-diazaspiro[4.5]Decan-4-one

Specified in the header connection receive in accordance with the method of example 262, step A, using 1-phenyl-1,3,8-diazaspiro[4.5]Decan-4-one. MS (ESI): exact mass calculated for C28H28N4O2S, 484,2; found m/z 485,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (DD, J=8.0 a, 0,5, 1H), 7,66 (DD, J=7,9, 0,7, 1H), 7,52 (c, 1H), 7,42 and 7.36 (m, 1H), 7,34-7,24 (m, 6H), 6,91 (d, J=8,0, 1H), 6.87 in (t, J=7,3, 1H), 4.75 in (c, 2H), 2.95 and-to 2.85 (m, 4H), was 2.76-of 2.66 (m, 4H), of 1.76 (d, J=13,9, 2H).

EXAMPLE 348

8-{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}-1,3,8-diazaspiro[4.5]decane-2,4-dione

Specified in the header connection receive in accordance with the method of example 262, step A, using 1,3,8-diazaspiro[4.5]decane-2,4-dione. MS (ESI): exact mass calculated for C22H22N4O3 S, 422,1; found m/z 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=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-of 2.10 (m, 2H), 1,75 (d, 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 header connection receive in accordance with the method of example 262, step A, using tert-butyl ether, methylpiperidin-4-ylcarbamate acid. MS (ESI): exact mass calculated for

With26H23N3O3S, 467,2; found m/z 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 (osirm, 1H), of 3.07 (d, J=11,6, 2H), and 2.83 (DD, J=11,1, 7,8, 2H), 2,75 (c, 3H), 2,61 (d, 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 (c, 9H).

EXAMPLE 350

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

Specified in the title compound is obtained from the compound of example 349, following the example 266, step B, example 343 and example 345, using acetylchloride. MS (ESI): exact mass calculated for C23H27N3O2S, 409,2; found m/z 410,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (DD, J=8,1, 0,6, 1H), 7,66 (DD, J=8.0 a, 1,1, 1H), 7,41 and 7.36 (m, 1H), 7,31-7,25 (who, 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 is obtained from the compound of example 349, following the example 266, step B, example 343 and example 345, using methanesulfonanilide. MS (ESI): exact mass calculated for C25H29N3O4S, 467,2; found m/z 468,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (l, 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 (c, 3H), 2,82 (c, 3H), 2,83-and 2.79 (m, 2H), 2,61 (DD, J=8,5 that 5.3, 2H), 2,18 (DDD, J=11.8 in, 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 title compound is obtained from the compound of example 349, following the example 266, step B, example 343 and example 345, using chlorocarbonylsulfenyl ester of acetic acid. MS (ESI): exact mass calculated for C23H27N3O2S, 467,2; found m/z 468,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (DD, J=8,1, 0,5, 1H), 7,66 (d, J=7,9, 1H), 7,42 and 7.36 (m, 1H), 7,29-of 7.24 (m, 5H), 4,76 (c, 0,6H), 4,71 (c, 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, H), 2,19 (c, 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 is obtained from the compound of example 337, following the example 266, step B, example 343 and example 345, using acetylchloride. MS (ESI): exact mass calculated for C25H29N3O4S, 395,2; found m/z 396,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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), of 5.48 (d, 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 (d, 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

Specified in the title compound is obtained from the compound of example 337 according to example 266, step B, example 343 and example 354 using chlorocarbonylsulfenyl ester of acetic acid. MS (ESI): exact mass calculated for C24H27N3O4S, 453,2; found m/z 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), 4,54 (c, 2H), 3.96 points-of 3.85 (m, 1H), 3,00 (d, 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 (c, 3H), 1,98 (d, 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 header connection receive according to the method of example 262, step A, using (S)-3-(1H-imidazol-2-yl)-2-methylaminopropane acid. MS (ESI): exact mass calculated for C22H22N4O3S, 422,1; found m/z 423,3 [M+H]+.

1H NMR (400 MHz, CD3OD): cent to 8.85, (c, 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 (d, J=8,6, 2H), is 3.08 (c, 3H).

EXAMPLE 356

2-(4-{2-[4-(3-Nitropyridine-2-yl)-[1,4]diazepan-1-yl]ethyl}phenoxy)benzothiazole

Specified in the header connection receive according to the method of example 262, step A, using 1-(3-nitropyridine-2-yl)-[1,4]diazepan. MS (ESI): exact mass calculated for C25H25N5O3S, 475,2; found m/z 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 a, 0,7, 1H), 7,45-7,40 (m, 1H), 7,29-of 7.24 (m, 5H), was 6.73 (DD, J=8.0 a, 4,4, 1H), 3,80-3,75 (users, 2H), 3,47-3,40 (users, 2H), 3,07-3,01 (users, 2H), 2.95 and-is 2.88 (m, 2H), 2,86-and 2.79 (m, 4H), 2,20-2,10 (users, 2H).

EXAMPLE 357

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

Specified in the header connection receive according to the method of example 251, step B, using piperidine. MS (ESI): mass calculated for C 19H20N2OS, 324,4; found m/z 325,3 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.75 (d, J=8,2, 1H), 7,73 (d, J=8,2, 1H), was 7.36-7,42 (m, 3H), 7.24 to to 7.32 (m, 3H), 3,49 (c, 2H), 2,39 (users, 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 header connection receive according to the method of example 251, step B, using 4-phenylpiperidine-4-ol. MS (ESI): mass calculated for C25H24N2O2S, 416,5; found m/z 417,4 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.75 (d, J=8,0, 1H), 7,66 (d, J=8,0, 1H), 7,55-7,51 (m, 2H), 7,47-7,25 (m, 9H), 3,63 (c, 2H), 2,85-2,77 (m, 2H), 2,50 (dt, J=11.8 in, 2,5, 2H), 2,18 (dt, J=13,0, 4,4, 2H), 1,80-of 1.74 (m, 2H), 1.55V (users, 1H).

EXAMPLE 359

1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-ol

Specified in the header connection receive according to the method of example 251, step B, using 4-piperidinol. MS (ESI): mass calculated for C19H20N2O2S, 340,4; found m/z 341,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (c, 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 header connection receive according to the method of example 251, step B, using Pieper is DIN-4-ylmethanol. MS (ESI): mass calculated for C20H22N2O2S, 354.5 TWh excluding; found m/z 355,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), to 7.67 (d, J=8,0, 1H), 7,42-7,37 (m, 3H), 7,32-7,25 (m, 3H), 3,54 (c, 2H), 3,51 (d, J=6,5, 2H), 2,97-2,90 (m, 2H), 2,01 (dt, J=11,6, 2,4, 3H), 1,73 (d, 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}methanesulfonamide

Specified in the header connection receive according to the method of example 253, stages a and b, and then example 258, step C. MS (ESI): mass calculated for C20H23N3O3S2, 417,6; found m/z 418,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), 7,68 (d, 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 (c, 2H), 3.43 points-of 3.32 (m, 1H), 2,99 (c, 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

N-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido

Specified in the header connection receive according to the method of example 258, stages a and b, and then of example 253, step C, using glycolic acid. MS (ESI): mass calculated for C22H25N3O3S, 411,5; found m/z 412,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (c, 2H), 3,51 (c, 2H), 3,24 (t, J=6,3, 2H), 2,88-to 2.94 (m, 2H), 2,20 (d, J=11,5, 1H), 2,02-of 1.92 (m, 2H), 1,72-1,65 (m, 2H), 1,62 of 1.50 (m, 2H), 1,36-of 1.26 (m, 2H).

EXAMPLE 363/p>

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

Specified in the header connection receive according to the method of example 253, stages a and b, and then example 258, step C, using methyl isocyanate. MS (ESI): mass calculated for C21H23N3O3S, 397,5; found m/z 398,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (users, 1H), 3,66 (c, 3H), 3,51 (c, 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 header connection receive according to the method of example 258, phase a, b and C, using trimethylsilyltriflate. MS (ESI): mass calculated for

With21H24N4O2S, 396,5; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (users, 1H), 4,35 (c, 2H), 3,50 (c, 2H), 3,07 (ushort, 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 1.44MB (c, 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 header connection receive according to the method of example 258, stages a and b, and example 257, step C, using triperoxonane acid. MS(ESI): mass, calculated for C22H22F3N3O2S, 449,5; found m/z 450,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 (users, 1H), 3,51 (c, 2H), or 3.28 (t, J=6,46, 2H), 2,92 (d, J=11,5, 2H), 2,02-of 1.94 (m, 2H), 1,74-and 1.54 (m, 3H), 1,38-1.27mm (m, 2H).

EXAMPLE 366

{4-[4-(Benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid

Specified in the header connection receive according to the method of example 259, stage C and D, and example 250, step D, using piperazine-1-luksusowe acid. MS (ESI): mass calculated for C20H21N3O3S, 383,5; found m/z 384,4 [M+H]+.

1H NMR (400 MHz, CD3OD): to 7.77 (d, J=8,0, 1H), 7.62mm (d, J=8,0, 1H), 7,50-7,46 (m, 2H), 7,42-7,26 (m, 4H), 6,67 (c, 2H), 3,60 (c, 2H), 3,34 (users, 4H), 2,77 (users, 4H).

EXAMPLE 367

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

Specified in the header connection receive according to the method of example 257, stages a and b, and example, step C. MS (ESI): mass calculated for C19H21N3O3S2, 403,53; found m/z 404,3 [M+H]+.

1H NMR(400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), 7,68 (d, J=8,0, 1H), 7,42 and 7.36 (m, 3H), 7,35-7,26 (m, 3H), 3,57 (c, 2H), 3,26 (ushort, J=4,7, 4H), 2,79 (c, 3H), 2,58 (ushort, J=4,7, 4H).

EXAMPLE 368

1-{4-[4-(Benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline

p> Specified in the header connection receive according to the method of example 257, phase a, b and C, using triperoxonane acid. MS (ESI): mass calculated for C20H18F3N3O2S, 421,44; found m/z 422,43 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), 7,68 (d, J=8,0, 1H), 7,42-7,27 (m, 6H), 3,74-3,70 (m, 2H), 3,65-of 3.60 (m, 2H), 3,57 (c, 2H), 2,56-of 2.50 (m, 4H).

EXAMPLE 369

2-(4-(Morpholine-4-ylmethylene)benzothiazole

Specified in the header connection receive according to the method of example 259, stage C and D, using morpholine. MS (ESI): mass calculated for C18H18N2O2S, 326,42; found m/z 327,4 [M+H]+.

1H NMR (500 MHz, CDCl3): 7,74 (d, 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 (c, 2H), 2,46 (users, 4H).

EXAMPLE 370

Phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the header connection receive according to the method of example 253, stages a and b, then example 258, step C, using phenylisocyanate. MS (ESI): mass calculated for C26H25N3O3S, 459,57; found m/z 460,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), to 7.67 (d, J=8,0, 1H), 7,42-7,10 (m, 11H), 4,95 (userd, J=7,8, 1H), 3,67-to 3.58 (m, 1H), 3,53 (c, 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 header connection receive according to the method of example 253, stages a and b, and then example 258, step C, using benzosulphochloride. MS (ESI): mass calculated for C25H25N3O3S2, 479,62; found m/z 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 (userd, J=7,8, 1H), 3,48 (c, 2H), 3,26-and 3.16 (m, 1H), was 2.76 of 2.68 (m, 2H), 2.06 to of 1.97 (m, 2H), 1,78-1,70 (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 header connection receive according to the method of example 251, stages a and b, using ethyl ester 3-aminopropionic acid. MS (ESI): mass calculated for C19H20N2O3S, 356,45; found m/z 357,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,0, 1H), to 7.67 (d, J=8,0, 1H), 7,44-7,25 (m, 6H), 4,21 (users, 1H), 4,15 (kV, J=7,2, 2H), a 3.87 (c, 2H), 2.95 points (t, J=6,3, 2H), 2,58 (t ,7=6,3, 2H), 1.26 in (t, J=7,2, 3H).

EXAMPLE 373

3-[4-(Benzothiazol-2-yloxy)benzoylamino]propionic acid

Specified in the header connection receive according to the method of example 372 and the sample stage 250 D. MS (ESI): mass calculated for C17H16N2O3S, 328,39; found m/z 329,3 [M+H]+.

H NMR (400 MHz, DMSO): 7,87 (d, J=8,0, 1H), 7.62mm (d, J=8,0, 1H), 7,44-of 7.23 (m, 6H), of 3.77 (c, 2H), 2,72 (t, J=6,6, 2H), to 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 header connection receive according to the method of example 18 stage A, and example 20, using the ethyl ester of 3-methylaminopropane acid. MS (ESI): mass calculated for C26H31N3O5S, 497,62; found m/z 498,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,0, 1H), 7,65 (d, 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), 3,12 (c, 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 connection receive according to the method of example 9 and example 24, using ethyl ether [1,4']bipyridinyl-4-carboxylic acid. MS (ESI): mass calculated for C28H35N3O4S, 509,67; found m/z 510,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,0, 1H), 7,65 (d, 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 header connection receive according to the method of example 376 and example 250, step D. MS (ESI): mass calculated for C26H31N3O4S, 481,62; found m/z 482,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, 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) in CH2Cl2(156 ml) was stirred at room temperature for 1 h To the obtained mixture is added NaBH(OAc)3(6,61 g, and 31.2 mmol). The mixture is stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(200 ml), washed with 1N. NaOH (3×50 ml) and concentrate under reduced pressure, obtaining the crude product as a yellow oil. The crude product is purified on SiO2(330 g; 0-10% CH3OH/CH2Cl2), getting a clear oil, which crystallized upon standing (3.4 g, o is d 71%). MS (ESI): mass calculated for C18H18N2OS, 310,11; found m/z 311,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,76 (d, J=8,1, 1H), 7.62mm (d, 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).

B.{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 h To the obtained mixture is added NaBH(OAc)3(of 1.02 g, 4.8 mmol). The mixture is stirred at room temperature for 24 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(100 ml) and concentrate under reduced pressure, obtaining the crude product as a yellow oil. The crude product is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2), getting a clear oil (465 mg, yield 86%). MS (ESI): mass calculated for C20H22N2OS, 338,15; found m/z 339,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,66 (d, J=8,1, 1H), 7,58 (d, J=8,1, 1H), 7,31 (t, J=8,1, 1H), 7.23 percent-to 7.15 (m, 5H), 2,80 (c, 4H), of 2.72 (DD, J=7,3, 7,1, 2H), 1,78 is 1.70 (m, 1H), of 1.05 (t, J=7,1, 3H), 0.50 to 0,36 (m, 4H).

EXAMPLE 379

Salt triftormetilfullerenov acid 3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)-2-methylpropionic acid

A.Methyl ester 3-({2-[4-(benzothiazol-2-yloxy)is enyl]ethyl}cyclopropylamino)-2-methylpropionic acid

To a solution of {2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamine (500 mg, 1.6 mmol) in CH3CN (10 ml) at room temperature add N,N-diisopropylethylamine (349 μl, 2 mmol) followed by the addition of a methyl ether, 3-bromo-2-methylpropionic acid (362 mg, 2 mmol). The resulting mixture was heated at 60ºC overnight. The mixture is cooled and dissolved in CH2Cl2(100 ml), washed with saturated aqueous NaHCO3(1×25 ml), and

H2About (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 is purified on SiO2(40 g; 0-10% CH3HE/CH2Cl2), receiving not quite pale white solid (158 mg, yield 39%). MS (ESI): mass calculated for C23H26N2O3S, 410,17; found m/z 411,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,73 (d, J=8,3, 1H), 7,65 (d, J=8,3, 1H), 7,38 (t, J=8,1, 1H), 7,28-of 7.23 (m, 5H), 3,66 (c, 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 (d, J=7,1, 3H), 0,51-0,30 (m, 4H).

B. Salt triftormetilfullerenov acid 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 3:1 THF/CH3OH (13 ml) add a solution of the hydroxide is lithium (37 mg, 1.54 mmol) in H2About (3 ml). The reaction solution was stirred at room temperature for 16 h and then concentrated under reduced pressure. The residue is dissolved in CH3OH and purified HPLC with reversed phase. The desired fractions are collected and concentrated under reduced pressure, obtaining mentioned in the title compound as a clear oil (179 mg, yield 92%). MS (ESI): mass calculated for C22H24N2O3S, 396,15; found m/z 397,3 [M+H]+.

1H NMR (400 MHz, CD3OD): for 7.78 (d, 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 (d, 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 (d, 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 header connection receive according to the method of example 378, step A, using cyclopropanemethylamine, and (methodology) of example 379, step A, using 2-bromoethanol. MS (ESI): mass calculated for C21H24N2O2S, 368,16; found m/z 369,3 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.70 (d, J=8,1, 1H), 7.62mm (d, 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

is shown in the header connection receive according to the method of example 380. MS (ESI): mass calculated for C23H28N2O3S, 412,18; found m/z 413,3 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.64 (d, J=8,3, 2H), 7,41 (d, J=8,3, 2H), 7,31 (t, J=8,3, 1H), 7,25-7,17 (m, 3H), 4,08 (users, 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}cyclopropanemethylamine)propan-1-ol

Specified in the header connection receive according to the method of example 378, step A, using cyclopropanemethylamine, and example 379, step A, using 3-bromopropane-1-ol. MS (ESI): mass calculated for C22H26N2O2S, 382,17; found m/z 383,3 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.70 (d, J=8,1, 1H), 7.62mm (d, 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 (d, 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

Salt triftormetilfullerenov acid {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 2H-tetrazole (61 mg, 0.87 mmol) in CH2Cl2(12 ml) is added triphenylphosphine deposited on a polymeric substrate (290 mg, 0.87 mmol)and di-tert-utilisationbased (200 mg, 0.87 mmol). The reaction mixture was stirred at room is based temperature for 1 h, filtered and the collected solids washed with CH2Cl2(10 ml). The filtrate is concentrated under reduced pressure, obtaining the crude product as a pale yellow oil. The crude product was dissolved in CH3OH and purified HPLC with reversed phase. The desired fractions are collected and concentrated under reduced pressure, obtaining mentioned in the title compound as a clear oil (100 mg, yield 40%). MS (ESI): mass calculated for C23H26N6OS, 434,19; found m/z 435,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 8,75 (c, 1H), of 7.75 (d, J=8,1, 1H), 7,60 (d, 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 (d, J=7,3, 2H), to 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 header connection receive according to the method of example 379, step A, using 1-(3-bromopropyl)-1H-pyrrole. MS (ESI): mass calculated for C25H27N3OS, 417,19; found m/z 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 (t, 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), to 2.57 (t, J=7,1, 2H), 1,98-1,88 (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)Buti is ontril

Specified in the header connection receive according to the method of example 378, step A, using cyclopropanemethylamine, and of example 319, step A, using 4-bromobutyronitrile. MS (ESI): mass calculated for C23H25N3OS, 391,17; found m/z 392,3 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.70 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,35 (t, J=8,1, 1H), 7,27-7,20 (m, 5H), 2.77-to 2,73 (m, 4H), of 2.64 (t, J=6,6, 2H), 2,39 (d, J=6,3, 2H), to 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 header connection receive according to the method of example 33, step B, using 3-aminopropionitrile. MS (ESI): mass calculated for C24H26N4O2S, 434,18; found m/z 435,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, 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 add trimethylaluminum (2,0M solution in toluene, of 1.53 ml, is 3.08 shall mol) followed by the addition of azeotropically (404 μl, is 3.08 mmol). The resulting mixture was heated at 80ºC for 18 hours the Mixture is cooled to room temperature and diluted with CH2Cl2(200 ml), washed with saturated aqueous NaHCO3(1×25 ml) and H2About (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 is purified on SiO2(40 g; 0-20% CH3OH/CH2Cl2), receiving not quite white solid (246 mg, yield 88%). MS (ESI): mass calculated for C23H26N6OS, 434,19; found m/z 435,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,25 (users, 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), and 2.83 (d, J=7,3, 2H), 2,18-2,07 (m, 2H), 1,01-of 0.91 (m, 1H), 0,57-0,50 (m, 2H), of 0.25 to 0.18 (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 CH3CN (10 ml) at 0ºC add diisopropylethylamine (567 μl, is 2.88 mmol) and after 2 min add azidotimedine (399 μl, 3.04 from mmol) for 20 minutes the Reaction mixture allow to warm to room temperature for 30 min, then paramashiva the t for an additional 14 hours The reaction mixture was added to ice H2O (20 ml) and extracted with CH2Cl2(2×25 ml). The combined organic layers are dried (Na2SO4) and concentrate. The residue is purified on SiO2(40 g; 0-15% CH3OH/CH2Cl2), receiving not quite white solid (439 mg, yield 83%. MS (ESI): mass calculated for C24H25N7OS, 459,18; found m/z 460,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), 7,66 (d, 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, in), 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 header connection receive according to the method of example 387. MS (ESI): mass calculated for C20H24N6OS, 420,17; found m/z 421,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 13,02 (users, 1H), 7,50 (DD, J=8,1, 3,5, 2H), 7,20 (t, 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 header connection receive according to the method of example 33, steps In and using 2-amino-2-methylpropan-1-ol. MS (ESI): mass calculated for C25H31N3O3S, 453,21; ideno m/z 454,4 [M+H] +.

1H NMR (400 MHz, CDCl3): of 7.75 (d, J=8,1, 1H), 7,68 (d, J=8,1, 1H), 7,40 (t, J=8,1, 1H), 7,32-7,25 (m, 5H), of 5.83 (c, 1H), 5,06 (users, 1H), 3,59 (c, 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 (c, 6H).

EXAMPLE 391

Salt triftormetilfullerenov acid {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)butylmethacrylate

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) is treated by bubbling gaseous hydrogen chloride for 1 h, the resulting suspension is filtered and washed with ether, getting mentioned in the title compound (1.12 g, yield 92%). Due to the instability of the crude substance is used immediately without further purification.

B.Salt triftormetilfullerenov acid {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)butylmethacrylate (511 mg, 1 mmol) in ethanol (4.5 ml) is added triethylamine (375 μl, 2.7 mmol) with subsequent davleniem.dalee hydrazide formic acid (60 mg, 1 mmol) in ethanol (4.5 ml). The resulting mixture was stirred at room temperature for 2 h and then at the boiling point under reflux for 1 h the Mixture is cooled and diluted with CH2Cl2(1500 ml), washed with saturated aqueous NaHCO3(1×25 ml) and H2About (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 is purified on

SiO2(40 g; 0-15% CH3OH/CH2Cl2), receiving not quite white solid (317 mg, yield 73%). MS (ESI): mass calculated for C24H27N5OS, 433,19; found m/z 434,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to $ 7.91 (c, 1H), 7,68 (d, 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 (d, J=6,6, 2H), 2.00 in 1,90 (m, 2H), 0,93-of 0.82 (m, 1H), up 0,56 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 header connection receive according to the method of example 391, the stage In using acetic acid hydrazide. MS (ESI): mass calculated for

With25H29N5OS, 447,21; found m/z 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 (d, J=6,8, 2H), 2,37 (c, 3H), 2,07-1,9 (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 header connection receive according to the method of example 391, the stage In using benzoic acid hydrazide. MS (ESI): mass calculated for

With30H31N5OS, 509,22; found m/z 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 (d, 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 (d, 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

Salt triperoxonane acid 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) add K2CO3(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 CH3OH and purified HPLC with reversed phase. The desired fractions are collected and concentrated under reduced pressure, obtaining mentioned in the title compound as a colourless oil (289 mg, yield 27%). MS (ESI): mass calculated for C22H 24N6OS, 420,17; found m/z 421,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,72 (d, J=7,8, 1H), 7,58 (d, J=7,8, 1H), 7,44-7,28 (m, 5H), 7,25 (t, J=8,1, 1H), 4,06 (c, 3H), 3,80 (d, 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 header connection receive according to the method of example 394. MS (ESI): mass calculated for C22H24N6OS, 420,17; found m/z 421,3 [M+H]+.

1H NMR (400 MHz, CD3OD): of 7.75 (d, J=7,8, 1H), 7,60 (d, J=7,8, 1H), 7,46-7,33 (m, 5H), 7,28 (t, J=7,8, 1H), or 4.31 (c, 3H), 3,79 (d, 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 header connection receive according to the method of example 262, using piperidine-4-carbonitrile. MS (ESI): mass calculated for C21H21N3OS, 363,14; found m/z 364,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,63 (d, J=7,6, 1H), 7,55 (d, 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)piperidine-1-yl]ethyl}phenoxy)benzothiazole

To a solution of trimethylsilyldiazomethane (1.8 ml, 3.6 mmol) in diethyl ether (30 ml) at 0ºC in an atmosphere of nitrogen until ablaut dropwise n-utility (2.5m in hexane, the 1.44 ml, 3.6 mmol) and the reaction mixture was stirred at 0ºC 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 0ºC. The resulting mixture was stirred at 0ºC for 3 hours the Mixture was treated with saturated aqueous NH4Cl and extracted with CH2Cl2(2×100 ml). The extracts are washed with H2About (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 is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2), receiving not quite white solid (768 mg, yield 54%). MS (ESI): mass calculated for C22H23N5OS, 405,16; found m/z 406,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,63 (d, J=8,1, 1H), 7,56 (d, J=8,1, 1H), 7,42 (c, 1H), 7,29 (t, J=7,8, 1H), 7.23 percent-7,14 (m, 5H), 4,67 (users, 1H), 3.04 from (d, J=11,9, 2H), 2,84-2,70 (m, 3H), 2,63-of 2.56 (m, 2H), 2,16 (t, J=11,1, 2H), 1,97 (d, 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 header connection receive in accordance with the method of example 378, step A, using the ethyl ester of 4-aminobutyric acid. MS (ESI): mass calculated for C21H24N2O3S, 384,15; found m/z 385,3 [M+H]+.

H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,38 (t, J=8,1, 1H), 7,31-7,22 (m, 5H), 6,67 (users, 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), to 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}cyclobutylamine)butyric acid

Specified in the header connection receive according to the method of example 378, step A, using cyclopropanemethylamine, and example 379, step A, using 4-ethyl ester 4-pamakani acid. MS (ESI): mass calculated for

With25H30N2O3S, 438,20; found m/z 439,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,35 (t, J=8,1, 1H), 7,27-7,20 (m, 5H), 6,67 (users, 1H), 4,10 (DD, J=7,1, 7,1, 2H), 2,83-a 2.71 (m, 4H), 2,60 (t, 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 header connection receive according to the method of example 378, step A, using cyclopropanemethylamine, and example 379, step A, using 2-(3-bromopropyl)isoindole-1,3-dione. MS (ESI): mass calculated for C30H29N3O3S, 511,19; found m/z 512,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,84-to 7.77 (m, 2H), 7,72-7,63 (m, 3H), 7,60 (d, 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), to 2.65 (t, J=7,6, 2H), 2,39 (d, 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 is obtained from the compound of example 399, following the method of example 379, step C. MS (ESI): mass calculated for C23H26N2O3S, 410,17; found m/z 411,4 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,42 (d, J=7,8, 1H), 7,31 (d, 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), 2.91 in-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 header connection receive according to the method of example 378, step A, using 1-(3-aminopropyl)pyrrolidin-2-it. MS (ESI): mass calculated for C22H25N3O2S, 395,17; found m/z 396,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.67 (d, J=8,1, 1H), 7,60 (d, J=8,1, 1H), 7,32 (t, J=7,8, 1H), 7,28-to 7.15 (m, 5H), 5,61 (users, 1H), 3,34-of 3.25 (m, 4H), 2,94-of 2.81 (m, 4H), to 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-ylox is)phenyl]ethyl}cyclopropylamino)propyl]isoindole-1,3-dione (example 400, 3.0 g, 5,86 mmol) in EtOH (12 ml) is 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 NaHCO3(2×20 ml), H2About (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 is purified on SiO2(330 g; 0-10% 2M NH3in CH3OH/CH2Cl2), getting a clear oil (2,13 g, yield 96%). MS (ESI): mass calculated for C22H27N3OS, 381,2; found m/z 382,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to 7.68 (d, J=8,1, 1H), 7,58 (d, 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 (d, J=6,6, 2H), 2,07 (c, 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 header connection receive according to the method of example 379, step A, using methyl ester of 5-bromopentanoate acid. MS (ESI): mass calculated for C24H28N2O3S, 424,18; found m/z 425,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), was 7.36 (t, J=8,1, 1H), 7,27-7,20 (m, 5H), 3,65 (c, 3H), 2,85 is 2.80 (m, 4H), to 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 N1-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl)-N1-cyclopropylmethyl-1,3-diamine (example 403, 180 mg, 0.47 mmol) in CH2Cl2(10 ml), add triethylamine (131 μl, of 0.94 mmol) followed by addition of 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 NaHCO3(2×15 ml), H2About (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 is purified on SiO2(12 g, 0-10% CH3OH/CH2Cl2), getting a white solid (154 mg, yield 77%). MS (ESI): mass calculated for C24H29N3OS, 423,2; found m/z 424,4 [M+H]+.

1H NMR (400 MHz, CDCl3): RS 9.69 (users, 1H), to 7.67 (d, J=8,1, 1H), 7.62mm (d, 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 (d, J=6,8, 2H), 1,88 (c, 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 header connection receive is in accordance with the method of example 405, using morpholine-4-carbonylchloride. MS (ESI): mass calculated for C28H34N4O3S, 494,24; found m/z 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 (users, 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]methanesulfonamide

Specified in the header connection receive according to the method of example 405, using methanesulfonanilide. MS (ESI): mass calculated for C23H29N3O3S2, 459,17; found m/z 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 (users, 1H), 3.43 points-to 3.09 (m, 8H), 3,07 are 2.98 (m, 2H), 2,96 (c, 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 is obtained from the compound of example 379, following the method of example 404, step C. MS (ESI): mass calculated for C23H26N2O3S, 410,17; found m/z 411,3 [M+H]+.

1H NMR (400 MHz, CDCl3): KZT 12.39 (users, 1H), 7,71 (d, 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).

P the EMER 409

1-[3-({2-[4-(Benzothiazol-2-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), acetone (185 μl, 2,52 mmol) in CH2Cl2(25 ml) was stirred at room temperature for 1 h To the obtained mixture is added NaBH(OAc)3(536 mg, 2,52 mmol). The mixture is stirred at room temperature for 16 h, filtered through a layer of diatomaceous earth, washed with CH2Cl2(100 ml) and concentrate under reduced pressure, obtaining the crude product as a yellow oil. The crude product is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2). The desired fractions are combined and concentrated under reduced pressure, obtaining a clear oil, which crystallized upon standing (290 mg, yield 53%). MS (ESI): mass calculated for C25H31N3O2S, 437,21; found m/z 438,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,3, 1H), 7,66 (d, J=8,3, 1H), 7,38 (t, J=8,3, 1H), 7,28-of 7.23 (m, 5H), to 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 (d, J=6,8, 6H).

EXAMPLE 410

1-[3-({2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]pyrrolidin-2-he

Specified in the header connection receive is in accordance with the method of example 409, using cyclopropanecarboxaldehyde. MS (ESI): mass calculated for C26H31N3O2S, 449,21; found m/z 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), to 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), of 2.72 (d, 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 EtOH (20 ml) is 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 heated at the boiling point under reflux for 16 h, cooled and filtered through a layer of diatomaceous earth, washed with CH2Cl2(100 ml) and concentrate under reduced pressure, obtaining the crude product as a clear oil. The crude product is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2. The desired fractions are combined and concentrated under reduced pressure, obtaining white solid (434 mg, yield 66%). MS (ESI): mass calculated for C25H29N3O2S, 435,2; found m/z 436,4 [M+H] .

1H NMR (400 MHz, CDCl3): 7,72 (d, 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), or 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), 2,03-1,94 (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 header connection receive according to the method of example 409, using Propionaldehyde. MS (ESI): mass calculated for C25H31N3O2S, 437,21; found m/z 438,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,66 (d, 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), of 2.64 (t, J=7,6, 2H), 2,58 (t, J=7,6, 2H), 2,42-2,35 (m, 2H), 2,07-of 1.97 (m, 2H), 1,80-1,71 (m, 2H), 1,59 to 1.47 (m, 2H), 0,92 (d, 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 header connection receive according to the method of example 409, using 1-acetylpiperidine-4-one. MS (ESI): mass calculated for C28H35N3O4S, 509,23; found m/z 510,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,38 (t, J=8,1, 1H), 7,29-of 7.23 (m, 5H), 4,69 (d, J=13,1, 1H), 4,13 (DD, J=7,8, 6,8, 2H), 3,85 (d, 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 (c, 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-methylpiperidin-4-yl)-{2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}amino)butyric acid

Specified in the header connection receive according to the method of example 409, using 1-methylpiperidin-4-one. MS (ESI): mass calculated for C27H35N3O3S, 481,2; found m/z 482,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, 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 (d, J=12,1, 2H), 2,75-2,69 (m, 4H), 2,58-of 2.50 (m, 3H), 2,38 (c, 3H), to 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 is obtained from the compound of example 398, following the method of example 407 and example 379, step C. MS (ESI): mass calculated for C20H22N2O5S2, of 434.1; found m/z 435,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,38 (t, J=8,1, 1H), 7,33-of 7.24 (m, 5H), of 3.48 (t, J=7,6, 2H), 3,20 (t, J=7,6, 2H), 2,96 (t, J=7,3, 2H), 2,77 (c, 3H), is 2.37 (t, J=6,6, 2H), 1.91 a-1,81 (m, 2H).

EXAMPLE 416

({2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)acetic acid

Specified in the header connection receive according to the method of example 379, stages a and b, using methyl ether bromoxynil acid. MS (ESI): mass calculated for C20H N2O3S, 368,12; found m/z 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), 3,64 (c, 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), 0,71-0,65 (m, 2H).

EXAMPLE 417

Ethyl ester of 6-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)hexanoic acid

Specified in the header connection receive according to the method of example 379, step A, using the ethyl ester of 6-Bromhexine acid. MS (ESI): mass calculated for C26H32N2O3S, 452,21; found m/z 453,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, 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), to 2.65 (t, J=7,8, 2H), 2,30 (t, J=7,6, 2H), 1,81-of 1.74 (m, 1H), 1,69-1,60 (m, 2H), 1,59 of 1.50 (m, 2H), 1,37-of 1.27 (m, 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 header connection receive according to the method of example 379, step A, using the ethyl ester of 7-bromoheptanoate acid. MS (ESI): mass calculated for C27H34N2O3S, 466,23; found m/z 467,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), 7,60 (d, 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), 1,67-1,58 (who, 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 is obtained from the compound of example 417, following the method of example 379, step C. MS (ESI): mass calculated for C24H28N2O3S, 424,18; found m/z 425,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,17 (users, 1H), 7,69 (d, J=8,1, 1H), 7,65 (d, 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 is obtained from the compound of example 418, following the method of example 379, step C. MS (ESI): mass calculated for C25H30N2O3S, 438,2; found m/z 439,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 12,57 (users, 1H), 7,72 (d, 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), and 2.26 (t, J=7,6, 2H), 1,97-1,90 (m, 1H), 1,67-of 1.56 (m, 4H), 1,41-of 1.26 (m, 4H), 0,80-to 0.73 (m, 2H), 0,62 is 0.55 (m, 2H).

EXAMPLE 421

N1-{2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}-N1-cyclopropylamino-1,3-diamine

Specified in the header connection receive pursuant to methods of example 378, step A, using cycloprop the Lamin, example 379, step A, using 2-(3-bromopropyl)isoindole-1,3-dione, and example 403. MS (ESI): mass calculated for

With21H25N3OS, 367,17; found m/z 468,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=7,6, 1H), 7,65 (d, 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 (users, 2H), 0,54-of 0.48 (m, 2H), 0,44-to 0.39 (m, 2H).

EXAMPLE 422

N-[3-({2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]ndimethylacetamide

Specified in the title compound is obtained from the compound of example 421, following the method of example 405. MS (ESI): mass calculated for C23H27N3O2S, 409,18; found m/z 410,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, 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 (users, 1H), 3,26 (DD, J=6,1, 5,8, 2H), 2,89-and 2.83 (m, 4H), to 2.75 (t, J=6,8, 2H), 1,89 (c, 3H), 1,84-of 1.78 (m, 1H), a 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 header connection receive according to the method of example 421, using isobutyrate. MS (ESI): mass calculated for C25H31N3O2S, 437,21; found m/z 438,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,37 (t, J=8,1, 1H), 7,30-of 7.23 (m, 5H), 6,54 (users, 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 (d, 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 header connection receive according to the method of example 422, using benzoyl chloride. MS (ESI): mass calculated for C28H29N3O2S, 471,20; found m/z 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 header connection receive according to the method of example 422, using 4-chlorobenzylchloride. MS (ESI): mass calculated for C28H28ClN3O2S, 505,16; found m/z 506,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,80 (t, J=5,0, 1H), 7,68 (d, 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 header connection receive according to the method of example 422, using methanesulfonanilide. MS (ESI): mass calculated for C22H27N3O 3S2, 445,15; found m/z 446,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, 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 (users, 1H), 3.15 in (t, J=6,1, 2H), 2,88 (c, 3H), 2,87-2,82 (m, 4H), 2,78 (t, J=6,1, 2H), 1,82-1,71 (m, 3H), 0,58-of 0.52 (m, 2H), 0,49-0,43 (m, 2H).

EXAMPLE 427

Salt triftormetilfullerenov acid [3-({2-[4-(benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]amide propane-2-sulfonic acid

Specified in the header connection receive according to the method of example 422 using propane-2-sulphonylchloride. MS (ESI): mass calculated for C24H31N3O3S2, 473,18; found m/z 474,4 [M+H]+.

1H NMR (400 MHz, CD3OD): the 7.65 (d, J=7,8, 1H), 7,53 (d, 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 (d, J=4,04, 3H), of 1.23 (d, 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 header connection receive according to the method of example 379, step A, using the ethyl ester of 8-bromooctanoate acid. MS (ESI): mass calculated for C28H36N2O3S, 480,24; found m/z 481,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,63 (d, 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), of 2.64 (t, J=7,3, 2H), 2,28 (t, J=7,1, 2H), 1,8-of 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).

EXAMPLE 429

1-[3-({2-[4-(Benzothiazol-2-yloxy)phenyl]ethyl}cyclopropylamino)propyl]-3-prilocaine

Specified in the header connection receive according to the method of example 422, using phenylisocyanate. MS (ESI): mass calculated for C28H30N4O2S, 486,21; found m/z 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 (users, 1H), 3,16-to 3.09 (m, 2H), 2,70-of 2.64 (m, 4H), to 2.57 (t, J=7,1, 2H), 1,67-to 1.60 (m, 1H), 1,60-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 is obtained from the compound of example 428, following the method of example 379, step C. MS (ESI): mass calculated for C26H32N2O3S, 452,21; found m/z 453,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 12,76 (users, 1H), 7,72 (d, J=7,6, 1H), 7,63 (d, 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

To a solution of N-1-{2-[4-(benzothiazol-2-yloxy)FeNi is]ethyl}-N1-cyclopropylamino-1,3-diamine (example 421, 330 mg, 0.9 mmol) in CH2Cl2(18 ml) is added 2-tetrahydrofuranate 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 is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2)to give white solid (267 mg, yield 64%). MS (ESI): mass calculated for C26H31N3O3S, 465,21; found m/z 466,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), to 7.64 (d, J=8,1, 1H), was 7.36 (t, J=8,1, 1H), 7,32 (users, 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), of 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 header connection receive according to the method of example 431 using glycolic acid. MS (ESI): mass calculated for C23H27N3O3S, 425,18; found m/z 426,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73-7,63 (m, 2H), 7,44 (users, 1H), 7,40-7,33 (m, 1H), 7,29-to 7.18 (m, 5H), 4,21 (c, 1H), 3,91 (c, 2H), 3,37 of 3.28 (m, 2H), 2,90-2,82 (m, 4H), to 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)m is Slana acid

A.{2-[4-(Benzothiazol-2-yloxy)phenoxy]ethyl}cyclopropylamine

To a stirred solution of 2-[4-(2-bromo-ethoxy)phenoxy]benzothiazole (example 9, 1.1 g, 3.14 mmol) in CH3CN (31 ml) add cyclopropylamine (1,09 ml, 15.7 mmol) and N,N-diisopropylethylamine (1.1 ml, 6,28 mmol). The mixture is heated to 60 ºC for 16 h, cooled to room temperature and then dissolved in CH2Cl2(100 ml). The solution is washed with N2About (2×20 ml), dried and concentrated. The resulting oil purified on SiO2(40 g, 0-15% CH3OH/CH2Cl2), getting a clear oil (999 mg, yield 98%). MS (ESI): mass calculated for C18H18N2O2S, 326,11; found m/z 327,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, 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), a 4.03 (t, J=5,3, 2H), 3,06 (t, J=5,3, 2H), 2,20-and 2.14 (m, 1H), 2,02 (user., 1H), 0,47-0,41 (m, 2H), 0.39 to-0,34 (m, 2H).

CenturyEthyl 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 CH3CN (29 ml) is added ethyl ether 4-pamakani acid (625 μl, 4,37 mmol) and N,N-diisopropylethylamine (1.0 ml, of 5.82 mmol). The mixture is heated to 60ºC for 16 h, cooled to room temperature and then dissolved in CH2Cl2(100 ml). The solution is washed with N2About (2×20 ml), dried and concentrated the resulting oil purified on SiO 2(40 g, 0-50% EtOAc/hexane)to give a colorless oil (1.0 g, yield 78%). MS (ESI): mass calculated for C24H28N2O4S, 440,18; found m/z 441,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, 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), of 3.00 (t, J=6,3, 2H), 2,71 (t, J=7,1, 2H), 2,31 (t, J=7,1, 2H), 1,90-1,80 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)phenoxy]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 3:1 THF/CH3OH (80 ml) is added lithium hydroxide (211 mg, 8,8 mmol) in water (20 ml). The resulting solution was stirred at room temperature for 16 h and then adjusted the pH to 7 using 1N. aqueous HCl. The mixture is extracted with CH2Cl2(2×100 ml). The combined organic phase concentrated under reduced pressure. The resulting oil purified on SiO2(40 g, 0-10% CH3OH/CH2Cl2)to give white solid (877 mg, yield 97%). MS (ESI): mass calculated for C22H24N2O4S, 412,15; found m/z 413,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,44 (users, 1H), 7,68 (d, J=8,1, 1H), 7.62mm (d, 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), of 3.56 (t, J=5,005, 2H), 3,32 (t, J=8,1, 2H), 2,67-2,60 (m, 1H), the 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 header connection receive according to the method of example 251, step B, using 1-(3-aminopropyl)pyrrolidin-2-it. MS (ESI): mass calculated for C21H23N3O2S, 381,15; found m/z 382,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, 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 (c, 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 header connection receive according to the method of example 409 using formaldehyde. MS (ESI): mass calculated for C22H25N3O2S, 395,17; found m/z 396,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), to 7.64 (d, J=8,1, 1H), 7,43-7,27 (m, 5H), from 7.24 (t, J=8,1, 1H), 3,54 (c, 2H), 3,32 (DD, J=7,1, 7,1, 4H), 2,43 (t, J=7,1, 2H), 2,34 (t, J=7,1, 2H), 2,23 (c, 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 header connection receive according to the method of example 409 using acetone. MS (ESI): mass calculated for C24H29N3O2S, 423,20; found m/z 424,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, 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 (c, 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), of 1.02 (d, J=6,6, 6H).

EXAMPLE 437

1-(3-{[4-(Benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-he

Specified in the header connection receive according to the method of example 409 using acetaldehyde. MS (ESI): mass calculated for C23H27N3O2S, 409,18; found m/z 410,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,43-7,34 (m, 3H), 7,32-of 7.23 (m, 3H), 3,56 (c, 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 1,91 (m, 2H), 1,73-of 1.64 (m, 2H), was 1.04 (t, J=7,1, 3H).

EXAMPLE 438

[4-(Benzothiazol-2-yloxy)benzyl]cyclopropylamine

Specified in the header connection receive according to the method of example 251, step B, using cyclopropylamine. MS (ESI): mass calculated for C17H16N2OS, 296,10; found m/z 297,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,63 (d, 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 (c, 2H), 2,19-2,12 (m, 1H), 1,86 (users, 1H), 0,48-0,35 (m, 4H).

EXAMPLE 439

N1-[4-(Benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine

Specified in the header connection receive according to the method of example 421, using the compound of example 438. MS (ESI): mass calculated for C20H 23N3OS, 353,16; found m/z 354,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,41-to 7.32 (m, 3H), 7,30-of 7.23 (m, 3H), 3.75 to (c, 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 (users, 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 header connection receive according to the method of example 422, using isobutyrate. MS (ESI): mass calculated for C24H29N3O2S, 423,20; found m/z 424,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,40-7,22 (m, 6H), 6,26 (users, 1H), of 3.73 (c, 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), of 1.09 (d, 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)-3-isopropylamino

Specified in the header connection receive according to the method of example 422 using isopropyltoluene. MS (ESI): mass calculated for C24H30N4O2S, 438,21; found m/z 439,4 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.69 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,38-7,29 (m, 3H), 7,27-7,20 (m, 3H), 5,44 (users, 1H), 5,15 (d, J=7,8, 1H), a 3.87 is 3.76 (m, 1H), 3,70 (c, 2H), 3,12 (DD, J=6,3, 6,1, 2H), has 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-(Benzo is a thiazol-2-yloxy)benzyl]piperidine-4-yl}-3-isopropylamino

Specified in the header connection receive according to the method of example 253, step C, using isopropyltoluene. MS (ESI): mass calculated for C23H28N4O2S, 424,19; found m/z 425,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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 (c, 2H), 2,82 (d, J=11,6, 2H), 2,13 (t, J=10,9, 2H), was 1.94 (d, J=11,9, 2H), 1.69 in (users, 1H), 1,48-of 1.36 (m, 2H), 1.14 in (d, J=6,6, 6H).

EXAMPLE 443

Methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid

Specified in the header connection receive according to the method of example 253, step C, using methyl ether Chlorococcales acid. MS (ESI): mass calculated for C22H23N3O4S, 425,14; found m/z to 426.2 [M+H]+.

1H NMR (400 MHz, CDCl3): for 7.78 (d, 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 (c, 2H), 3,81-and 3.72 (m, 1H), 3,41 (c, 3H), 3,11 (d, J=10,9, 2H), 2,59-2,47 (m, 2H), 2.00 in 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 header connection receive according to the method of example 253, using isobutyrate. MS (ESI): mass calculated for C23H27N3O2S, 409,18; found m/z 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 (d, J=8,6, 2H), 7,41-7,33 (m, 2H), 7,27 (t, J=8,1, 1H), 4,33 (c, 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 (d, J=6,8, 6H).

EXAMPLE 445

{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid

Specified in the title compound is obtained from the compound of example 253, step D, and following the procedure of example 431. MS (ESI): mass calculated for C24H27N3O3S, 437,18; found m/z 438,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 11,03 (users, 1H), 7,73 (d, 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 (d, J=7,8, 1H), or 4.31 (t, J=8.34 per, 1H), 3,98-to 3.89 (m, 1H), 3,84 (c, 2H), 3,19 (d, 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 is obtained from the compound of example 253, step D, and following the method of example 254, step D. MS (ESI): mass calculated for C23H25N3O3S, 423,16; found m/z 424,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,80 (d, 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 (c, 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-hydroxypyrrolidine-2-he

p> Specified in the title compound is obtained from the compound of example 253, step D, and following the method of example 254, step D. MS (ESI): mass calculated for C23H25N3O3S, 423,16; found m/z 424,3 [M+H]+.

1H NMR (400 MHz, CD3OD): 7,80 (d, 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 (c, 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 header connection receive according to the method of example 253, step C, using trimethylsilyltriflate. MS (ESI): mass calculated for

With20H22N4O2S, 382,15; found m/z 383,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=7,8, 1H), 7,63 (d, 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 (d, J=4,6, 1H), 3,84 (c, 1H), 3,56 (users, 1H), 3,49 (c, 2H), 2,81 (d, J=11,6, 2H), 2,12 (t, J=11,1, 2H), 1,90 (d, 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 is obtained from the compound of example 443, following the method of example 433, step C. MS (ESI): mass calculated for C21H21N3O4S, 411,13; found m/z 412,3 [M+H]+.

1H NMR (400 MHz, CD3OD): for 7.78 (d, J=8,1, 1H), to 7.64 (d, J=8,1, 1H), 7,55 is 7.50 (m, 2H), 7,4 and 7.36 (m, 3H), 7,31 (t, J=8,1, 1H), 3,84 (c, 2H), 3,81-and 3.72 (m, 1H), 3,11 (d, 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 header connection receive according to the method of example 431 using glycolic acid. MS (ESI): mass calculated for C21H23N3O3S, 397,15; found m/z 398,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=7,8, 1H), 7,65 (d, J=8,1, 1H), 7,40-7,35 (m, 3H), 7,31-of 7.23 (m, 3H), 6,83 (d, J=8,1, 1H), 5,33, (users, 1H), 3,99 (c, 2H), a 3.87 of 3.75 (m, 1H), 3,50 (c, 2H), 2,85 (d, J=11,4, 2H), and 2.14 (t, J=10,9, 2H), 1,92 (d, 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 header connection receive according to the method of example 431 using triperoxonane acid. MS (ESI): mass calculated for C21H20F3N3O2S, 435,12; found m/z 436,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,3, 2H), 7,54 (d, J=8,6, 2H), 7,47 (d, J=8,8, 2H), 7,41 (t, J=8,3, 1H), 7,34-7,28 (m, 1H), 4,24 (c, 2H), 4,15-was 4.02 (m, 1H)and 3.59 (d, J=12,1, 2H), 3,40, (users, 1H), 2,87 (t, J=11,9, 2H), 2,22-2,02 (m, 4H).

EXAMPLE 452

2-[4-(1,1-Diocletianopolis-4-ylmethyl)phenoxy]benzothiazole

Specified in the header connection receive according to the method of example 251, using thiomorpholine-1,1-dioxide. MS (ESI): m the SSA, calculated for C18H18N2O3S2, 374,08; found m/z 375,2 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, 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 (c, 2H), 3,03 (d, J=26,3, 8H).

EXAMPLE 453

tert-Butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl}carbamino acid

Specified in the header connection receive according to the method of example 253, using N-(sulphonylchloride)tert-butyl ether carbamino acid. MS (ESI): mass calculated for C24H30N4O5S2, 538,17; found m/z 519,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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 (users, 1H), 3,55 (c, 2H), 3,39-3,29 (m, 1H), and 2.83 (d, J=11,7, 2H), 2,31-to 2.18 (m, 2H), 1,98 (d, J=11,7, 2H), 1,72-1,59 (m, 2H), 1,47 (c, 9H).

EXAMPLE 454

N-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide

Specified in the header connection receive according to the method of example 253, step C, using acetylchloride. MS (ESI): mass calculated for C21H23N3O2S, 381,15; found m/z 382,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, 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 (users, 1H), a 3.87 is 3.76 (m, 1H), 3,54 (c, 2H), 2,86 (d, J=12,1, 2H), 2,17 (t, J=11,4, 2H), 1,97 (c, 3H), of 1.93 (d, J=11,9, 2H), 1.56 to the 1.44 (m, 2H).

EXAMPLE 455

N-{1-[4-(Benzo is a thiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfone

Specified in the header connection receive according to the method of example 253, step C, using N,N-dimethylsulphamoyl. MS (ESI): mass calculated for

With21H26N4O3S2, 446,14; found m/z 447,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,41-7,35 (m, 3H), 7,32-of 7.23 (m, 3H), 4,37 (d, J=7,8, 1H), 3,49 (c, 2H), 3,28-3,17 (m, 1H), 2,81 (d, J=10,9, 2H), 2,78 (c, 6H), 2,11 (t, J=11,1, 2H), 1,98 (d, 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 header connection receive according to the method of example 253, step C, using utilitzant. MS (ESI): mass calculated for C22H26N4O2S, 410,18; found m/z 411,5 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,42-7,34 (m, 3H), 7,32-of 7.23 (m, 3H), 4,54 (users, 1H), 4,45 (d, J=7,6, 1H), 3,67-3,55 (m, 1H), 3,50 (c, 2H), 3,23-3,14 (m, 2H), 2,80 (d, J=11,9, 2H), 2.13 in (t, J=11,4, 2H), 1,93 (d, J=12,6, 2H), 1,48-of 1.36 (m, 2H), 1,12 (t, J=7,3, 3H).

EXAMPLE 457

1-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene

Specified in the header connection receive according to the method of example 253, step C, using ethylisothiocyanate. MS (ESI): mass calculated for C22H26N4OS2, 426,15; found m/z 427,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, 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 (users, 1H), 5,74 (users, 1H), 4,20-4,00 (m, 1H), 3,51 (c, 2H), 3,47-to 3.35 (m, 2H), 2,82 (d, J=11,6, 2H), 2.05 is (t, J=11,1, 2H), 2,05 (d, 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 header connection receive according to the method of example 253, step C, using 1-propanesulfonate. MS (ESI): mass calculated for C22H27N3O3S2, 445,15; found m/z KZT 446.4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,40-7,34 (m, 3H), 7,32-7,22 (m, 3H), around 4.85 (d, J=8,1, 1H), 3,48 (c, 2H), 3,36-3,24 (m, 1H), 3,02-to 2.94 (m, 2H), 2,81 (d, J=11,9, 2H), 2,11 (t, J=10,6, 2H), 1,95 (d, J=12,6, 2H), 1,89-of 1.78 (m, 2H), 1,65-and 1.54 (m, 2H), was 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 header connection receive according to the method of example 253, step C, using 2-propanesulfonate. MS (ESI): mass calculated for C22H27N3O3S2, 445,15; found m/z KZT 446.4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,41-7,35 (m, 3H), 7,32-7,24 (m, 3H), 3,79 (d, J=5,6, 1H), 3,51 (c, 2H), 3,38-of 3.27 (m, 1H), 2,89-2,78 (m, 2H), 2,19-of 1.94 (m, 5H), to 1.76 (d, J=30,8, 6H), 1,69-of 1.55 (m, 2H).

EXAMPLE 460

N-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide

p> Specified in the title compound is obtained from the compound of example 453, following the procedure of example 253, step C. MS (ESI): mass calculated for C19H22N4O3S2, 418,11; found m/z 419,4 [M+H]+.

1H NMR (400 MHz, CDCl3): is 10.68 (users, 1H), 7,60 (d, J=8,3, 1H), 7,56 (d, 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 (users, 2H), 4,10 (c, 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 header connection receive according to the method of example 431, formic acid. MS (ESI): mass calculated for C20H21N3O2S, 367,14; found m/z 368,4 [M+H]+.

1H NMR (400 MHz, CDCl3): to 12.28 (users, 1H), 7,73 (d, J=7,8, 1H), 7,68 (d, J=7,8, 1H), 7,47-7,24 (m, 6H), 6,33 (d, J=7,3, 1H), 4,05-of 3.94 (m, 1H), 3,80 (c, 2H), 3,14 (d, J=11,6, 2H), 2,41 (t, J=11,9, 2H), 1,99 (d, 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 header connection receive according to the method of example 253, step C, using ethylchloride. MS (ESI): mass calculated for C22H25N3O3S, 411,16; found m/z 412,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, J=8,1, 1H), 7,41-7,34 (m, 3H), 7,32-7,22 (m, 3H), 4,62 (users, 1H), 4,10 (DD, J=7,3, 6,8, 2H), 3,59-3,51 (m, 1H), 3,49 (c 2H), 2,80 (d, J=11,6, 2H), 2,12 (t, J=11,6, 2H), 1,93 (d, 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 header connection receive according to the method of example 253, step C, using propionate. MS (ESI): mass calculated for C22H25N3O2S, 395,17; found m/z 396,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,41-7,34 (m, 3H), 7,32-7,22 (m, 3H), 5,61 (d, J=8,1, 1H), a 3.87 is 3.76 (m, 1H), 3,49 (c, 2H), 2,82 (d, J=11,9, 2H), 2,22-2,07 (m, 4H), 1,90 (d, 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 header connection receive according to the method of example 253, step C, using butyrylcholine. MS (ESI): mass calculated for C23H27N3O2S, 409,18; found m/z 410,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,40-7,35 (m, 3H), 7,31-of 7.23 (m, 3H), 5,64 (d, J=8,1, 1H), a 3.87-of 3.77 (m, 1H), 3,49 (c, 2H), 2,81 (d, J=11,6, 2H), 2,16-2,07 (m, 4H), at 1.91 (d, J=12,9, 2H), 1,71 is 1.60 (m, 2H), 1,51-of 1.39 (m, 2H), of 0.93 (t, J=7,3, 3H).

EXAMPLE 465

1-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-proprotein

Specified in the header connection receive according to the method of example 253, step C, using propositional. MS (ESI): mass calculated on the I 23H28N4O2S, 424,19; found m/z 425,5 [M+H]+.

1H NMR (400 MHz, CDCl3): of 7.70 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,39-7,33 (m, 3H), 7,28-7,21 (m, 3H), 5,54 (users, 1H), lower than the 5.37 (d, J=8,1, 1H), 3,66 of 3.56 (m, 1H), 3,48 (c, 2H), 3,11 (DD, J=7,1, 6,8, 2H), 2,80 (d, J=11,1, 2H), 2,11 (t, J=11,1, 2H), 1.91 a (d, 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 header connection receive according to the method of example 253, step C, using propellorhead. MS (ESI): mass calculated for C23H27N3O3S, 425,18; found m/z 426,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,63 (d, 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 (c, 2H), and 2.79 (d, J=11,6, 2H), 2,10 (t, J=10,9, 2H), at 1.91 (d, J=11,1, 2H), 1,67-of 1.56 (m, 2H), 1,52-of 1.40 (m, 2H), to 0.92 (t, J=7,6, 3H).

EXAMPLE 467

1-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metalmachine

Specified in the header connection receive according to the method of example 253, step C, using methyl isocyanate. MS (ESI): mass calculated for C21H24N4O2S, 396,16; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,45-7,34 (m, 3H), 7,33-7,22 (m, 3H), 5,71 (users, 2H), 3,69-3,59 (m, 1H), 3,56 (c, 2H), 2,87 (d, J=11,9, 2H), 2,73 (d, J=4,8, 3H), of 2.21 (t, J=10,1, 2H), 1.93 and (d, J=10,4, 2H), 1,58-of 1.45 (m, 2H).

P the EMER 469

1-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloxetane

Specified in the header connection receive according to the method of example 255, step C, using methyl isocyanate. MS (ESI): mass calculated for C22H26N4O2S, 410,18; found m/z 411,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, 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 (c, 2H), 2,93 (d, J=11,9, 2H), and 2.79 (d, J=4,8, 3H), 2,71 (c, 3H), of 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 header connection receive according to the method of example 255, step C, using trimethylsilyltriflate. MS (ESI): mass calculated for

With21H24N4O2S, 396,16; found m/z 397,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, J=8,1, 1H), 7,42-7,34 (m, 3H), 7,32-7,21 (m, 3H), 4,93 (c, 2H), 4,16-a 4.03 (m, 1H), 3,50 (c, 2H), 2,94 (d, J=11,4, 2H), was 2.76 (c, 3H), of 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 header connection receive according to the method of example 255, step C, using acetylchloride. MS (ESI): mass calculated for C22H25N3O2S, 395,17; found m/z 396,4 [M+H]+ .

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,65 (d, 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 (c, 2H), 3,01-2,90 (m, 2H), 2,84 (c, 3H), 2,15-of 2.09 (m, 2H), 2,07 (c, 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 header connection receive according to the method of example 255, step C, using methylchloroform. MS (ESI): mass calculated for C21H25N3O3S, 411,16; found m/z 412,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, 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 (c, 3H), 3,51 (c, 2H), 2,95 (d, J=11,4, 2H), 2,78 (c, 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)benzyl]piperidine-4-yl}-N-methoxylamine acid

Specified in the header connection receive according to the method of example 255, step C, using methyl ether Chlorococcales acid. MS (ESI): mass calculated for C23H25N3O4S, 439,16; found m/z 440,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,73 (d, J=8,1, 1H), 7,66 (d, 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 (c, 3H), 3,51 (c, 2H), 2,97 (d, J=11,9, 2H), 2,88 (c, 3H), 2,13 (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-and the}-N-methylocella acid

Specified in the title compound is obtained from the compound of example 473, following the method of example 433, step C. MS (ESI): mass calculated for C22H23N3O4S, 425,14; found m/z 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 (c, 2H), 2,93 (d, J=11,897, 2H), 2,75 (c, 3H), 2,01 (t, J=11,9, 2H), 1,82-of 1.65 (m, 2H), 1,58-1,47 (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 CH3OH (2.0 ml) is added sodium acetate (180 mg, 2.2 mmol) at room temperature. The suspension becomes a clear solution. The solution is cooled to 0ºC. Added dropwise ciambrone (159 mg, 1.5 mmol) in CH3OH (0.7 ml). The reaction mixture was stirred at 5ºC for 2 h and then overnight at ambient temperature. The mixture is filtered through a Frit (with a porous glass filter, the filtrate adsorb on silica gel (40 g) and purified (0-10% CH3OH/CH2Cl2), getting unstable oil (123 mg, yield 34%). MS (ESI): mass calculated for C20H20N4OS, 364,14; found m/z 365,3 [M+H]+.

B.N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine

is the solution of 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ellenabad (123 mg, 0.34 mmol) in DMF (2 ml) is added hydroxylamine hydrochloride (41,5 mg to 0.60 mmol) followed by addition of small portions of sodium carbonate (119 mg, 1.12 mmol). The reaction mixture was stirred at room temperature for 2 h and partitioned between EtOAc (20 ml) and H2O (20 ml). The organic phase is washed with saturated salt solution, dried and concentrated under reduced pressure, obtaining the crude product as a pale solid. The crude product is purified on SiO2(12 g, 0-10% CH3OH/CH2Cl2)to give white solid (117 mg, yield 86%). MS (ESI): mass calculated for C20H23N5O4S, 397,16; found m/z 398,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,38-to 7.32 (m, 3H), 7,28-7,21 (m, 3H), 4,69 (users, 2H), 3.46 in (c, 2H), 3.27 to and 3.16 (m, 1H), 2,78 (d, J=10,9, 2H), 2,04 (t, J=11,1, 2H), 1,92 (d, J=11,1, 2H), 1,51-to 1.38 (m, 2H).

EXAMPLE 476

Isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid

Specified in the header connection receive according to the method of example 253, step C, using isopropyltoluene. MS (ESI): mass calculated for C23H27N3O3S, 425,18; found m/z 426,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,63 (d, J=8,1, 1H), 7,38-7,33 (m, 3H), 7,31-7,21 (m, 3H), 4.95 points-is 4.85 (m, 1H), and 4.75 (d, J=7,1, 1H), to 3.58-3.49 points (m, 1H), 3,47 (c, 2H), and 2.79 (d, J=11,6, 2H),2,09 (t, J=11,4, 2H), 1.91 a (d, J=11,9, 2H), 1,50-of 1.39 (m, 2H), 1,21 (d, J=6,5, 6H).

EXAMPLE 477

3-{1-[4-(Benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloxetane

Specified in the header connection receive according to the method of example 253, step C, using N,N-dimethylcarbamoyl. MS (ESI): mass calculated for

With22H26N4O2S, 410,18; found m/z 411,4 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,71 (d, 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 (c, 2H), 2,87 (c, 6H), of 2.81 (d, J=11,6, 2H), 2,11 (t, J=11,9, 2H), 1.93 and (d, 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 header connection receive according to the method of example 253, step C, using chlorocarbonylsulfenyl ester of acetic acid. MS (ESI): mass calculated for C23H25N3O4S, 439,16; found m/z 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, (c, 2H), 3,93-3,82 (m, 1H), 3,50 (c, 2H), and 2.83 (d, J=11,9, 2H), 2,15 (c, 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

Indicated the data in the header connection receive according to the method of example 253, stage With using benzoylation. MS (ESI): mass calculated for C27H26N4O2S2, 502,15; found m/z 503,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 10,80 (d, J=8,1, 1H), 9,06 (c, 1H), 7,81 (d, J=8,3, 2H), 7,72 (d, J=8,3, 1H), 7,65 (d, 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 (c, 2H), 2,80 (d, J=11,1, 2H), and 2.26 (t, J=10,1, 2H), 2,12 (d, J=11,9, 2H), 1,76-of 1.64 (m, 2H).

B.{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) is added 10% aqueous sodium hydroxide (10 ml). The reaction mixture is heated at the boiling point under reflux for 1 h Obtained white suspension is cooled to room temperature and extracted with a mixture of 10% CH3OH/CH2Cl2(3×50 ml). The organic layer is dried (Na2SO4) and concentrated under reduced pressure, obtaining the crude product in the form of not-quite-white solid. The crude product is purified on SiO2(40 g; 0-10% CH3OH/CH2Cl2), getting mentioned in the title compound as a white solid (219 mg, yield 92%). MS (ESI): mass calculated for C20H22N4OS2, 398,12; found m/z 399,3 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,72 (d, J=8,1, 1H), 7,68 (d, 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), 3,57 (c, 2H), 2,88 (d, J=11,1, 2H), 2,29 (c, 2H), 2,20 (who, J=11,1, 2H), 2,04 (d, J=10,1, 2H), 1.60-to a 1.45 (m, 2H).

EXAMPLE 480

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

Specified in the header connection receive according to the method of example 37, using piperidine-4-ylmethanol. MS (ESI): mass calculated for C21H25N3O3, 367,19; found m/z 368,4 [M+H]+.

1H NMR (400 MHz, DMSO-d6): 12,24 (c, 1H), 7,32 (c, 2H), 7,27 (d, J=8,9, 2H), 7,08 (c, 2H), 7,00 (d, J=8,9, 2H), to 4.41 (c, 1H), 4.09 to (c, 2H), 3,24 (c, 2H), 2,92 (d, J=11,1, 2H), 2,68 (c, 2H), 1,98 (t, J=11,6, 2H), 1,62 (d, J=11,6, 2H), 1,24 (users, 1H), 1,11 (d, J=9,2, 2H).

EXAMPLE 481

2-[4-(2-Morpholine-4-ylethoxy)phenoxy]benzoxazol

Specified in the header connection receive according to the method of example 11, using 4-(2-chloroethyl)morpholine. MS (ESI): mass calculated for C19H20N2O4, 340,14; found m/z 341,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=7,1, 1H), 7,42 (d, 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 header connection receive according to the method of example 12 using 4-(2-chloroethyl)morpholine and 2-chlorobenzothiazole. MS (ESI): mass calculated for C19H20N2O3S, 356,24; found m/z 341,1 [M+H]+.

1H NMR (400MHz, CDCl3): 7,74 (d, J=7,6, 1H), 7,66 (d, 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 header connection receive according to the method of example 12 using 4-(2-chloroethyl)piperidine and 2-chlorobenzothiazole. MS (ESI): mass calculated for C20H22N2O2S, 354,14; found m/z 355,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,74 (d, J=8,1, 1H), 7,65 (d, 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), of 2.81 (t, J=6,0, 2H), 2,58-2,48 (users, 4H), 1,68 is 1.58 (m, 4H), 1,52-of 1.42 (m, 2H,).

EXAMPLE 484

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

Specified in the header connection receive according to the method of example 11, using (2-chloroethyl)diethylamine. MS (ESI): mass calculated for C19H22N2O3, 326,16; found m/z 327,1 [M+H]+.

1H NMR (400 MHz, CDCl3): 7,51 (d, J=7,6, 1H), 7,42 (d, 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 results presented in the present description, illustrate the results of tests carried out for the compounds according to this invention.

The trial of recombinant human hydrolases LTA4 in the test activity inhibitor guy who rolety LTA4

The compounds of this invention were tested for activity inhibitor hydrolases LTA4 against recombinant human hydrolases LTA4 (rhLTA4H). Vectors for the expression of rhLTA4H received and used essentially in the following manner: DNA encoding hydrolase LTA4, amplified polymerase chain reaction (PCR)using a library of human placental cDNA as template. Oligonucleotide primers for PCR reactions were based on the 5'-end and the complement of the 3'end of the published nucleotide sequence for the coding region of the gene of human hydrolases LTA4 (C.D. Funk et al., Proc. Natl. Acad. Sci. USA 1987, 84:6677-6681). Amplificatory DNA fragment of 1.9 TPN encoding hydrolase LTA4, was isolated and cloned into the pFastBac1 vector (Invitrogen). Recombinant baculovirus generated, as described by the manufacturer, and used to infect cells Spodoptera frugiperda (Sf-9). The enzyme, a recombinant hydrolase LTA4, was purified from infected cells, Sf-9, mainly, as described J.K. Gierse et al. (Protein Expression and Purification 1993, 4:358-366). The solution of purified enzyme was adjusted so that it contained 0,29 mg/ml hydrolases LTA4, 50 mm Tris (pH 8.0), 150 mm NaCl, 5 mm dithiotreitol, 50%glycerol, and not containing EDTA full cocktail protease inhibitors (Roche). The specific activity of the enzyme was about 3.8 ámol/min/mg.

The substrate LTA4 come and complex LTA4 methyl ester (Cayman Chemical) processing 67 equivalents of NaOH under nitrogen atmosphere at room temperature for 40 minutes The substrate LTA4 in the form of the free acid was kept frozen at-80ºC until requested. Each compound was diluted to different concentrations in the buffer for analysis (0,1M potassium phosphate (pH 7,4), 5 mg/ml BSA, not containing fatty acids), containing 10% DMSO. 25-µl aliquot of the dilution of each compound were incubated for 10 min at room temperature with an equal volume of buffer for analysis, containing 36 ng of recombinant human LTA4H. Then the solution is brought up to a volume of 200 μl of buffer for analysis. LTA4 (in the form of the free acid) was thawed and diluted in buffer for analysis of concentrations up to 357 ng/ml, and 25 μl (9 ng) substrate LTA4 was added to the reaction mixture (total volume=225 μl) at time zero (the start of the reaction). Each reaction was carried out at room temperature for 10 minutes the Reaction was stopped by dilution of 10 μl of the reaction mixture of 200 μl of buffer for analysis. LTB4 was quantified in the diluted sample using a commercially available method enzyme immunoassay (Cayman Chemical Co.) according to the manufacturer's recommendations. In each experiment, as expected, performed positive controls in essentially identical conditions but without addition of the compound inhibitor and negative control containing all components analysis, in addition to the enzyme. The values of the IC50determined (empirically), the chasing data activity at various concentrations of the compounds to a four-parameter equation, using the program Grafit (Erithacus software).

Presented in the tables below the value of the IC50as expected, within a typical three-time variability tests of this type. The values presented are, in General, the average of (1-3) definitions.

Table 1
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1164515941
132461713592
14959513625
27777 2712
361478348155
44892148419

Table 2
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
121001761229815
1522180230260
18618318325 12
227192332822
2311955833113
2542024334100
3117206433624
8023207163537
815211935745
10232141835811
10414 2241435948
109212252536033
11040250263618
14364251163634
14643255136639
14733259143806
1501261333892
15382624419 4
1559263543721
15672651124468
15712701644728
1611274294507
1639285764544
167372872846227
16827288447119
16932 296334797
17227294648345

Table 3
ExampleIC50(nm)ExampleIC50(nm)
3710134110
123423036
1272923118
13213948539
133111

Stimulated calcium-ionophores the production of LTB4 in mouse blood in the test activity of LTA4H inhibitor

Of mice CD-1 was slaughtered and the blood was collected a heart condition the second puncture in Eparistera syringes. The blood was diluted at a ratio of 1:15 medium RPMI-1640 and 200-µl aliquots of the diluted blood was added to the wells of 96-well titration tablets. Compound-LTA4H inhibitors were obtained at various concentrations in the medium RPMI-1640 containing 1% DMSO and 20 μl of each test solution was added to the well containing the diluted whole blood (final concentration of DMSO of 0.1%). After incubation the contents tiralongo tablet for 15 min at 37 degrees C in a humid chamber in each well of sample was added to the calcium-ionophor A23187 (Sigma Chemical Co., St. Louis, Mo.) (final concentration=20 ng/ml). Incubation continued at the same conditions for a further 10 minutes, giving the opportunity to form LTB4. The reaction was stopped by centrifugation (833×g, 10 min at 4ºC) and supernatant analyzed for LTB4 using a commercially available method enzyme immunoassay (Cayman Chemical Co.) in accordance with the manufacturer's instructions. In each experiment, as expected, performed positive controls in essentially identical conditions but without addition of the compound inhibitor and negative restimulate controls containing all of the component analysis, in addition to the calcium-ionophore. The values of the IC50was determined by fitting the data activity at various concentrations of the compounds to a four-parameter equation using programs the Grafit (Erithacus software).

Table 4
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1144271439472
13414423481264
1489462948411

49
Table 5
ExampleIC50(nm)ExampleIC50(nm)ExampleIC50(nm)
1525125099328143
181621983933185
2212320643334453
239320781336153
8141251159359446
1025525949360246
1045202618138017
109189263437105
15052274331446131
15512728857447240
1562000296133462144
16110029869483161
18015302212

Table 6
ExampleIC50(nm)ExampleIC50(nm)
12736 133290
132347134436

The model induced by arachidonic acid inflammation in mice

Connection-LTA4H inhibitors according to this invention was dissolved in 20% cyclodextrin/H2About at a concentration of 3 mg/ml Solutions were administered with oral probe mice-females line Balb/c mice weighing approximately 20 grams each (0.2 ml per mouse, 30 mg of the compound-of LTA4H inhibitor per kg). Sixty minutes after administration of the inhibitor LTA4H each mouse received topical application of 20 μl of arachidonic acid (100 mg/ml in acetone) in the left ear and only 20 µl of acetone in the right ear. After 3 h, mice were killed, took blood, filled in heparinised syringes and selected 8-mm samples of ear tissue for a biopsy. Ear biopsies were weighed to determine the amount of swelling, then froze to-80º C and kept at this temperature until the determination of the influx of neutrophils.

100-ál aliquots of heparinized blood was added to the wells tiralongo tablet, along with an equal volume of RPMI-1640 medium, and in each well of sample was added to the calcium-ionophor A (final concentration=20 ng/µl). Content tetrazinni the plates were incubated for 10 minutes n and 37 degrees C in a humid chamber. The reaction was stopped by centrifugation (833×g, 10 min at 4ºC). Supernatant analyzed for LTB4 commercially available enzyme-linked immunosorbent assay (Cayman Chemical Co.) in accordance with the manufacturer's instructions. The percentage inhibition of ex vivo stimulated LTB4 production (% Ing. LTB4) was determined by comparison with similarly treated animals except that they were injected with oral probe solution not containing compound inhibitor.

The influx of neutrophils was quantified by measuring the myeloperoxidase activity (MPO), neutrophil-specific enzyme. Ear biopsies homogenized in 0.5 ml of buffer for extraction (0.3m sucrose, 0,22% (wt./about.) bromide of hexadecyltrimethylammonium (CTAB), and 2.5 mm citrate, obtained from 0,5M initial solution of citrate (pH 5.0)). Debris was removed by centrifugation at 14000×g for 10 min 10 µl aliquots of the resulting supernatant were added to the wells tiralongo tablet along with 90 μl of the aliquot dilution buffer (10 mm citrate, 0,22% CTAB) and then adding to each well for sample 20 ál of TMB liquid substrate system (Sigma Chemical Co.). Content tiralongo tablet kept at room temperature for 1 h the Reaction was stopped by adding to each well 100 μl of 1M H2SO4and was determined for each sample activity beloperone the basics on the basis of the absorption at 405 nm. For each animal, the background value for the right eye, treated only with acetone, subtracted from the value for the left eye treated with arachidonic acid in acetone. The percentage inhibition of the influx of neutrophils (% Ing. MPO) compounds according to this invention were determined by comparison with similarly treated animals except that the input oral probe solution did not contain inhibitory connections.

Table 7
Example% Ing. LTB4% Ing. MPO
118395
148156
275072

Table 8
Example% Ing. LTB4% Ing. MPOExample% Ing. LTB4% Ing. MPO
1532292517966
1878832599574
227979263019
2367842749387
8178833257667
1095144336670
15081913608788
1559693 3618690
18087874466443
25080944479048
20667764719089
2508094

Despite the above detailed description and illustration of specific variants of its implementation to the experts in this field will be obvious that the main components of the principles of the invention can be made various changes, application, modification, and expansion (dilatation) without departing from the essence and scope of this invention. It must be borne in mind that the foregoing description is only illustrative and the present invention should not be limited to the specific form or arrangement is in the parts, described and presented in this description.

1. The compound of formula (II):

or its enantiomer, racemate or pharmaceutically acceptable salt, where
X is selected from the group consisting of O and S;
Y is selected from the group consisting of CH2and;
R4represents H;
R6represents H or F; and
R2'defined as R2, a R3'defined as R3as follows:
R2and R3each independently selected from the group consisting of
A) H, C1-7of alkyl, C3-7cycloalkyl, where each of the substituents And independently substituted by 0 or 1 RQand each of these RQDeputy at carbon, which at least one carbon atom removed from the nitrogen;
alternative R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is specified nitrogen accession, and this heterocyclic ring selected from the group consisting of
i) (4-7)-membered heterocyclic ring HetRbwhere specified (4-7)-membered heterocyclic ring HetRbhas one heteroatom, which is specified by the nitrogen attached, and substituted by 0, 1, or 2 substituents at the same or different substituted the atoms, these substituents selected from the group consisting of-RY, -C(O)RY- 0-4alkyls2RY,
-C0-4alkyls(O)NRYRZ- 0-4NRYC(O)RZ- 0-4NRYC(O)CH2ORY,
-C0-4NRYCO2RY, -C0-4NRYC(O)NRYRZ, -C0-4NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4NRWSO2RYtetrazol-5-Il,
-C0-4the N(RY)(SO2)NRYRY,
-C0-4the N(RY)(SO2)NRYCO2RY,

ii) (5-7)-membered heterocyclic ring HetRcwhere specified (5-7)-membered heterocyclic ring has one additional heteroatom, remote from the specified nitrogen attaching at least one carbon atom, with specified additional heteroatom selected from the group consisting of O, S(=O)0-2and >NRMand where specified (5-7)-membered heterocyclic ring HetRcis 0 or 1 carbonyl group;
iv) one of the
2,8-diazaspiro[4.5]Decan-1-one-8-Il,
4-{[(2-tert-butoxycarbonylmethylene)amino]methyl}-
piperidine-1-yl, 4-{[(2-aminocyclohexanol)amino]methyl}piperidine-1-yl, tert-butyl methyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid-9-yl; DG is
RKselected from the group consisting of H, -C1-4of alkyl, each optionally substituted by 1 substituent RN;
RMselected from the group consisting of-SO2RY, -C(O)RY-C(O)1-4ORYeach optionally substituted by 1 substituent RN;
RNselected from the group consisting of HE, NH2, CF3;
RQselected from the group consisting of
-C0-4RAr'- 0-4alkyls2RY, -C0-4NRYRZ,
-C0-4NRYCORY, -C0-4NRYCONRYRZ;
RWselected from the group consisting of RYand-C3-7cycloalkyl;
RYselected from the group consisting of H, -C1-4of alkyl, -C0-4RArand-C0-4RAr'each optionally substituted by 1 substituent RN;
RZselected from the group consisting of RY- 1-2alkyls2RY;
RAris a piece that is attached via a carbon atom, and the specified fragment selected from phenyl, pyridyl;
RAr'represents a 5 to 6-membered cyclic ring having 1 or 2 heteroatoms selected from the group consisting of O, N and >NRYwith 0 unsaturated bonds, having 0 or 1 carbonyl group, where each atom, when valence allows, in each of these cyclic who Alec independently substituted by 0 or 1 R K;
provided that
(a) the R2'and R3'in addition, meet the following conditions:
(e1): the R2'and R3'both are not H when Y is Oh and X represents S;
(E3): the R2'and R3'taken together with the nitrogen to which they are bound, do not form pieperazinove group, when X is O and Y is one of O and CH2;
(E4): the R2'and R3'taken together with the nitrogen to which they are bound, do not form piperidino group, which monogamist saturated 6-membered cyclic group, when X is O and Y is one of O and CH2;
(E5): the R2'and R3'taken together with the nitrogen to which they are bound, do not form any substituted piperidino group or substituted piperazino group where the specified substituted piperidino group or specified substituted pieperazinove group substituted in position 4 by the Deputy XG, with the specified XG has the structure

where n=0, 1, and when ne=1, then XL is a1-6alkyl, OSG represents O or S, and XR1and XR2taken together with the nitrogen to which they are attached, form one of piperidino group, piperazino group, morpholino group, thiomorpholine group and pyrrolidino group, or each of the th of the XR 1and XR2taken independently represent one of H, C1-6of alkyl, aryl, aralkyl,3-8cycloalkyl,3-8cycloalkyl-C1-6of alkyl, heteroalkyl, heteroaryl-C1-6of alkyl, geterotsiklicheskie and heteroseksualci-C1-6of alkyl, where the aryl, aralkyl, cycloalkyl, heteroaryl or heteroseksualci may be optionally substituted by one or more substituents, independently selected from halogen, hydroxy, C1-6of alkyl, C1-6alkoxy, kalogeropoulos1-6of alkyl, kalogeropoulos1-6alkoxy, nitro, cyano,amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or geterotsiklicheskie; and
(b) further provided that when X represents S and Y represents Oh, then one of R2'and R3'is not XCG, while the other represents C1-6alkyl, where XCG is a group

where NS represents one of H, C1-6of alkyl, Halogens1-6of alkyl, allyl and
With1-6alkoxymethyl, and GO is a group associated with the carbon atom, which has a Deputy =O, forming aminogroup with nitrogen, which is linked to a specified GO group.

2. The compound according to claim 1, where the specified R2and R3each independently selected from the group A).

3. The compound according to claim 1, where the specified R2 and R 3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group consisting of i) and ii).

4. The compound according to claim 1, where the specified R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group i).

5. The compound according to claim 1, where the specified R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group ii).

6. The compound according to claim 1, where the specified connection is one of:
2-(4-piperidine-1-ylmethylene)benzoxazole and 2-(2-fluoro-4-piperidine-1-ylmethylene)benzoxazole.

7. The compound according to claim 1, where the specified connection is one of:
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-it;
2-(2-fluoro-4-Piperi the Jn-1 ylmethylene)benzothiazole;
1-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-it;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide;
2-{4-[4-(1H-tetrazol-5-yl)piperidine-1-ylmethyl]phenoxy}benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-it;
4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one;
2-(4-piperidine-1-ylmethylene)benzothiazole;
1-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanesulfonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-trifurcated;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
2-[4-(4-methanesulfonylaminoethyl-1-ylmethyl)phenoxy]benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline;
2-(4-(morpholine-4-yl is ethylenoxy)benzothiazole;
phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide;
ethyl ester of 3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
1-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-it;
[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine;
N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}-propyl)isobutyramide;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}-propyl)-3-Isopropylamine;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-Isopropylamine;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroc pirrolidone-2-it;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-trifurcated;
2-[4-(1,1-diocletianopolis-4-ylmethyl)phenoxy]benzothiazole;
tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-utilmately;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide;
ethyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-propylacetic;
propyl ether {1-[4-(benzodi the evils-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metallocene;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloctane;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metallocene;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine;
isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloctane;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ester of acetic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea;
1'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipiperidine;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-(tetrahydrofuran-2-yl)methanone;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine;
2-(4-Pipera the Jn-1 ylmethylene)benzothiazole;
amide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
2-[4-(4-benzolsulfonate-1-ylmethyl)phenoxy]benzothiazole;
C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
2-(2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-oxoethyl)Cyclopentanone;
ethyl ester {4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
4-(benzothiazol-2-yloxy)benzyl ester 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyric acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)pyrrolidin-2-it;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)carbamino acid;
(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)amide tetrahydrofuran-2-carboxylic acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-4-hydroxypyrrolidine-2-it;
tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl) - carbamino acid;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide econsultancy acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrole-2,5-dione;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}METI the amine;
1-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-carboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methylamine;
benzothiazol-2-yl{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amine;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)carbamino acid;
4-({[4-(benzothiazol-2-yloxy)benzyl]methylamino}methyl)phenol;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-methylpropane-1,3-diamine;
(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propellerblades)methyl ester acetic acid;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-2-hydroxyacetamido;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)methanesulfonamide;
6-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
6-methoxy-2-(4-piperidine-1-ylmethylene)benzothiazole;
dimethylamide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-sulfonic acid;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-pyrrolidin-1 ratanana;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-morpholine-4-ratanana;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}thiophene-2-ylmethanone;
4-methyl-2-(4-piperidine-1-ylmethylene)benzothiazole;
4-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
2-[4-(4,4-deformability-1-ylmethyl)phenoxy]benzothiazole;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanol key is lots;
[4-(benzothiazol-2-yloxy)benzyl]methyl(1-methylpiperidin-4-yl)amine;
3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propionitrile;
4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-it;
2-[4-(3-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamoyl)methyl ester acetic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxy-N-methylacetamide and ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid.

8. Method for the treatment or prevention of LTA4H-mediated condition in a subject comprising administration to the subject a therapeutically effective amount of at least one LTA4H modulator selected from compounds of the formula (II) according to claim 1 or its enantiomer, racemate or pharmaceutically acceptable salt.

9. The method of claim 8, where the specified R2and R3each independently selected from the group A).

10. The method of claim 8, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group consisting of i) and ii).

11. The method of claim 8, where these R2and R3taken together with the nitrogen to which they Preece is United, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group i).

12. The method of claim 8, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group ii).

13. The method of claim 8, where the specified LTA4H-mediated condition is an inflammation caused at least one of the diseases selected from asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

14. The method of claim 8, where specified, at least one LTA4H modulator is one of the compounds:
2-(4-piperidine-1-ylmethylene)benzoxazole and 2-(2-fluoro-4-piperidine-1-ylmethylene)benzoxazole.

15. The method of claim 8, where specified, at least one LTA4H modulator is one of the compounds:
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-it;
2-(2-fluoro-4-piperidine-1-and is methylphenoxy)benzothiazole;
1-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-it;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide;
2-{4-[4-(1H-tetrazol-5-yl)piperidine-1-ylmethyl]phenoxy}benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-it;
4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one;
2-(4-piperidine-1-ylmethylene)benzothiazole;
1-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanesulfonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-trifurcated;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
2-[4-(4-methanesulfonylaminoethyl-1-ylmethyl)phenoxy]benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline;
2-(4-(morpholine-4-yl is ethylenoxy)benzothiazole;
phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide;
ethyl ester of 3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
1-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-it;
[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine;
N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)isobutyramide;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-3-Isopropylamine;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-Isopropylamine;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydrox pyrrolidin-2-it;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-trifurcated;
2-[4-(1,1-diocletianopolis-4-ylmethyl)phenoxy]benzothiazole;
tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-utilmately;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide;
ethyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-propylacetic;
propyl ether {1-[4-(benzodi the evils-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metallocene;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloctane;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metallocene;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine;
isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloctane;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ester of acetic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea;
1'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipiperidine;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-(tetrahydrofuran-2-yl)methanone;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine;
2-(4-Pipera the Jn-1 ylmethylene)benzothiazole;
amide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
2-[4-(4-benzolsulfonate-1-ylmethyl)phenoxy]benzothiazole;
C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
2-(2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-oxoethyl)Cyclopentanone;
ethyl ester {4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
4-(benzothiazol-2-yloxy)benzyl ester 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyric acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)pyrrolidin-2-it;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)carbamino acid;
(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)amide tetrahydrofuran-2-carboxylic acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-4-hydroxypyrrolidine-2-it;
tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino }ethyl) - carbamino acid;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide econsultancy acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrole-2,5-dione;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}meth is lamina;
1-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-carboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methylamine;
benzothiazol-2-yl{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amine;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)carbamino acid;
4-({[4-(benzothiazol-2-yloxy)benzyl]methylamino}methyl)phenol;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-methylpropane-1,3-diamine;
(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propellerblades)methyl ester acetic acid;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-2-hydroxyacetamido;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)methanesulfonamide;
6-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
6-methoxy-2-(4-piperidine-1-ylmethylene)benzothiazole;
dimethylamide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-sulfonic acid;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-pyrrolidin-1 ratanana;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-morpholine-4-ratanana;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}thiophene-2-ylmethanone;
4-methyl-2-(4-piperidine-1-ylmethylene)benzothiazole;
4-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
2-[4-(4,4-deformability-1-ylmethyl)phenoxy]benzothiazole;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanol key is lots;
[4-(benzothiazol-2-yloxy)benzyl]methyl(1-methylpiperidin-4-yl)amine;
3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propionitrile;
4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-it;
2-[4-(3-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamoyl)methyl ester acetic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxy-N-methylacetamide and ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid.

16. A method of treating, preventing or inhibiting inflammation in a subject comprising administration to the subject a therapeutically effective amount of at least one LTA4H modulator selected from compounds of the formula (II) according to claim 1 or its enantiomer, racemate or pharmaceutically acceptable salt.

17. The method according to clause 16, where the specified R2and R3each independently selected from the group A).

18. The method according to clause 16, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group consisting of i) and ii).

19. The method according to clause 16, where these R2and R3taken together with the nitrogen to which they are also dinani, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group i).

20. The method according to clause 16, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group ii).

21. The method according to clause 16, where the specified inflammation is associated with at least one of the diseases selected from asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

22. The method according to clause 16, where specified, at least one LTA4H modulator is one of the compounds:
2-(4-piperidine-1-ylmethylene)benzoxazole and 2-(2-fluoro-4-piperidine-1-ylmethylene)benzoxazole.

23. The method according to clause 16, where specified, at least one LTA4H modulator is one of the compounds:
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-it;
2-(2-fluoro-4-piperidine-1-ylmethylene)benzothiazole;
1-(2-{[4-(benzothiazol-2-and the hydroxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-it;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide;
2-{4-[4-(1H-tetrazol-5-yl)piperidine-1-ylmethyl]phenoxy}benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-it;
4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one;
2-(4-piperidine-1-ylmethylene)benzothiazole;
1-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanesulfonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-trifurcated;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
2-[4-(4-methanesulfonylaminoethyl-1-ylmethyl)phenoxy]benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline;
2-(4-(morpholine-4-ylmethylene)benzothiazole;
phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]Piperi the Jn-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide;
ethyl ester of 3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
1-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-it;
[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine;
N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)isobutyramide;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-3-Isopropylamine;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-Isopropylamine;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea;
N-{1-[4-(benzo is a thiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-trifurcated;
2-[4-(1,1-diocletianopolis-4-ylmethyl)phenoxy]benzothiazole;
tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl }carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-utilmately;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide;
ethyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-propylacetic;
propyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metallocene;
1-{1-4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloctane;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metallocene;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine;
isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloctane;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ester of acetic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea;
1'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipiperidine;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-(tetrahydrofuran-2-yl)methanone;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]-piperidine-4-yl}carbamino acid;
tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine;
2-(4-piperazine-1-ylmethylene)benzothiazole;
amide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
2-[4-(4-benzosulfimide the Jn-1-ylmethyl)phenoxy]benzothiazole;
C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
2-(2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-oxoethyl)Cyclopentanone;
ethyl ester {4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
4-(benzothiazol-2-yloxy)benzyl ester 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl{butyric acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)pyrrolidin-2-it;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)carbamino acid;
(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)amide tetrahydrofuran-2-carboxylic acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-4-hydroxypyrrolidine-2-it;
tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cycle of propylamino}ethyl) - carbamino acid;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide econsultancy acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrole-2,5-dione;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
1-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-carboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methylamine;
benzothiazole-2-yl-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amine;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)carbamino acid;
4-({[4-(benzothiazol-2-yloxy)benzyl]methylamino}methyl)phenol;
N-[4-(benzothiazol-2-yloxy)benzyl]-N-methylpropan-1,3-diamine;
(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propellerblades)methyl ester acetic acid;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-2-hydroxyacetamido;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)methanesulfonamide;
6-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
6-methoxy-2-(4-piperidine-1-ylmethylene)benzothiazole;
dimethylamide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-sulfonic acid;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-pyrrolidin-1 ratanana;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-morpholine-4-ratanana;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}thiophene-2-ylmethanone;
4-methyl-2-(4-piperidine-1-ylmethylene)benzothiazole;
4-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
2-[4-(4,4-deformability-1-ylmethyl)phenoxy]benzothiazole;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methyl(1-methylpiperidin-4-yl)amine;
3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propionitrile;
4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-it;br/> 2-[4-(3-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamoyl)methyl ester acetic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxy-N-methylacetamide and ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid.

24. The method according to clause 16, where the specified LTA4H-mediated condition is an inflammation caused at least one of the diseases selected from asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

25. A method of inhibiting the activity of LTA4H enzyme, including the impact on the LTA4H enzyme inhibiting amount of at least one LTA4H modulator selected from compounds of the formula (II) according to claim 1 or its enantiomer, racemate or pharmaceutically acceptable salt.

26. The method according A.25 where the specified R2and R3each independently selected from the group A).

27. The method according A.25, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group status is the present of i) and ii).

28. The method according A.25, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group i).

29. The method according A.25, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group ii).

30. The method according A.25, where the specified LTA4H-mediated condition is an inflammation caused at least one of the diseases selected from asthma, chronic obstructive pulmonary disease, atherosclerosis, rheumatoid arthritis, multiple sclerosis, inflammatory bowel disease and psoriasis.

31. The method according A.25, where specified, at least one LTA4H modulator is one of the compounds:
2-(4-piperidine-1-ylmethylene)benzoxazole and 2-(2-fluoro-4-piperidine-1-ylmethylene)benzoxazole.

32. The method according A.25, where specified, at least one LTA4H modulator represents one of the following connections:
1-[4-(benzothiazol-2-yloxy)benzyl]piperidin-4-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-it;
2-(2-fluoro-4-piperidine-1-ylmethylene)benzothiazole;
1-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-it;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide;
2-{4-[4-(1H-tetrazol-5-yl)piperidine-1-ylmethyl]phenoxy}benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-it;
4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one;
2-(4-piperidine-1-ylmethylene)benzothiazole;
1-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanesulfonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-trifurcated;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
2-[4-(4-methanesulfonylaminoethyl--ylmethyl)phenoxy]benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline;
2-(4-(morpholine-4-ylmethylene)benzothiazole;
phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide;
ethyl ester of 3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
1-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-it;
[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine;
N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)isobutyramide;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-3-Isopropylamine;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-Isopropylamine;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid;
1-{1-[4-(benzothiazol-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-trifurcated;
2-[4-(1,1-diocletianopolis-4-ylmethyl)phenoxy]benzothiazole;
tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl} carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-utilmately;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide;
ethyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
1-{1-[4-(benzothiazol-2-and the hydroxy)benzyl]piperidine-4-yl}-3-propylacetic;
propyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metallocene;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloctane;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metallocene;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine;
isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloctane;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ester of acetic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea;
1'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipiperidine;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-(tetrahydrofuran-2-yl)methanone;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazin the-1-carboxylic acid;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine;
2-(4-piperazine-1-ylmethylene)benzothiazole;
amide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
2-[4-(4-benzolsulfonate-1-ylmethyl)phenoxy]benzothiazole;
C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
2-(2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-oxoethyl)Cyclopentanone;
ethyl ester {4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
4-(benzothiazol-2-yloxy)benzyl ester 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyric acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)pyrrolidin-2-it;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)carbamino acid;
(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)amide tetrahydrofuran-2-carboxylic acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-4-hydroxypyrrolidine-2-it;
tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl) - carbamino acid;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide econsultancy acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrole-2,5-dione;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)b is nil]piperidine-4-yl}methylcarbamate acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
1-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-carboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methylamine;
benzothiazol-2-yl{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amine;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)carbamino acid;
4-({[4-(benzothiazol-2-yloxy)benzyl]methylamino}methyl)phenol;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-methylpropane-1,3-diamine;
(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propellerblades)methyl ester acetic acid;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-2-hydroxyacetamido;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)methanesulfonamide;
6-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
6-methoxy-2-(4-piperidine-1-ylmethylene)benzothiazole;
dimethylamide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-sulfonic acid;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-pyrrolidin-1 ratanana;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-morpholine-4-ratanana;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}thiophene-2-ylmethanone;
4-methyl-2-(4-piperidine-1-ylmethylene)benzothiazole;
4-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
2-[4-(4,4-deformability-1-ylmethyl)phenoxy]benzothiazole;
{1-[4-(benzothiazol-2-yloxy)Ben who yl]piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methyl(1-methylpiperidin-4-yl)amine;
3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propionitrile;
4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-it;
2-[4-(3-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
({1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamoyl)methyl ester acetic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxy-N-methylacetamide and ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid.

33. Pharmaceutical composition having the property of inhibitor leukotriene A4-hydrolases (LTA4H), containing a therapeutically effective amount of at least one compound of the formula (II) according to claim 1 or its enantiomer, racemate or pharmaceutically acceptable salt.

34. The pharmaceutical composition according p, where these R2and R3each independently selected from the group A).

35. The pharmaceutical composition according p, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group consisting of i) and ii).

36. The pharmaceutical composition according p, where these R2and R3taken the e together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group i).

37. The pharmaceutical composition according p, where these R2and R3taken together with the nitrogen to which they are attached, form a heterocyclic ring which contains at least one heteroatom, which is a specified nitrogen accession, and this heterocyclic ring selected from the group ii).

38. The pharmaceutical composition according p, where the aforementioned at least one compound of the formula (II) represents one of:
2-(4-piperidine-1-ylmethylene)benzoxazole and 2-(2-fluoro-4-piperidine-1-ylmethylene)benzoxazole.

39. The pharmaceutical composition according p, where the aforementioned at least one compound of the formula (II) represents one of:
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrolidin-2-it;
2-(2-fluoro-4-piperidine-1-ylmethylene)benzothiazole;
1-(2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl)-4-hydroxypyrrolidine-2-it;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylmethanesulfonamide;
2-{4-[4-(1H-tetrazol-5-yl)piperidine-1-elmet the l]phenoxy}benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2-hydroxyethane;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}methanesulfonamide;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}oxazolidin-2-it;
4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}morpholine-3-one;
2-(4-piperidine-1-ylmethylene)benzothiazole;
1-[4-(benzothiazol-2-yloxy)benzyl]-4-phenylpiperidine-4-ol;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ol;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanol;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methanesulfonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2-hydroxyacetamido;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}-2,2,2-trifurcated;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
2-[4-(4-methanesulfonylaminoethyl-1-ylmethyl)phenoxy]benzothiazole;
1-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-2,2,2-triptoreline;
2-(4-(morpholine-4-ylmethylene)benzothiazole;
phenyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}benzosulfimide;
ethyl ester of 3-[4-(benzothiazol-2-ilok and)benzoylamino]propionic acid;
3-[4-(benzothiazol-2-yloxy)benzoylamino]propionic acid;
1-{3-[4-(benzothiazol-2-yloxy)benzylamino]propyl}pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]isopropylamino}propyl)pyrrolidin-2-it;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]ethylamino}propyl)pyrrolidin-2-it;
[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamine;
N-1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylamino-1,3-diamine;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)isobutyramide;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-3-Isopropylamine;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-Isopropylamine;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}isobutyramide;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide tetrahydrofuran-2-carboxylic acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-4-hydroxypyrrolidine-2-it;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}urea;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}assalamou acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxyacetamido;
N-{1-[4-(benzodiaz the l-2-yloxy)benzyl]piperidine-4-yl}-2,2,2-trifurcated;
2-[4-(1,1-diocletianopolis-4-ylmethyl)phenoxy]benzothiazole;
tert-butyl ether N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-aminosulfonyl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}ndimethylacetamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N,N-dimethylsulfide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-utilmately;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-ethylthiophene;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-1-sulfonic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide propane-2-sulfonic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}sulphonamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}formamide;
ethyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}propionamide;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyramide;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-propylacetic;
propyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-3-metallocene;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,3-dimethyloctane;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1-metallocene;
N-{1-[4-(benzo is a thiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methylacetamide;
methyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
methyl ester of N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N-methoxylamine acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-N'-hydroxyguanidine;
isopropyl ether {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
3-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-1,1-dimethyloctane;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylcarbonyl}methyl ester of acetic acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}thiourea;
1'-[4-(benzothiazol-2-yloxy)benzyl]-[1,4']bipiperidine;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-(tetrahydrofuran-2-yl)methanone;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}carbamino acid;
tert-butyl ester 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylamine;
2-(4-piperazine-1-ylmethylene)benzothiazole;
amide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-carboxylic acid;
2-[4-(4-benzolsulfonate-1-ylmethyl)phenoxy]benzothiazole;
C-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
2-(2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazin-1-yl}-2-oxoethyl)Cyclopentanone;
ethyl ester {4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}acetic acid;
4-(benzothiazol-2-yloxy)benzyl ester 4-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}butyric acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)pyrrolidin-2-it;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)carbamino acid;
(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)amide tetrahydrofuran-2-carboxylic acid;
1-(3-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}propyl)-4-hydroxypyrrolidine-2-it;
tert-butyl ether (2-{[4-(benzothiazol-2-yloxy)benzyl]cyclopropylamino}ethyl) - carbamino acid;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-cyclopropylidene-1,2-diamine;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amide econsultancy acid;
1-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}pyrrole-2,5-dione;
tert-butyl ester {1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylcarbamate acid;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}methylamine;
1-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-carboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methylamine;
benzothiazol-2-yl{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}amine;
tert-butyl methyl ether (3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)carbonintensity;
4-({[4-(benzothiazol-2-yloxy)benzyl]methylamino}methyl)phenol;
N1-[4-(benzothiazol-2-yloxy)benzyl]-N1-methylpropane-1,3-diamine;
(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}-propellerblades)methyl ester acetic acid;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-2-hydroxyacetamido;
N-(3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propyl)-methanesulfonamide;
6-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
6-methoxy-2-(4-piperidine-1-ylmethylene)benzothiazole;
dimethylamide 4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-sulfonic acid;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-pyrrolidin-1 ratanana;
2-{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}-1-morpholine-4-ratanana;
{4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-1-yl}thiophene-2-ylmethanone;
4-methyl-2-(4-piperidine-1-ylmethylene)benzothiazole;
4-chloro-2-(4-piperidine-1-ylmethylene)benzothiazole;
2-[4-(4,4-deformability-1-ylmethyl)phenoxy]benzothiazole;
{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-ylmethyl}amide 2-aminocyclohexanecarboxylic acid;
[4-(benzothiazol-2-yloxy)benzyl]methyl(1-methylpiperidin-4-yl)amine;
3-{[4-(benzothiazol-2-yloxy)benzyl]methylamino}propionitrile;
4-[4-(benzothiazol-2-yloxy)benzyl]piperazine-2-it;
2-[4-(3-methylpiperidin-1-ylmethyl)phenoxy]benzothiazole;
({1-[4-(benzothiazol-2-yloxy)benzyl]Pieper is DIN-4-yl}methylcarbamoyl)methyl ester acetic acid;
N-{1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-yl}-2-hydroxy-N-methylacetamide, and
ethyl ester 1-[4-(benzothiazol-2-yloxy)benzyl]piperidine-4-carboxylic acid.



 

Same patents:

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: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of derivatives of indolinospiropyrane of the formula (1): wherein R1 means (C1-C18)-alkyl; each among R2 and R3 mean independently (C1-C4)-alkyl; R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl formyl, (C1-C)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2. Method comprises the following steps: (i) synthesis of indoline on polymeric carrier of the formula (III): wherein R1 means (C1-C18)-alkyl; each among R2 and R means independently (C1-C4)-alkyl; (ii) treatment of indoline-carrying polymeric carrier wherein this carrier represents hydroxy-resin at temperature from 50°C to 120°C in inert atmosphere for time from 14 h to 11 days with a derivative of salicylic aldehyde of the formula (VI): wherein R4 means hydrogen atom, hydroxy-group, trichloromethyl, trifluoromethyl, formyl, (C1-C4)-alkyl, halogen atom, (C1-C4)-alkoxy-, nitro-group; x = 1 or 2 to yield indolinospiropyrane compound of the formula (I), and (iii) release of indolinospiropyrane compound of the formula (I). Invention proves synthesis of novel derivatives of indolinospiropyrane possessing photochromic properties.

EFFECT: improved method of synthesis.

8 cl, 28 ex

FIELD: organic chemistry.

SUBSTANCE: invention describes C2-phenyl-substituted cyclic ketoenols of the general formula: wherein W means hydrogen atom, alkyl with 1-6 carbon atoms; X means alkyl with 1-6 carbon atoms, alkenyl with 2-6 carbon atoms; Y means hydrogen atom, methyl, ethyl, isopropyl, alkenyl with 2-6 carbon atoms, ethynyl; Z means hydrogen atom, alkyl with 1-6 carbon atoms under condition that at least one of residues W, X, Y or Z means a chain with at least 2 carbon atoms but only one of residues X and Y can mean alkenyl with 2-6 carbon atoms; CKE means one of the following groups: , , and wherein A means hydrogen atom, alkyl with 1-6 carbon atoms; B means hydrogen atom, alkyl with 1-6 carbon atoms; A and B in common with carbon atom to which they are bound mean cycloalkyl with 5-6 carbon atoms wherein the ring carbon atom can be substituted with oxygen atom and can be substituted with alkyl with 1-6 carbon atoms or alkoxyl with 1-6 carbon atoms; A and B in common mean group of the formula: D means hydrogen atom or phenyl substituted with fluorine atom if CKE means group of the formula (4); G means hydrogen atom (a) or one of groups of the formula: or wherein R1 means alkyl with 1-6 carbon atoms, alkoxymethyl with 1-2 carbon atoms; R2 means alkyl with 1-4 carbon atoms; A and Q1 in common mean alkanediyl with 3-4 carbon atoms; Q2 means hydrogen atom. Invention provides preparing compound of the formula (I) possessing with insecticide, acaricide and herbicide activity.

EFFECT: valuable properties of compounds.

2 cl, 8 tbl, 32 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention proposes derivative of 3,4-dihydroisoquinoline of the formula (I) or its nontoxic salt and a pharmaceutical agent comprising its as an active component (wherein all symbols have the same values as given in description). Compound of the formula (I) possesses agonistic effect on CB2-receptors and, therefore, it can be used for prophylaxis and/or treatment of different diseases, for example, asthma, nasal allergy, atopic dermatitis, autoimmune diseases, rheumatic arthritis, immune dysfunction, postoperative pain and carcinomatous pain.

EFFECT: valuable medicinal properties of derivatives.

14 cl, 33 tbl, 561 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, nitro group, acyl group, amido group, alkylamido group, amido group dialkyl, carboxyl group, saturated, unsaturated or partially saturated mono- or dicyclic 5-10-meroud ring optionally substituted with one or more groups, chosen of alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkyloxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, dialkylamido group, carboxyl group, or alkyl (1-3C) group substituted with saturated, unsaturated or partially saturated five- or hexamerous ring optionally containing one or more heteroatoms, such as nitrogen atom, oxygen atom or sulphur atom, optionally substituted with one or more groups chosen from alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkyloxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, dialkylamido group, carboxyl group, or (R3+R4) together with nitrogen atom, they are attached to, represent saturated, unsaturated or partially saturated mono- or dicyclic five- or hexamerous ring optionally containing one or more heteroatoms, such as nitrogen atom, oxygen atom or sulphur atom, optionally substituted with one or more groups chosen of alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkyloxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, dialkylamido group, carboxyl groups, as well as to all stereoisomers, to pharmaceutically acceptable salts. Additionally, the invention concerns pharmaceutical compositions and application of compounds.

EFFECT: production of new biologically active compounds with agonist activity to ORL1 receptors.

9 cl, 488 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula where A-B stands for CH2-CH2, -CH2-O-, -O-CH2-, -CH2-S-, -S-CH2-, -N(R4)-CH2- or -CH2-N(R4)-; R1 stands for (lower)alkyl, (lower)alkenyl, cycloalkyl or stands for aryl, optionally substituted with one or two substitutes chosen from the group consisting of haloid, cyano, (lower)alkyl, CF3, OCF3 or (lower)alkoxy, or stands for heteroaryl representing cyclic aromatic hydrocarbon radical containing one or two heteroatoms chosen of the group consisting of sulphur or nitrogen, e.g. thiazolyl or thienyl, optionally substituted with one or two substitutes chosen from (lower)alkyl; R2 stands for (lower)alkyl, cycloalkyl or stands for aryl, optionally substituted with one or two substitutes chosen from the group consisting of haloid, (lower)alkyl, CF3, (lower)alkoxy, or stands for heteroaryl representing cyclic aromatic hydrocarbon radical containing one sulphur heteroatom, e.g. thienyl; R3 stands for hydrogen; R4 stands for hydrogen or benzyl; n stands for 0, 1 or 2; and to their pharmaceutically acceptable salts. Besides, the invention concerns a medical product.

EFFECT: production of new biologically active compounds inhibiting glycine carrier 1 (GlyT-1).

19 cl, 59 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 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 th