Novel cyclic hydrocarbon compounds for treatment of diseases


FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel cyclic compounds of general formula which possess properties of CaSR modulator. In general formula I group represents cycloalkyl, which contains 4-7 carbon atoms, optionally substituted with one or several similar or different substituents, selected from R2, R3, R4 or R5; A represents 1-naphthyl; R1 represents methyl, ethyl or n-propyl, each of which is optionally substituted with one or several, similar or different substituents, selected from halogen and hydroxy; R2 and R3 represent hydrogen; R4 represents hydrogen, halogen, hydroxy or C1-6alkyl; each R5 represents independently one or several similar or different substituents, represented by hydrogen or C1-6alkyl; G represents -C(O)NH2, C3-8cycloalkyl, C1-6heterocycloalkyl, C1-6heterocycloalkenyl, C3-8cycloalkenyl, C6-14aryl, C1-10heteroaryl, C6-10arylamino, hydroxyaminocarbonyl, C6-10arylaminocarbonyl, C1-4aminocarbonyl, C1-6heterocycloalkylcarbonyl, C1-10heteroarylaminocarbonyl, C6-10arylsulfonylaminocarbonyl, C6-14aryloxy, or C1-4alkoxycarbonyl, where said substituents are optionally additionally substituted with one or several, similar or different substituents. Other values of radicals are given in the formula of invention.

EFFECT: compounds can be applied in treatment, relief or prevention of physiological disorders or diseases, associated with impairment of activity of CaSR, such as hyperparathyreosis, and other diseases.

23 cl, 9 dwg, 3 tbl, 315 ex

 

The SCOPE of the INVENTION

This invention relates to new cyclic hydrocarbon compounds and their derivatives, processes for their preparation, to said compounds for use as pharmaceuticals, to said compounds for use in therapy, to pharmaceutical compositions containing these compounds, to methods of treatment of diseases of these compounds and to the use of these compounds for the production of medicines.

The LEVEL of TECHNOLOGY

Susceptible to calcium receptor (CaSR) is associated with G-protein receptor (GPCR), which signals through activation of phospholipase C, increasing the levels of Inositol 1,4,5-triphosphate and cytosolic calcium. CaSR belongs to the subfamily C of the GPCR superfamily, which also includes receptors of glutamate, gamma-aminobutyric acid (GABA), pheromones and odorants, which all have a very large extracellular domain. This domain carries a strong negative charge and is involved in the binding of calcium and other positively charged molecules. CaSR found in the parathyroid glands, but have also been identified in the brain, intestine, pituitary gland, thyroid glands, bone and kidneys. In the parathyroid glands CaSR is activated when a small increase in extracellular ionized calcium, which ingibiruet the release of the hormone parathyroid (PTH), stored in intracellular granules [Brown, E. M. Calcium-Sensing Receptor.Primer of the Metabolic Bone Diseases and Disorders of Mineral Metabolism,Fifth Edition, 2003 by American Society for Bone and Mineral Research, Chapter 17, p. 111.; Drueke, T. E.Nephrol Dial Transplant(2004) 19, v20-v26].

In addition to endogenous ligands developed small molecular allosteric activators CaSR ("calcimimetic") [Urena, P.; Frazao, J. M. Calcimimetic agents: Review and perspectives.Kidney International(2003), 63, pp. s91-s96; Soudijn, W. et al. Allosteric modulation of G protein-coupled receptors: perspectives and recent developments. DDT (2004), 9, 752-758].

The binding site of known calcimimetics, probably, is in the seventh TRANS-membrane domain of the receptor [Petrel, C. et al.Journal of Biological Chemistry(2004), 279, 18990-18997].

Calcimimetic, as already shown, are commercially applicable for treatment of hyperparathyroidism (HPT): Calcimimetics connection Cinacalcet® [Balfour, J. A. B., et al.Drugs(2005) 65(2), 271-281; Linberg et. al.J. Am. Soc. Nephrol(2005), 16, 800-807, Clinical Therapeutics (2005), 27(11), 1725-1751] recently approved for the treatment of secondary HPT in patients with chronic kidney disease with dialysis and for the treatment of primary HPT in patients with cancer of the parathyroid gland.

Thus, the proof of concept activators sensitive to the calcium receptor (CaSR) in humans, are obtained, and the clinical significance is already well established. Chronic kidney disease hypocalcaemia is a result of a breach on the stop of renal phosphorus and low education l,25(OH) 2-VitD. In response, increases the secretion of PTH, resulting in a condition known as secondary HPT. Primary HPT is hypercalcemic disorder, which occurs due to excessive secretion of PTH, usually caused by an adenoma of the parathyroid gland or primary hyperplasia of the parathyroid gland. Other calcimimetics compounds have been described, for example, in WO 94/018959, W098/001417, WO05/065050, WO03/099814, WO03/099776, WOOO/21910, WO01/34562, WO01/090069, WO97/41090, US 6001884, WO96/12697, EP1203761, WO95/11221, WO93/04373, EP1281702, WO02/12181, WO04/069793, US 2004242602, WO04/106296 and WO05/115975.

Calcimimetics activity corresponds to the ability to produce or to cause the biological responses observed through changes in the concentration of extracellular calcium ions (Ca2+)eand extracellular magnesium ions (Mg2+)e.

Ions (Caz+)eand Mg2+)eplay an important role in the body, as they regulate calcium homeostasis which affects the vital functions of the body. So, Hypo - and hypercalcemia, i.e. the state in which the content of ions (Ca2+)ebelow or above the average threshold values have a significant impact on many functions, such as cardiac, renal or intestinal function. They deeply affect the Central nervous system [Chattopadhyay et al.Endocr. Review,(1998)].

The receptor CaSR are be the kami, which are sensitive to ions (Ca2+)eand Mg2+)eand present in the parathyroid and thyroid glands, kidney, intestine, lung, bone cells, brain, spinal cord, hypophysis, stomach and keratinocytes [Brown et al.,Nature,(1993); Ruat et al.,Proc. Natl. Acad. Sci.,USA, (1995); Brown et al.,Ann. Rev, Med.,(1998)]. These proteins are encoded by a single gene, isolated from various animal species. They belong to the family associated with G-protein receptors with seven TRANS-membrane domains and detect structural homology with metabotropic glutamate receptors, GABA receptors and hypothetical feromonami and taste buds. Activating or inhibiting gene mutation in humans is responsible for very serious genetic diseases that cause hypocalcaemia or hypercalcemia [Pollack et al.,Cell,(1993); Pollack et al.,Nature Genetic,(1994); Brown et al.,Ann. Rev. Med.,(1998)]. Functions associated with the expression of these proteins in tissues, yet not all are known and are the subject of considerable research activity, especially in the receptor CaSR present in the parathyroid and thyroid glands, kidney, intestine, spinal cord, brain, and bone cells.

In the parathyroid gland receptors CaSR modulate the secretion of parathyroid hormone (PTH), which is the main Regulus is a torus of calcium homeostasis: the increase in the content of ions (Ca 2+)eserum will activate the receptor CaSR present on cells of the parathyroid gland, and reduce the secretion of the hormone PTH.

Complementary DNA encoding rat CaSR, selected from a library of rat veins cDNA [Ruat et al.,Proc. Natl.Acad.Sci.,(1995)]. This receptor is identical, in terms of its amino acid sequence, the receptor expressed in other tissues. Subjected to transfection the cells of the Chinese hamster ovary (CHO)expressing rat CaSR (CHO(CaSR), have been characterized, and chemical signals (secondary messengers), activation-induced specified receptor, were analyzed. So, was developed biochemical test for measuring the accumulation of tritium-labeled Inositol phosphates, [3H]IP, in response to activation of the receptor [Ruat et al., J.Biol. Chem.,(1996); Ferry et al.,Biochem. Biophys. Res. Common.,(1997)].

It was shown that ions of Ca2+and Mg2+and ions Ba2+within millimolar concentrations stimulate the receptor CaSR. Activation of the receptor CaSR could be induced in the brain β-amyloid peptides, which are involved in neurodegenerative diseases such as Alzheimer's disease [Ye et al.,J. Neurosci. Res.(1997)].

Violation of CaSR activity associated with biological disorders, such as primary and secondary hyperparathyroidism, OST is operas, cardiovascular, gastrointestinal, endocrine and neurodegenerative diseases or certain types of malignant tumors, in which the content of ions (Ca2+)eis abnormally high.

Secondary hyperparathyroidism is observed in chronic renal failure and is characterized by hyperplasia of the parathyroid glands and increased levels of circulating PTH. Renal failure is also accompanied by renal osteodystrophy, for example, fibrous generalized acticom, disorder, adinamicheskoy bone disease or osteoporosis. Disorder characterized by or high or low renewal of bone tissue.

Osteoporosis is a multifactorial disease, which depends, in particular, by age and sex. Very affecting menopausal women, osteoporosis is becoming an increasing problem for older men, and at the moment there is no really satisfactory way of treatment. Its social significance may even become heavier over the years, especially in our European society, where life expectancy becomes longer. Osteoporosis currently treated with estrogens, calcitonin or bifosfonatami that prevent bone resorption without stimulating bone growth. More than the recent data demonstrate that the periodical increase in the content of PTH or its derivatives is effective in the treatment of osteoporosis and make possible the reconstruction of bone by stimulating bone formation [Whitfield et al.,Drugs & Aging,(1999), Whitfield et al.,Calc. Tissue Int.,(1999)]. This new therapeutic approach to the treatment of osteoporosis is very attractive, although major problems associated with use of hormone PTH, such as the introduction of injection and the appearance of tumors observed recently in wide clinical studies in humans. Periodic secretion of endogenous PTH can be achieved by blocking sensitive to the calcium receptor. Blocking the secretion of PTH by the CaSR agonists may be accompanied by a rapid increase in the level of PTH (recoil effect), which is subsequently useful in the treatment of osteoporosis.

The INVENTION

This invention relates to new cyclic hydrocarbon compounds having effects of modulation sensitive to the calcium receptor (CaSR). Unexpectedly, it was found that cyclic hydrocarbon compounds in this invention are modulators, e.g., activators or agonists that are sensitive to calcium receptor human (CaSR) and therefore can be applied in the treatment or prevention of certain diseases or physiological destroy the TV involving modulation of CaSR activity.

Cyclic hydrocarbon compounds according to this invention can, for example, be applicable in the treatment of complications associated with chronic kidney disease such as hyperparathyroidism, for example, primary and/or secondary hyperparathyroidism tertiary hyperparathyroidism. Other complications associated with chronic pocetnymi disease, anemia, cardiovascular disease, associated with podocyte dysfunction, such as proteinuria, atrophy of the renal tubules or podocytopenia, and compounds in this invention, it is believed, also have a beneficial effect in these diseases. Cyclic hydrocarbon compounds according to this invention may also be applicable for promotion of osteogenesis and treatment or prevention of osteoporosis, such as that induced by steroids osteoporosis, senile osteoporosis and post-menopausal osteoporosis, osteomalacia and related disorders of bone tissue or to prevent bone loss after kidney transplant or rescue operations removal of the parathyroid glands.

Now consider that cyclic hydrocarbon compounds according to this invention may be useful pharmacokinetic or pharmacodynamic properties, such as bioavailability when administered orally, in comparison with the known structure of the but related compounds.

Accordingly, this invention relates to the compound of General formula I

,

where the groupis cycloalkyl containing 4-7 carbon atoms, optionally substituted by one or more, same or different substituents selected from R2, R3, R4or R5;

A represents A C1-10heteroaryl,6-14aryl or C6-10heterocollateral,each of which is optionally substituted by one or more identical or different substituents, such as halogen, hydroxy, mercapto, trifluoromethyl, cyano, carboxy, -NH2, -C(O)MHZ, nitro, oxo, -S(O)2NH2C1-4alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4aminocarbonyl, C1-4alkylthio, C3-8cycloalkyl, C3-8cycloalkenyl, C1-6amino, aminomethyl, C1-4aminosulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonamides, gidroksilaminami, C1-4alkylcarboxylic, C1-4alkylsulfonyl, C1-6heteroseksualci, C1-6geteroseksualen, C1-10heteroaryl or 6-14aryl,

where specified C1-4alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4aminocarbonyl, C1-4alkylthio, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6amino, aminomethyl, C1-4aminosulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonamides, gidroksilaminami, C1-4alkylcarboxylic, C1-4alkylsulfonyl, C1-6heteroseksualci, C1-6geteroseksualen, C1-10heteroaryl or C6-14aryl

optionally additionally substituted by one or more, same or different substituents selected from halogen, hydroxy, -NH2, mercapto, trifloromethyl, cyano, carboxy, -C(O)NH2, nitro, oxo, -S(O)2NH2C1-4of alkyl, C1-6halogenoalkane, C1-3alkoxy or C1-3hydroxyalkyl;

R1represents C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, C1-6alkylamino, C3-6cycloalkyl or C1-6heteroseksualci,

each of which is optionally substituted by one or more identical or different substituents, select nimi from halogen, hydroxy, mercapto, trifloromethyl, cyano, carboxy, NH2, -C(O)NH2, nitro, oxo, C1-3of alkyl, C2-4alkenyl, C1-3hydroxyalkyl, C1-3halogenoalkane, C1-4alkoxy, C1-4alkoxycarbonyl or C1-4amino;

R2and R3independently of one another represent hydrogen, cyano, halogen, carboxy, -C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, aminos1-6alkyl, C3-6cycloalkyl, C1-6heteroseksualci, C1-6alkoxy, C1-6aminocarbonyl, C6-10aryloxyalkyl, C1-6amino, C6-10arylamino, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C2-4alkenylamine, c3-6cycloalkylcarbonyl or C1-6geterotsiklicheskikh,

where specified-C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, aminos1-6alkyl, C3-6cycloalkyl, C1-6heteroseksualci, C1-6alkoxy, C1-6aminocarbonyl, C6-10aryloxyalkyl, C1-6amino, C6-10arylamino, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C2-4alkenylamine, C3-6cycloalkylcarbonyl or C1-6geterotsiklicheskikh

are neobyazatelnostyu one or more, identical or different substituents, such as halogen, hydroxy, mercapto, trifluoromethyl, cyano, carboxy, -NH2, -C(O)NH2, nitro, C1-3alkyl, C2-4alkenyl, C1-3hydroxyalkyl, C1-3halogenated, C1-4alkoxy, C1-4alkoxycarbonyl or C1-4amino;

R4represents hydrogen, halogen, hydroxy, carboxy, -NH2, -C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, aminos1-6alkyl, C3-6cycloalkyl, C1-6heteroseksualci, C1-6alkoxy, C1-6alkoxycarbonyl, C1-6aminocarbonyl, C6-10aryloxyalkyl, C1-10heteroarylboronic, C1-6amino, C6-10arylamino, C1-10heteroarenes, C6-10arils1-6amino, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C2-4alkenylamine, C3-6cycloalkylcarbonyl or C1-6geterotsiklicheskikh,

where specified-C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, aminos1-6alkyl, C3-6cycloalkyl, C1-6heteroseksualci, C1-6alkoxy, C1-6alkoxycarbonyl, C1-6aminocarbonyl, C6-10aryloxyalkyl, C1-10heteroarylboronic, C1-6Amin is, C6-10arylamino, C1-10heteroarenes, C6-10arils1-6amino, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C2-4alkenylamine, C3-6cycloalkylcarbonyl or C1-6geterotsiklicheskikh

are optionally substituted by one or more, same or different substituents represented by halogen, hydroxy, mercapto, trifluoromethyl, cyano, carboxy, -NH2, gidroxiizomera, -C(O)NH2, nitro, C1-3the alkyl, C2-4alkenyl, C1-3hydroxyalkyl, C1-3halogenation, C1-4alkoxy, C1-4alkoxycarbonyl or C1-4amino;

each R5is independently one or more identical or different substituents, such as hydrogen, halogen, hydroxy, carboxy, -NH2, -C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, C3-6cycloalkyl, C1-6heteroseksualci, C1-6alkoxy, C1-4alkoxycarbonyl, C1-6aminocarbonyl, C6-10aryloxyalkyl, C1-10heteroarylboronic, C1-6amino, C6-10aryl, C6-10arylamino, C1-10heteroarenes, C6-10arylcarboxamide, C1-4alkoxycarbonyl, C6-10arylsulfonamides, C1-4alkylborane is amino, C2-4alkenylamine, C3-6cycloalkylcarbonyl or C1-6geterotsiklicheskikh,

where specified C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, C3-6cycloalkyl, C1-6heteroseksualci, C1-6alkoxy, C1-4alkoxycarbonyl, C1-6aminocarbonyl, C6-10aryloxyalkyl, C1-10heteroarylboronic, C1-6amino, C6-10aryl, C6-10arylamino, C1-10heteroarenes, C6-10arylcarboxamide, C1-4alkoxycarbonyl, C6-10arylsulfonamides, C1-4alkylcarboxylic, C2-4alkenylamine, C3-6cycloalkylcarbonyl or C1-6geterotsiklicheskikh

are optionally additionally substituted by one or more, same or different substituents selected from halogen, hydroxy, mercapto, cyano, trifloromethyl, carboxy, -NH2, -C(O)NH2, nitro, oxo, C1-3of alkyl, C2-4alkenyl, C1-3hydroxyalkyl, C1-3halogenoalkane, C1-4alkoxy, C1-4alkoxycarbonyl, iminomethyl or gidroxiizomera;

G is hydrogen, -C(O)H, -C(O)NH2, -O-C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, C1-6amino, C3-8 cycloalkyl, C1-6heteroseksualci, C1-6geteroseksualen, C3-8cycloalkenyl, C6-14aryl, C1-10heteroaryl, C6-10arylamino, hydroxyaminobuteroyl, C6-10allumination, C1-4aminocarbonyl, C1-6geterotsiklicheskikh, C1-10heteroarylboronic, C6-10arylsulfonamides, C6-14aryloxy, C1-10heteroaromatic, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-6aminocarboxylate, C1-10heteroarenes, C1-3alkylcarboxylic, C6-10arylcarboxamide, C3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl, C1-6geterotsiklicheskikh or ureido,

where specified-C(O)H, -C(O)NH2, -O-C(O)NH2C1-6alkyl, C2-6alkenyl, C2-6quinil, C1-6hydroxyalkyl, C1-6halogenated, C1-6amino, C3-8cycloalkyl, C1-6heteroseksualci, C1-6geteroseksualen, C3-8cycloalkenyl, C6-14aryl, C1-10heteroaryl, C6-10arylamino, hydroxyaminobuteroyl, C6-10allumination, C1-4aminocarbonyl, C1-6geterotsiklicheskikh, C1-10heteroarylboronic, C6-10arylsulfonamides, C6-14aryloxy, C1-10heteroaromatic, C1-4alkoxy, Csub> 1-4alkoxycarbonyl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-6aminocarboxylate, C1-10heteroarenes, C1-3alkylcarboxylic, C6-10arylcarboxamide, C3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl, C1-6geterotsiklicheskikh or ureido

are optionally additionally substituted by one or more identical or different substituents, such as halogen, cyano, carboxy, -NH2C1-6amino, aminomethyl, gidroksilaminami, amidino, hydroxy, mercapto, -C(O)H, -C(O)NH2, nitro, oxo, trifluoromethyl, C1-6alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, amino1-3alkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C1-4aminocarbonyl, hydroxyaminobuteroyl, C3-6cycloalkylcarbonyl, C1-6heterocyclizations, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6cyclooctylamino, C1-6heteroseksualci, C1-6geteroseksualen, C1-6geterotsiklicheskikh, C6-14aryl, carboxy6-10aryl, C1-6heteroaryl, C1-6heteroarylboronic, -S(O)2NH2C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic, C1-4alkoxycarbonyl is lexi, C1-4alkoxycarbonyl, C1-6heterocyclizations, C1-4alkylthio, C1-4aminosulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonyl, C6-10arylamino, C6-10allumination, C6-10aryloxyalkyl, C1-4alkoxycarbonyl, C6-10arylcarboxamide, C6-10arylsulfonamides, C1-4alkylcarboxylic, C1-4alkenylamine, C3-6cycloalkylcarbonyl, C3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl, C1-6geterotsiklicheskikh, C1-4alkylsulfonyl, C1-6heterocyclisation or C1-3alkylsulfonamides,

where specified carboxy, C1-6amino, aminomethyl, gidroksilaminami, -C(O)NH2C1-6alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, amino1-3alkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C1-4aminocarbonyl, hydroxyaminobuteroyl, C3-6cycloalkylcarbonyl, C1-6heterocyclizations, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6cyclooctylamino, C1-6heteroseksualci, C1-6geteroseksualen, C1-6geterotsiklicheskikh, C6-14aryl, carboxy6-10aryl, C1-6heteroaryl, C1-6heteroarenes arbonyl, -S(O)2NH2C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-6heterocyclizations, C1-4alkylthio, C1-4aminosulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonyl, C6-10arylamino, C6-10allumination, C6-10aryloxyalkyl, C1-4alkoxycarbonyl, C6-10arylcarboxamide, C6-10arylsulfonamides, C1-4alkylcarboxylic, C1-4alkenylamine, C3-6cycloalkylcarbonyl, C3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl, C1-6geterotsiklicheskikh, C1-4alkylsulfonyl, C1-6heterocyclisation or C1-3alkylsulfonamides,

are optionally additionally substituted by one or more, same or different substituents selected from such as hydroxy, -NH2C1-6amino, aminomethyl, gidroksilaminami, carboxy, trifluoromethyl, halogen, oxo, mercapto, cyano, -C(O)NH2, nitro, C1-6alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-3alkoxy, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C3-8cycloalkyl, C3-8cycloalkenyl, C1-6heteroseksualci, C6-12Ari is, C1-10heteroaryl, C1-3alkoxyl6-10aryl, C1-10heterocollateral, C1-6geteroseksualen, -S(O)2NH2, -S(O)2OH, -S(O)2CH3C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4aminocarbonyl, C1-6geterotsiklicheskikh, C1-4alkylthio, C1-4aminosulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonyl, C6-14arylsulfonyl, C6-10arylsulfonamides, gidroksilaminami, C1-4alkylcarboxylic or C1-4alkylsulfonyl,

where specified-C(O)NH2C1-6amino, C1-6alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-3alkoxy, C1-4alkoxycarbonyl, C3-8cycloalkyl, C3-8cycloalkenyl, C1-6heteroseksualci, C6-12aryl, C1-10heteroaryl, C1-3alkoxyl6-10aryl, C1-10heterocollateral, C1-6geteroseksualen, -S(O)2NH2, -S(O)2OH, C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4aminocarbonyl, C1-6geterotsiklicheskikh, C1-4alkylthio, C1-4AMI is sulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonyl, C6-14arylsulfonyl, C6-10arylsulfonamides, gidroksilaminami, C1-4alkylcarboxylic or C1-4alkylsulfonyl

are optionally additionally substituted by one or more, same or different substituents selected from such as hydroxy, oxo, cyano, halogen, trifluoromethyl, C1-3alkoxy, C1-3alkoxyl1-3alkoxy, C1-6amino, mercapto, carboxy, -C(O)NH2, nitro, C1-6alkyl, C1-3hydroxyalkyl, C1-4alkoxycarbonyl, C1-3alkylcarboxylic, C1-6heteroseksualci, C6-12aryl, C1-6heteroaryl, -S(O)2NH2or-S(O)2OH;

or G with R4forms oxoprop;

provided that the connection is not the same as

N-cyclopentyl-α-methylbenzeneethanamine,

N-cyclohexyl-α-methylbenzeneethanamine,

3-[3-[(1-phenylethyl)amino]cyclohexyl]phenol,

2-[3-[3-[(1-phenylethyl)amino]cyclohexyl]phenoxy]ethyl ester acetic acid,

N-[3-(3-methoxyphenyl)cyclohexyl]-α-methyl-2-naphthalenemethanamine,

N-[3-(3-methoxyphenyl)cyclohexyl]-α-methylbenzeneethanamine,

N-cyclohexyl-α-methyl-1-naphthalenemethanamine,

3-methoxy-α-methyl-N-(2-phenylcyclohexyl)benzoylmethylene,

3-methoxy-α-methyl-N-(3-phenylcyclohexyl)benzoylmethylene,

3-labels and-α-methyl-N-(4-phenylcyclohexyl)benzoylmethylene,

4-chloro-N-cyclohexyl-α-methylbenzeneethanamine,

N-(1-phenylethyl)cycloheptanone,

or its pharmaceutically acceptable salt, MES or in vivohydrolyzable ether complex.

In another aspect this invention relates to the compound of formula I, which is described here for use as drug therapy.

In another aspect this invention relates to the compound of formula I, which is described here, or such a connection, as

N-cyclopentyl-α-methylbenzeneethanamine,

N-cyclohexyl-α-methylbenzeneethanamine,

3-[3-[(1-phenylethyl)amino]cyclohexyl]phenol,

2-[3-[3-[(1-phenylethyl)amino]cyclohexyl]phenoxy], ethyl ester, acetic acid,

N-[3-(3-methoxyphenyl)cyclohexyl]-α-methyl-2-naphthalenemethanamine,

N-[3-(3-methoxyphenyl)cyclohexyl]-α-methylbenzeneethanamine,

N-cyclohexyl-α-methyl-1-naphthalenemethanamine,

4-chloro-N-cyclohexyl-α-methylbenzeneethanamine or

N-(1-phenylethyl)cycloheptanone,

for use in the treatment, alleviation or prophylaxis of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism.

In an additional aspect, the invention relates to the use of compounds of General formula I, which is described here, or such compounds as

N-cyclopentyl-α-methylbenzeneethanamine,

N-C is clohessy-α-methylbenzeneethanamine,

3-[3-[(1-phenylethyl)amino]cyclohexyl]phenol,

2-[3-[3-[(1-phenylethyl)amino]cyclohexyl]phenoxy], ethyl ester, acetic acid,

N-[3-(3-methoxyphenyl)cyclohexyl]-α-methyl-2-naphthalenemethanamine,

N-[3-(3-methoxyphenyl)cyclohexyl]-α-methylbenzeneethanamine,

N-cyclohexyl-α-methyl-1-naphthalenemethanamine,

4-chloro-N-cyclohexyl-α-methylbenzeneethanamine or

N-(1-phenylethyl)cycloheptanone,

for the manufacture of a medicinal product for the prevention, cure or relief of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism.

In another aspect the invention relates to pharmaceutical compositions containing a compound of the formula I, which is described herein, or its pharmaceutically acceptable salt, MES or hydrolyzablein vivoester together with a pharmaceutically acceptable excipient or the media.

In another aspect the invention relates to a method for prevention, treatment and relief of carcinoma of the parathyroid gland, adenoma of the parathyroid gland, the primary hyperplasia of the parathyroid gland, heart, kidney or intestinal dysfunctions, diseases of the Central nervous system, chronic renal failure, chronic kidney disease, primary hyperparathyroidism, secondary hyperparathyroidism, reticulo hyperparathyroidism, anemia, cardiovascular diseases, fibrotic generalized Ostia, adinamicheskoy disease of bone, osteoporosis caused by steroid osteoporosis, senile osteoporosis, post-menopausal osteoporosis, osteomalacia and related bone disorders, bone loss after kidney transplantation, gastrointestinal diseases, endocrine and neurodegenerative diseases, cancer, Alzheimer's disease, hypercalcemia or bone disease associated with renal disease, comprising administration to a patient in need, an effective amount of compounds of General formula I, which is described herein, optionally in combination or with addition of active Sterol of vitamin D or a vitamin derivative-D, such as 1-α-hydroxycholecalciferol, ergocalciferol, cholecalciferol, 25-hydroxycholecalciferol, 1-α-25-dihydroxycholecalciferol, or in combination or with the addition of phosphate binders, estrogens, calcitonin or bifosfonatami.

DETAILED description of the INVENTION

Definitions

The term "cycloalkyl" is intended to indicate a saturated cycloalkane radical containing 3-8 carbon atoms, for example 4-7 or 3-6 carbon atoms, for example 4-6 or preferably 5-6 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cyclo is heptyl.

The termis intended to indicate a saturated cycloalkane radical containing 4-7 carbon atoms, for example, 4-6 or 5-6 carbon atoms, preferably 5 carbon atoms or 6 carbon atoms, such as cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.

The term "cycloalkenyl" is intended to indicate mono - or di-unsaturated non-aromatic cyclic hydrocarbon radical containing 3-8 carbon atoms, for example, 4-7, for example, 3-6 carbon atoms, for example, 4-6 or preferably 5-6 carbon atoms, such as cyclobutenyl, cyclopentenyl or cyclohexenyl.

The term "heteroseksualci" is intended to cover cycloalkyl radical, as defined above, containing 1-7 carbon atoms, for example, 1 to 6 carbon atoms, in particular 4-, 5 - or 6-membered ring containing 2-5 carbon atoms and 1-5 heteroatoms (selected from O, S and N), for example, 3-5 carbon atoms and 1-3 heteroatoms, preferably 4-5 carbon atoms and 1-2 heteroatoms selected from O, S or N, such as morpholino, morpholinyl, pyrrolidinyl, oxopyrrolidin, piperidino, azetidine, tetrahydrofuran, tetrahydropyranyl, oxitetracycline, oxoacridine, oxetanyl, dioxoimidazolidin, piperidyl or piperazinil.

The term "geteroseksualen" is intended for the transport is achene cycloalkenyl radical, defined above, containing 1-7 carbon atoms, for example, 1 to 6 carbon atoms, in particular 5 - or 6-membered ring containing 1-5 carbon atoms and 1-5 heteroatoms (selected from O, Sand (N), for example, 3-5 carbon atoms and 1-3 heteroatoms, preferably 4-5 carbon atoms and 1-2 heteroatoms selected from O, S or N.

The term "heterocyclizations" is intended to encompass radical of the formula-OR, where R is heteroseksualci identified above, for example, oxopiperidine.

The term "heterocollateral" is intended to cover radicals geteroseksualbnogo rings (rings), in particular 5 - or 6-membered ring containing 1-5 carbon atoms and 1-4 heteroatoms selected from O, N or S, for example, from 1 to 5 carbon atoms and 1-3 heteroatoms, preferably 2-5 carbon atoms and 1-2 heteroatoms, and geteroseksualnoe ring condensed or annulirovano with one or more aromatic carbocyclic rings containing 6 to 10 carbon atoms, such as phenyl or naphthyl.

The term "aryl" is intended to denote the radical of an aromatic carbocyclic ring (rings)containing 6-20 carbon atoms, for example 6-14 carbon atoms, preferably 6-10 carbon atoms, in particular 6-membered ring, optionally condensed or annelated carbocyclic to the LEC at least one aromatic ring, such as phenyl, naphthyl, 1-naphthyl or indanyl.

The term "heteroaryl" is intended to denote radicals of heterocyclic aromatic rings (rings, containing 1-4 heteroatoms (selected from O, S and N) and 1-10 carbon atoms, for example 1-3 heteroatoms and 1-6 carbon atoms, for example 1-3 heteroatoms and 2 to 5 carbon atoms, for example 1-2 heteroatoms and 3-5 carbon atoms, preferably 5 - or 6-membered rings with 1-3 heteroatoms selected from O, S and N, and 2-5 carbon atoms or 1 to 3 heteroatoms and 2 to 4 carbon atoms, such as pyridyl, thiazolyl, imidazolyl, isoxazole, [l,2,4]oxadiazolyl, oxazolyl, pyrazolyl, indolyl, thienyl, furyl, 1-benzo[b]thiophenyl, 2,3-dihydrobenzo[1,4]dioxines or 2,3-dihydrobenzofuran.

The term "halogen" is intended to denote a Deputy from the 7th main group of the periodic system of elements, preferably it is fluorine, chlorine, iodine or bromine.

In this context, the term "alkyl" is intended to denote a radical formed when one hydrogen atom is removed from a hydrocarbon. The specified alkyl contains 1 to 6, preferably 1-4, or 1-3, for example 2-4 or 1-2 carbon atoms. The term includes the subclasses of normal alkyl (n-alkyl), secondary and tertiary alkyl, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, hexyl or isohexyl.

The term "alkenyl" is intended to indicate mono-, di - or tri-unsaturated hydrocarbon radical containing 2-6 carbon atoms, in particular 2-4 carbon atoms, for example 2-3 carbon atoms, such as vinyl, allyl, propenyl, butenyl, pentenyl or hexenyl.

The term "quinil" is intended to denote a hydrocarbon radical containing 1-4 triple bond C-C, for example, 1, 2 or 3 triple bond and 2 to 6 carbon atoms, alanovoy chain, usually containing 2-5 carbon atoms, in particular 2-4 carbon atoms, for example 2-3 carbon atoms, such as ethinyl, PROPYNYL, butynyl or pentenyl.

The term "hydroxyalkyl" is intended to indicate an alkyl radical, as defined above, where one, two, three or more hydrogen atoms substituted by hydroxy, such as hydroxymethyl, hydroxyethyl, hydroxypropyl, hydroxybutyl etc.

The term "halogenated" is intended to indicate an alkyl radical, as defined above, where one, two, three or more hydrogen atoms replaced by halogen, the same or different, such as iodine, chlorine, bromine and/or fluorine, such as foradil, defloratin, deformity or trifluoromethyl.

The term "aminoalkyl" is intended to indicate an alkyl radical, as defined above in which one or two hydrogen atoms replaced by-NH2such as aminomethyl, the amine is ethyl or aminopropyl.

The term "aminocarbonyl" is intended to indicate a radical of the formula-C(O)-NRR'where R and R' independently represent hydrogen, alkyl, cycloalkyl or alkenyl listed above, such as aminocarbonyl, methylaminomethyl, ethylaminomethyl, propylaminoethyl, tert-butylaminoethyl, cyclopropanecarbonyl, isopropylaminocarbonyl, second-butylaminoethyl, methylaminomethyl, dimethylaminoethyl or diethylaminoethyl.

The term "alkylaryl" is intended to indicate a radical of the formula-C(O)-R, where R is alkyl, listed above, such as methylcarbamoyl, ethylcarboxyl.

The term "alkoxy" is intended to indicate a radical of the formula-OR, where R is alkyl or alkenyl listed above, such as methoxy, ethoxy, n-propoxy, isopropoxy, butoxy, tert-butoxy etc.

The term "alkoxyalkyl" is intended to indicate a radical of the formula-OR-OR where R is alkyl or alkenyl listed above, such as methoxyethoxy, ethoxyethoxy, ethoxyethoxy, ethoxyethoxy etc.

The term "alkoxycarbonyl" is intended to indicate a radical of the formula-C(O)-O-R, where R is alkyl, listed above, such as methoxycarbonyl, etoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, tert-butoxycarbonyl etc.

The term "alkali is bonelace" is intended to indicate a radical of the formula-O-C(O)-R, where R represents alkyl, listed above, such as methylcarbonate or ethylcarbonate.

The term "alkoxycarbonyl" is intended to indicate a radical of the formula-C(O)NR'-O-R, where R' represents hydrogen or alkyl, which is defined above, and R represents alkyl, listed above, such as methoxycarbonyl, tert-butoxycarbonyl.

The term "amino" is intended to indicate a radical of the formula-NRR', where R and R' independently represent hydrogen, alkyl or alkenyl listed above, such as-NH2methylamino, ethylamino, propylamino, dimethylamino, diethylamino, isopropylamino, sec-butylamino, tert-butylamino or ethylmethylamino.

The term "cycloalkenyl" is intended to indicate a radical of the formula-NRR', where R represents hydrogen or alkyl and R' represents cycloalkyl listed above, such as cyclopropylamino.

The term "arylamino" is intended to indicate a radical of the formula-NRR', where R represents hydrogen or alkyl, which is defined above, and R' is aryl, which is specified above, such as phenylamino or indanamine.

The term "alkoxyaryl" is intended to indicate a radical of the formula-Ar-O-R, where Ar represents aryl, which is defined above, and R represents alkyl, listed above, such as methoxyphenyl or ethoxyphenyl.

The term "carboxyethyl" p is adnanced to denote a radical of the formula Ar-C(O)OH, where Ar represents aryl, which is specified above, such as carboxyvinyl.

The term "heteroarenes" is intended to indicate a radical of the formula-NRR', where R represents hydrogen or alkyl, which is defined above, and R' represents heteroaryl listed above.

The term "geterotsiklicheskikh" is intended to indicate a radical of the formula-C(O)-R, where R is heteroseksualci listed above, such as piperidinylcarbonyl, morpholinoethyl, morpholinylcarbonyl, piperazinylcarbonyl, pyrrolidinylcarbonyl, oxopyrrolidin, piperidinylcarbonyl or azetidinone.

The term "aminocarbonyl" is intended to indicate a radical of the formula-C(O)-NR'2where each R' independently represents hydrogen, alkyl, alkenyl or cycloalkyl listed above, such as carbarnoyl, methylaminomethyl, ethylaminomethyl, dimethylaminoethyl, diethylaminoethyl, ethylmethylamino, methylaminomethyl, propylaminoethyl, isopropylaminocarbonyl, butylaminoethyl, second-butylaminoethyl, tert-butylaminoethyl, cyclopropanecarbonyl or cyclohexylcarbonyl.

The term "hydroxyaminobuteroyl" is intended to indicate a radical of the formula-C(O)-NR'-OH, where R' independently represents hydrogen or alkyl, which is specified above.

The term "aryl is enacarbil" is intended to indicate a radical of the formula-C(O)-NR'-aryl, where R' independently represents hydrogen or alkyl, which is defined above and aryl is the same as described above, such as phenylenecarbonyl, indanylaminopropane.

The term "heteroarylboronic" is intended to indicate a radical of the formula-C(O)-NR'-heteroaryl, where R' independently represents hydrogen or alkyl, which is specified above, and heteroaryl is such as described above, such as personalmanagement, pyridineboronic.

The term "cycloalkylcarbonyl" is intended to indicate a radical of the formula-C(O)-NR'-cycloalkyl, where R' independently represents hydrogen or alkyl, which is specified above, and cycloalkyl is such as described above, such as cyclopropanecarbonyl, cyclobutanecarbonyl, cyclopentanecarbonyl or cyclohexylcarbonyl.

The term "heterocyclizations" is intended to indicate a radical of the formula-C(O)-NR'-heteroseksualci, where R' independently represents hydrogen or alkyl, which is specified above, and heteroseksualci is such as described above, such as tetrahydropyrimidines or externalinternal.

The term "alkylsulfonamides" is intended to indicate a radical of the formula-C(O)-NR'-S(O)2-R, where R' independently represents hydrogen, alkyl or cycloalkyl described above, the R represents alkyl, listed above, such as methylsulfonylmethane.

The term "aryloxy" is intended to indicate a radical of the formula-O-R, where R is aryl, which is specified above, such as phenyloxy.

The term "aryloxyalkyl" is intended to indicate a radical of the formula-C(O)-O-R, where R is aryl, which is specified above, such as vinyloxycarbonyl.

The term "heteroaromatic" is intended to indicate a radical of the formula-O-R, where R is heteroaryl listed above.

The term "heteroarylboronic" is intended to indicate a radical of the formula-C(O)-O-R, where R is heteroaryl listed above.

The term "alkylthio" is intended to indicate a radical of the formula-S-R, where R is alkyl, which is specified above.

The term "iminomethyl" is intended to indicate a radical-CH=NH.

The term "gidroksilaminami" is intended to indicate a radical-CH=N-(OH).

The term "aminosulfonyl" is intended to indicate a radical of the formula-S(O)2-NR2where each R independently represents hydrogen or alkyl, listed above, such as ethylaminomethyl.

The term "alkylsulfonyl" is intended to indicate a radical of the formula-S(O)2-R, where R is alkyl, which is specified above.

The term "arylsulfonyl" prednaznachet is to indicate a radical of the formula-S(O) 2-R, where R is aryl, which is specified above, such as phenylsulfonyl.

The term "heterocyclisation" is intended to indicate a radical of the formula-S(O)2-R, where R is heteroseksualci listed above, such as morpholinomethyl.

The term "aminocarbonyl" is intended to indicate a radical of the formula-O-C(O)-NRR'where R and R' independently represent hydrogen or alkyl, which is specified above.

The term "alkylcarboxylic" is intended to indicate a radical of the formula-NR'-C(O)-R, where R' represents hydrogen or alkyl, which is defined above, and R represents alkyl, listed above, such as methylcobalamine.

The term "alkoxycarbonyl" is intended to indicate a radical of the formula-NR'-C(O)-O-R, where R' represents hydrogen or alkyl, which is defined above, and R represents alkyl, which is specified above.

The term "alkylsulfonyl" is intended to indicate a radical of the formula-NR'-S(O)2-R, where R is alkyl, which is defined above, and R' represents hydrogen or alkyl, listed above, such as methylsulfonylamino, ethylsulfonyl, propylsulfonyl or butylsulfonyl.

The term "arylsulfonyl" is intended to indicate a radical of the formula-NR'-S(O)2-R, where R is aryl, which is defined above and R' represent the screens hydrogen or alkyl, listed above, such as phenylcarbonylamino.

The term "alkoxycarbonyl" is intended to indicate a radical of the formula-O-S(O)2-O-R, where R is alkyl, which is specified above.

The term "arylsulfonamides" is intended to indicate a radical of the formula-C(O)-NR'-S(O)2-R, where R is aryl, which is defined above, and R' represents hydrogen or alkyl, listed above, such as vinylsulfonylacetamido.

The term "arylcarboxamide" is intended to indicate a radical of the formula-NR'-C(O)-R, where R' represents hydrogen or alkyl, which is defined above, and R represents aryl, which is specified above, such as phenylcarbonylamino.

The term "alkenylboronic" is intended to indicate a radical of the formula-NR'-C(O)-R, where R' represents hydrogen or alkyl, which is defined above, and R represents alkenyl listed above.

The term "cycloalkylcarbonyl" is intended to indicate a radical of the formula-NR'-C(O)-R, where R' represents hydrogen or alkyl, which is defined above, and R represents cycloalkyl listed above.

The term "cycloalkylcarbonyl" is intended to indicate a radical of the formula-NR'-C(O)-R, where R' represents hydrogen or alkyl, which is defined above, and R represents cycloalkenyl listed above.

The term "heterocyclyl is ylcarbonyl" is intended to indicate a radical of the formula-NR'-C(O)-R, where R' represents hydrogen or alkyl, which is defined above, and R represents heteroseksualci listed above.

The term "ureido" is intended to indicate a radical of the formula-NR'-C(O)-NH-R, where R' represents hydrogen or alkyl, which is defined above, and R represents hydrogen, alkyl, alkenyl, quinil, cycloalkyl or aryl, above.

The term "touraid" is intended to indicate a radical of the formula-NR'-C(S)-NH-R, where R' represents hydrogen or alkyl, which is defined above, and R represents hydrogen, alkyl or cycloalkyl listed above.

The term "pharmaceutically acceptable salt" is intended to indicate salts obtained by reaction of compounds of formula I with the appropriate inorganic or organic acid, such as hydrochloric, Hydrobromic, uudistoodetena, sulphuric, nitric, phosphoric, formic, acetic, 2,2-dichloracetic, Kalinova, adipic, ascorbic, L-aspartic, L-glutamic, galactosemia, lactic, maleic, L-malic, phthalic, citric, propionic, benzoic, glutaric, gluconic, D-glucuronic methansulfonate, salicylic, succinic, malonic, tartaric, benzolsulfonat, ethane-1,2-disulfonate, 2-hydroxyethanesulfonic acid, toluensulfonate, sulfamic or fumaric acid. Pharmaceutically reception is going salts of the compounds of formula I can also be obtained by reaction with an appropriate base, such as sodium hydroxide, potassium hydroxide, magnesium hydroxide, calcium hydroxide, ammonia or suitable non-toxic amines, such as lower alkylamines followed, for example triethylamine, hydroxy-lower alkylamines followed, for example 2-hydroxyethylamine, bis-(2-hydroxyethyl)amine, cyclooctylamine, such as dicyclohexylamine, or benzylamines, for example N,N'-dibenzylidene-diamine and dibenzylamine, or L-arginine or L-lysine.

The term "MES" is intended to denote compounds formed during the interaction of compounds, for example, the compounds of formula I and a solvent such as alcohol, glycerine or water, where these compounds are in solid form. When water is the solvent, these compounds are referred to as a hydrate.

The term "pharmaceutically acceptable hydrolyzablein vivoester" is intended to refer to easily hydrolyzablein vivoesters, i.e. hydrolyzablein vivoesters of compounds of formula I, such as alkanoyloxy, arachnodactyly, urologically, for example, acetoxymethyl, pivaloyloxymethyl, benzoyloxymethyl esters and the corresponding 1'-oxyethylated derivatives or alkoxycarbonylmethyl esters, for example, methoxycarbonylmethyl esters and ethoxycarbonylmethylene complex is Firov and the corresponding 1'-oxyethylated derivatives, or victoriavi esters, for example, palidrome esters, or dialkylaminoalkyl esters, for example, dimethylaminoethyl esters. Such esters can be obtained by conventional methods known to experts in this field, such as the method disclosed in UK patent No. 1490852 included in this description by reference.

The compounds of formula I may contain asymmetrically substituted (chiral) carbon atoms and carbon-carbon double bond, which can ensure the existence of isomeric forms such as enantiomers, diastereomers and geometric isomers. The invention includes all such isomers, or in pure form or as mixtures thereof. Pure stereoisomeric forms of the compounds and intermediates in this invention can be obtained by procedures known in the art. The diastereomers can be separated by physical separation methods such as selective crystallization and chromatographic techniques, e.g. liquid chromatography using chiral stationary phases. Enantiomers can be separated from each other by the selective crystallization of their diastereomeric salts with optically active acids. Alternatively, the enantiomers can be separated by chromatographic methods is AMI using chiral stationary phases. These pure stereoisomeric forms may also be derived from the corresponding pure stereoisomeric forms of the appropriate starting materials, provided that the reaction proceeds stereoselective or stereospecific. Preferably, if desired specific stereoisomer, to synthesize the specified connection stereoselective or stereospecific methods of getting. These methods include the predominant use of pure chiral starting materials. Similarly, pure geometric isomers can be obtained from the corresponding pure geometric isomers of the corresponding starting materials. A mixture of geometric isomers will typically exhibit different physical properties, and therefore they can be separated by standard chromatographic methods well known in the art.

The invention additionally relates to prodrugs of compounds of General formula I, such as esters, ethers, complexes or other derivatives that are subject to biotransformation in vivobefore the onset of their pharmacological effects.

The compounds of formula I can be obtained in crystalline form either directly by concentration of the organic solvent or by crystallization or recrystallization of the institutions the institutions solvent or a mixture of the solvent and jointly acting solvent, which can be organic or inorganic, such as water. Crystals can be isolated in the form of an essentially solvent free, or as MES, such as a hydrate. The invention covers all crystal modifications and forms, and mixtures thereof.

Options exercise

In one embodiment, the present invention compound I is:

In one embodiment of the present invention groupis:

In another embodiment of this invention R2and R3represent hydrogen.

In another embodiment, the present invention represents A 1-naphthyl.

In another embodiment of this invention G is-C(O)R6where R6represents-NH2C1-6amino, hydroxy, mercapto, -C(O)NH2, trifluoromethyl, carboxy, C1-6alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4aminocarbonyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6geteroseksualen, C3-6cyclooctylamino, C1-6heteroseksualci, C1-6geterotsiklicheskikh, C6-14aryl, C1-6heteroaryl, C6-10Ari is amino, carboxy C6-10aryl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4aminocarboxylate, C1-4alkylsulfonyl, C1-4alkylcarboxylic, C1-4alkenylamine, C3-6cycloalkylcarbonyl, C3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl, C6-10arylcarboxamide or C6-10arylsulfonamides,

where specified C1-6amino, C1-6alkyl, C2-4alkenyl, C2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4aminocarbonyl, C3-6cycloalkyl, C3-6cycloalkenyl, C1-6geteroseksualen, C3-6cyclooctylamino, C1-6heteroseksualci, C1-6geterotsiklicheskikh, C6-14aryl, C1-6heteroaryl, C6-10arylamino, carboxy6-10aryl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkylthio, C1-4aminocarboxylate, C1-4alkylsulfonyl, C1-4alkylcarboxylic, C1-4alkenylamine, C3-6cycloalkylcarbonyl, C3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl, C6-10arylcarboxamide or C6-10arylsulfonamides may be additionally required is certainly substituted by one or more identical or different substituents, such as hydroxy, halogen, C1-4alkyl, C1-3alkoxy, C1-4alkoxycarbonyl, C1-6heteroseksualci, C6-12aryl or oxo,

where specified C1-4alkyl, C1-3alkoxy, C1-4alkoxycarbonyl, C1-6heteroseksualci or C6-12aryl are optionally additionally substituted by trifluoromethyl, halogen, C1-4the alkyl, C1-3alkoxy or C1-4alkoxycarbonyl.

In another embodiment of this invention G is-C(O)NH2With1-4aminocarbonyl, C4-5geterotsiklicheskikh, C6-10allumination, C6-10arylsulfonamides,

where specified1-4aminocarbonyl, C4-5geterotsiklicheskikh, C6-10allumination, C6-10arylsulfonamides are optionally substituted by one or more, same or different substituents selected from oxo, hydroxy, C1-4of alkyl, C1-3alkoxy, C1-3alkoxycarbonyl, C4-5geterotsiklicheskie, C6-10aryl,

where specified1-4alkyl, C1-3alkoxy, C1-3alkoxycarbonyl, C4-5heteroseksualci or C6-10aryl are optionally substituted by one or more identical or different substituents, such as halogen, trifluoromethyl, C1-3alkoxy or1-3alkoxycarbonyl.

In another embodiment of this invention G is methylpiperazine, cyclopropanecarbonyl, isopropylaminocarbonyl, propylaminoethyl, morpholinoethyl, dimethylaminoethyl, isobutylparaben, ethylaminomethyl, N-methoxy-N-methylaminomethyl, methoxycarbonylaminophenyl, methoxyethylamine, ethoxycarbonylpyrimidine, dimethyldithiocarbamic, morpholinepropanesulfonic, ethoxycarbonylpyrimidine, chlorobenzenesulfonyl, phenylhydroxylamine, ethoxycarbonylmethylene, triftormetilfullerenov, hydroxyindoleacetic, phenylmethanesulfonyl, methoxyacetophenone, triptoreline, methoxycarbonylaminophenyl, methylphenylethylamine or carboxymethylaminomethyl.

In another embodiment of this invention G is phenyl, optionally substituted by one or more, same or different substituents selected from such as-C(O)H, -C(O)NH2, hydroxy, halogen, cyano, nitro, amidino, carboxy, trifluoromethyl, C1-6alkyl, C2-4alkenyl, C2-4quinil,1-4hydroxyalkyl,1-6amino, amino1-3alkyl, iminomethyl, hydroxyine who said; " the, With1-6halogenated,1-4alkoxy, C1-4alkoxycarbonyl,1-3alkoxycarbonyl,1-4aminocarbonyl,1-3alkylsulfonamides, hydroxyaminobuteroyl,1-6heterocyclizations,1-6heterocyclizations, C3-6cycloalkylcarbonyl,6-10allumination,1-10heteroarylboronic, C3-6cycloalkyl,1-6heteroseksualci,1-6geteroseksualen,1-6geterotsiklicheskikh,1-4alkylcarboxylic,1-4alkoxycarbonyl,1-4alkoxycarbonyl,1-4alkylthio, C3-6cycloalkenyl,1-4aminosulfonyl,1-4aminocarboxylate,1-4alkylsulfonamides,1-10heteroaryl, C6-10arylamino, C6-10aryloxyalkyl, C6-10arylcarboxamide, C6-10arylsulfonamides,1-4alkylcarboxylic,1-4alkenylamine, C3-6cycloalkylcarbonyl, C3-6cycloalkylcarbonyl,1-4alkoxycarbonyl,1-6geterotsiklicheskikh,1-4alkylsulfonyl or1-4heterocyclisation,

where these C(O)NH2With1-6alkyl, C2-4alkenyl, C2-4quinil,1-4hydroxyalkyl,1-6amino, amino1-3alkyl, iminomethyl, gidroksilaminami,1-6ha is hogenakkal, With1-4alkoxy, C1-4alkoxycarbonyl,1-3alkoxycarbonyl,1-4aminocarbonyl,1-3alkylsulfonamides, hydroxyaminobuteroyl,1-6heterocyclizations,1-6heterocyclizations, C3-6cycloalkylcarbonyl,6-10allumination,1-10heteroarylboronic, C3-6cycloalkyl,1-6heteroseksualci,1-6geteroseksualen,1-6geterotsiklicheskikh,1-4alkylcarboxylic,With1-4alkoxycarbonyl,1-4alkoxycarbonyl,1-4alkylthio, C3-6cycloalkenyl,1-4aminosulfonyl,1-4aminocarboxylate,1-4alkylsulfonamides,1-10heteroaryl, C6-10arylamino, C6-10aryloxyalkyl, C6-10arylcarboxamide, C6-10arylsulfonamides,1-4alkylcarboxylic,1-4alkenylamine, C3-6cycloalkylcarbonyl, C3-6cycloalkylcarbonyl,1-4alkoxycarbonyl,1-6geterotsiklicheskikh,1-4alkylsulfonyl or1-4heterocyclisation

are optionally additionally substituted by one or more, same or different substituents selected from the group consisting of such substituents as hydroxy, -NH2With1-6Amin is, iminomethyl, gidroksilaminami, carboxy, trifluoromethyl, halogen, oxo, mercapto, cyano, -C(O)NH2, nitro, C1-6alkyl, C2-4alkenyl, C2-4quinil,1-4hydroxyalkyl,1-6halogenated,1-3alkoxy, C1-4alkoxycarbonyl,1-6geterotsiklicheskikh, C3-6cycloalkyl, C3-6cycloalkenyl,1-6heteroseksualci, C6-12aryl, C1-10heteroaryl,1-3alkoxyl6-10aryl, C1-10heterocollateral,1-6geteroseksualen, -S(O)2NH2, -S(O)2OH,1-6ureido,1-6toureiro,1-4alkylcarboxylic,1-4alkoxycarbonyl,1-4alkoxycarbonyl,1-4alkoxycarbonyl,1-4aminocarbonyl,1-4alkylthio,1-4aminosulfonyl,1-4aminocarboxylate,1-4alkylsulfonamides;C6-12arylsulfonyl, C6-10arylsulfonamides,1-4alkylcarboxylic or1-4alkylsulfonyl,

where specified C3-6cycloalkyl,1-6alkyl, C1-3alkoxy, C1-4alkoxycarbonyl,1-6heteroseksualci, C6-10aryl or1-10heteroaryl can be optionally substituted by carboxy, halogen, hydroxy, cyano, C1-6heterocyclization, one or more1-6alkilani,1-3alkoxy, C1-3alkoxyl1-31-4alkoxycarbonyl,1-3hydroxyalkyl or C6-10Allami.

In another embodiment of this invention G is phenyl, substituted by one or more identical or different substituents selected from such as cyano, carboxy, -C(O)H, -C(O)NH2, hydroxyl, halogen, amidino, iminomethyl, gidroksilaminami,1-6alkyl, C2-4quinil, aminos1-3alkyl, C1-3alkoxy, C1-3alkoxycarbonyl,1-4alkoxycarbonyl,1-3aminocarbonyl,3-6cycloalkyl,1-6heteroseksualci,1-6geterotsiklicheskikh,1-6heterocyclizations, C1-3aminocarboxylate,1-10heteroaryl, C6-10arylamino, C6-10aryloxyalkyl,1-3alkylsulfonamides, hydroxyaminobuteroyl,1-3alkylsulfonyl, C1-6heterocyclisation,1-6heterocyclizations, C3-6cycloalkylcarbonyl,6-10allumination,1-3aminosulfonyl,1-10heteroarylboronic,1-3alkylcarboxylic,1-3alkylsulfonate or6-10arylsulfonamides,

each of which is optionally substituted by one or more identical or different substituents selected from such groups as hydroxy, -NH2With1-3and the Ino, aminomethyl, carboxy, trifluoromethyl, cyano, fluorine, chlorine, iodine, oxo, mercapto, C1-4alkyl, C1-3hydroxyalkyl,1-2alkoxy, C1-4alkoxycarbonyl, C3-6cycloalkyl, C3-6heteroseksualci,1-6geterotsiklicheskikh,6-10aryl, C1-10heteroaryl,1-2alkoxyl6-10aryl, C1-3alkylsulfonyl, -S(O)2OH or1-3alkylcarboxylic,

where specified C3-6cycloalkyl,1-4alkyl, C1-2alkoxy, C1-4alkoxycarbonyl,1-6heteroseksualci, C6-10aryl or1-10heteroaryl are optionally additionally substituted carboxy, halogen, hydroxy, cyano, C1-6heterocyclization, one or more1-6alkilani,1-3alkoxy, C1-3alkoxyl1-3alkoxy, C1-4alkoxycarbonyl,1-3hydroxyalkyl or C6-10Allami, such as hydroxyethylpyrrolidine, ethylaminomethyl, dimethylaminoethylmethacrylate, pyrrolidinedione, amidino, aminohydrocinnamic, methoxycarbonyl, etoxycarbonyl, hydroxyethylaminomethyl, N-hydroxyethyl-N-methylaminomethyl, N-hydroxymethyl-N-propylaminoethyl, bishydroxycoumarin, dihydroxy-tert-butylaminoethyl, N-hydroxyethyl-N-ethylaminomethyl, cyanoethylation, morpholinoethyl aminocarbonyl, teretiarikare, differentillumination, methoxycarbonylaminophenyl, N-pyridylmethyl-N-methylaminomethyl, benzyloxycarbonyl, methylcarbamoylmethyl, iodinedeeciency, methoxyethylmercury, mercaptoethylamine, ethoxycarbonylmethylene, sulfoaluminate, dimethylaminoethyl, diethylaminoethylamine, dimethylaminopropylamine, piperidinylcarbonyl, methylpiperazine, hydroxyethylpiperazine, morpholinoethyl, hydroxypiperidine, imidazolidinylideneamino, carboxymethylaminomethyl,tert-bethoxycarbonylmethylene,tert-bbutoxycarbonyloxyimino, methoxycarbonylaminophenyl, carboxymethylaminomethyl, methoxycarbonylaminophenyl, carboxypolymethylene, N-ethoxycarbonylmethyl-N-cyclohexyloxycarbonyl, diethoxycarbonylcyclohexaneoxime,tert-bbutoxycarbonyloxyimino, carboxymethylaminomethyl, carboxymethylaminomethyl, methoxyisobutylisonitrile, N,N-diterbakicinternational, carboxyethylgermanium, carboxymethylaminomethyl, carboxymethylaminomethyl, ethylcarboxylate is of IMT, carboxylcontaining, carboxymethylaminomethyl, carboxybenzeneboronic, N-methyl-N-carboxymethylaminomethyl, carboxypropylbetaine, ethoxycarbonylpyrimidine, carboxypeptidases, N-carboxymethyl-N-cyclohexyloxycarbonyl, externalinternal, cyanomethaemoglobin, cyanodithioiminocarbonate, phenylmethanesulfonyl, methoxycarbonylaminophenyl, ethoxycarbonylpyrimidine, carboxyhydroxymethyl, carboxyhydroxymethyl, tert-butoxycarbonyl, methoxyaminomethyl, tetrahydroquinoxaline, N-methoxy-N-methylaminomethyl, phenylmethanesulfonyl, hydroxyaminobuteroyl, morpholinobenzenediazonium, methylsulfonylmethane, methoxycarbonylpropionyl, carboxyhydroxymethyl, ethoxycarbonylmethoxy, methoxycarbonylethyl, carboxymethoxy or carboxyethyl.

In one embodiment, when G represents phenyl which is optionally substituted, Deputy attached to the phenylene ring in the meta or paraprotein in relation to the place of attachment of the phenyl ring to cycloalkyl represented by the formula.

In another variationbetween, when G represents phenyl which is optionally substituted, Deputy attached to the phenylene ring in anthopology towards the place where the phenyl ring attached to cycloalkyl represented by the formula.

In another embodiment of this invention G is C1-10heteroaryl or1-6heteroseksualci, and where specified With1-10heteroaryl or1-6heteroseksualci is optionally substituted carboxy, C1-6the alkyl, C6-10the aryl, C1-3alkoxycarbonyl, which can be further optionally substituted by trifluoromethyl, halogen, C1-3the alkyl, C1-3alkoxy, C1-10heteroaryl, where C1-10heteroaryl may optionally be substituted With1-3the alkyl or oxo, such as tortenelem[1,2,4]oxadiazolyl, phenyl[1,2,4]oxadiazolyl, isopropyl[1,2,4]oxadiazolyl, triptoreline[1,2,4]oxadiazolyl, methyl[1,2,4]oxadiazolyl, methylthiazolidine[1,2,4]oxadiazolyl, propyl[1,2,4]oxadiazolyl, oxopyridine[1,2,4]oxadiazolyl, methoxyphenyl[1,2,4]oxadiazolyl, methylcarbamoylmethyl, ethoxycarbonylmethyl, ethoxycarbonylphenyl, pyridyl, carboxymethyl or carboxyphenyl.

In another embodiment of this invention G is phenylamino or phenyloxy, it is certainly substituted by cyano, carboxy, C1-4alkoxycarbonyl or trifluoromethyl.

In yet another embodiment of the present invention A represents 1-naphthyl, 2-naphthyl or phenyl, each of which is optionally substituted as indicated above for the substitution of C6-14aryl, representing A.

In another embodiment of this invention R4represents hydrogen, hydroxy, halogen or1-6alkyl.

In another embodiment of this invention R5represents hydrogen or C1-6alkyl.

In another embodiment of this invention R2, R3, R4and R5represent hydrogen.

In another embodiment of this invention R1represents methyl, ethyl or n-propyl, optionally substituted with halogen or hydroxy, such as methyl.

In another embodiment, this invention relates to compounds of General formula I, where G represents C6-10aryl, C1-3aminocarbonyl6-10aryl or1-4alkyls6-10aryl, optionally substituted carboxy, C1-3alkoxy or1-3alkoxycarbonyl, A represents 1-naphthyl, R2, R3, R4and R5represent hydrogen and R1represents methyl.

Specific examples of compounds of formula I may be selected from the group sotoyama which of the following compounds:

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (compound 1000),

cyclobutyl-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1001),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, dimethylamide (compound 1002),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid amide (compound 1003),

(4-methylpiperazin-1-yl)[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano, hydrochloride (compound 1004),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, cyclopropylamine (compound 1005),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, Isopropylamine (compound 1006),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, propylamide (compound 1007),

morpholine-4-yl-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1008),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, tert-butylamide (compound 1009),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, ethylamide (compound 1010),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid methoxy-methyl-amide, hydrochloride (compound 1011),

[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)cyclobutyl]((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1012),

((R)-1-naphthalene-1-retil){3-[3-(3-triptoreline)[1,2,4]oxadiazol-5-yl]cyclobutyl}amine, hydrochloride (compound 1013),

[3-(3-IU the Il[1,2,4]oxadiazol-5-yl)cyclobutyl]((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1014),

((R)-1-naphthalene-1-retil)[3-(3-phenyl[1,2,4]oxadiazol-5-yl)cyclobutyl]amine, hydrochloride (compound 1015),

((R)-1-naphthalene-1-retil){3-[3-(4-triptoreline)[1,2,4]oxadiazol-5-yl]cyclobutyl}amine, hydrochloride (compound 1016),

{3-[3-(4-methoxyphenyl)[1,2,4]oxadiazol-5-yl]cyclobutyl)-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1017),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, 4-Chlorobenzilate (compound 1018),

{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}acetic acid, methyl ester (compound 1019),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (2-methoxyethyl)amide (compound 1020),

4-{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}benzoic acid, ethyl ester (compound 1021),

(2,6-dimethylmorpholine-4-yl)[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1022),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (3-morpholine-4-ylpropyl)amide (compound 1023),

1-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]piperidine-4-carboxylic acid, ethyl ester (compound 1024),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (2-hydroxy-2-phenylethyl)amide (compound 1025),

3-{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}propionic acid, ethyl complex EPE is (compound 1026),

[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl][4-(3-triptoreline)piperazine-1-yl]metano (compound 1027),

{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid, methyl ester (compound 1028),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (2-hydroxyine-1-yl)amide (compound 1029),

[4-(2-methoxyethyl)piperazine-1-yl][3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1030),

3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, 2,3,6-triptoreline (compound 1031),

3-({[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}methyl)benzoic acid, methyl ester (compound 1032),

4-({[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}methyl)benzoic acid, methyl ester (compound 1033),

{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid (compound 1034),

((R)-1-naphthalene-1-retil)(3-phenylcyclohexyl)amine (compound 1035 and 1036 connection),

{3-[3-(4-forfinal)[1,2,4]oxadiazol-5-yl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1037),

((R)-1-naphthalene-1-retil)-[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]amine, hydrochloride (compound 1038),

[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1039),

((R)-1-naphthalene-1-retil)-{3-[3-(4-trift methylphenyl)[1,2,4]oxadiazol-5-yl]cyclopentyl}amine, hydrochloride (compound 1040),

[3-(3-methyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1041),

{3-[3-(5-methylthiazole-2-ylmethyl)-[1,2,4]oxadiazol-5-yl]cyclopentyl}((R)-1-naphthalene-1-retil)amine (compound 1042),

((R)-1-naphthalene-1-retil)[3-(3-propyl[1,2,4]oxadiazol-5-yl)cyclopentyl]amine, hydrochloride (compound 1043a and 1043b),

1-{5-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]-[1,2,4]oxadiazol-3-ylmethyl}-1H-pyridine-2-it, hydrochloride (compound 1044),

{3-[3-(4-methoxyphenyl)[1,2,4]oxadiazol-5-yl]cyclopentyl}((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1045),

3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid amide (compound 1046),

4-methyl-N-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl]benzosulfimide (connection 1047a, the connection 1047b, the connection 1047c and connection 1047d),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (connection 1048/1049/1050),

N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1051),

N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1052),

N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1053a and connection 1053b),

{3-[4-(aminopyrrolidine-1-ylmethyl)phenyl]cyclohexyl}((R)-1-naphthalene-1-retil)amine (compound 1054),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (soedinenii),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1057),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1058, 1058a),

3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, ethyl ester (compound 1059),

N-(2-hydroxyethyl)-3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1060),

3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1061/1062),

((R)-1-naphthalene-1-retil)-(3(S)-phenylcyclohexyl)amine (compound 1063),

((R)-1-naphthalene-1-retil)-(3(R)-phenylcyclohexyl)amine (compound 1064),

N-((R)-1-naphthalene-1-retil)-N'-phenylcyclohexane-l,3-diamine (compound 1065),

N-((R)-1-naphthalene-1-retil)-N'-(3-triptoreline)cyclohexane-l,3-diamine (compound 1066),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexylamino]benzonitrile (connection 1067),

(3-morpholine-4-illlogical)((R)-1-naphthalene-1-retil)amine (compound 1068),

((R)-1-naphthalene-1-retil)-(3-pyridin-2-illlogical)amine (compound 1069/1070),

5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]thiophene-2-carboxylic acid, ethyl ester (compound 1071),

5-[3-((R)-1-naphthalene~1 ylethylamine)cyclohexyl]thiophene-2-carboxylic acid (compound 1072),

5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carbon is the first acid, ethyl ester (compound 1073),

5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carboxylic acid (compound 1074a, the connection 1074b and connection 1074c),

{3-[3-(4-forfinal)[1,2,4]oxadiazol-5-yl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1075),

((R)-1-naphthalene-1-retil){3-[3-(4-triptoreline)[1,2,4]oxadiazol-5-yl]cyclohexyl}amine (compound 1076),

((R)-1-naphthalene-1-retil)[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclohexyl]amine (compound 1077),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1078),

N-benzyloxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1079),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 4-itfinally ester (compound 1080),

2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}econsultancy acid (compound 1081),

N-((R)-1-hydroxymethylpropane)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1082),

N-((S)-1-hydroxymethylpropane)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1083),

N-(2-cyanoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1084),

N-(2-morpholine-4-retil)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1085),

N-(2-foradil)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1086),

N-(2,2-dottorati)-4-[3-((R)-1-naphthalene-1-ilat the laminitis)cyclohexyl]benzamide (connection 1087),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1088),

N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-pyridin-4-ylmethylene (connection 1089),

N-(2-dimethylaminoethyl)-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1090),

(2-hydroxyethylpyrrolidine-1-yl){4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1091),

N-(2-acetylamino)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1092),

N-ethyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1093),

N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1094),

N-(2-hydroxy-1-hydroxymethyl-1-methylethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1095),

N-(2-methoxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1096),

N-(2-mercaptoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1097),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}acetic acid ethyl ester (compound 1098),

N,N-dimethyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1099),

N-(2-hydroxyethyl)N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1100),

N-ethyl-N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-Ile is ylamino)cyclohexyl]benzamide (connection 1101),

N,N-bis-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1102),

N-(2-dimethylaminoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1103),

N-(3-dimethylaminopropyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1104),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}piperidine-1-ylmethanone (connection 1105),

(4-methylpiperazin-1-yl){4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1106),

[4-(2-hydroxyethyl)piperazine-1-yl]{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1107),

morpholine-4-yl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1108),

(4-hydroxypiperidine-1-yl){4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1109),

N-(3-imidazol-1-ylpropyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1110),

3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (compound 1111),

{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine)acetic acid (compound 1115),

(S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid, 4-tert-butyl ester, 1-methyl ester (compound 1116),

(S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid, 4-tert-butyl complex EF the R (connection 1117),

(R)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid, methyl ester (compound 1118),

(R)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid (compound 1119),

(S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid, methyl ester (compound 1120),

(S)-2-[4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid, hydrochloride (compound 1121),

(S)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1122),

(S)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1123),

(R)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1124),

(R)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1125),

(cyclohexyl-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid ethyl ester (compound 1126),

2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}malonic acid diethyl ester (compound 1127),

(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-on the Talin-1 ylethylamine)cyclohexyl]benzoylamine}propionic acid, tert-butyl ester (compound 1128),

5-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}nicotinic acid (compound 1129),

4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid (compound 1130),

4-methoxy-3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid, methyl ester, hydrochloride (compound 1131),

2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid, hydrochloride (compound 1132),

(carboxymethyl-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid, hydrochloride (compound 1133),

1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}methyl)cyclopentanecarbonyl acid (compound 1134),

1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopentanecarbonyl acid, hydrochloride (compound 1135),

3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid hydrochloride (compound 1136),

(1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclohexyl)acetic acid, hydrochloride (compound 1137),

1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopropanecarbonyl acid, ethyl ester (compound 1138),

1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohex the l]benzoylamine}cyclopropanecarbonyl acid (compound 1139),

1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}methyl)cyclopropanecarbonyl acid (compound 1140),

2-methyl-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1141),

1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}azetidin-3-carboxylic acid (compound 1142),

(methyl-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1143),

4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}butyric acid (compound 1144),

1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid, ethyl ester (compound 1145),

1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid (compound 1146),

(cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid ethyl ester (compound 1147),

(cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1148),

4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-((R)-2-oxitetraciclina-3-yl)benzamide (connection 1149),

N-cyanomethyl-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1150),

N-(4-cyano-1H-pyrazole-3-yl)-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1151),

(R)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid, benzyl ester (compound 1152),

(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid, benzyl ester (compound 1153),

(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1154),

(R)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1155),

(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid, ethyl ester, hydrochloride (compound 1156),

3-hydroxy-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid hydrochloride (compound 1157),

(R)-4-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}butyric acid (compound 1158),

N-tert-butoxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, formate (compound 1159),

N-tert-butoxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, formate (compound 1160),

N-methoxy~4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, formate (compound 1161),

N-methoxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide; formate (connected to the e 1162),

4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-(tetrahydrofuran-3-ylethoxy)benzamide (connection 1163),

4-[3-(R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-(tetrahydrofuran-3-ylethoxy)benzamide (connection 1164),

N-methoxy-N-methyl-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, isformat (connection 1165),

N-methoxy-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1166),

N-benzyloxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1167),

N-benzyloxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1168),

N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1169),

N-hydroxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1170),

N-(2-morpholine-4-yl-2-oksidoksi)-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1171),

N-(2-morpholine-4-yl-2-oksidoksi)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1172),

N-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}methanesulfonamide (connection 1173),

4R-hydroxy-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2S-carboxylic acid, methyl ester (compound 1174),

4R-hydroxy-1-{4-[(1S,3S)-3-(R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2S-carboxylic acid (compound 1175),

N-{4-[-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}methanesulfonamide, hydrochloride (compound 1176),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid ethyl ester (compound 1177/1178),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid ethyl ester (compound 1179/1180),

3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid methyl ester (compound 1181/1182/1183/1184),

{4-[3-(R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1185),

{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1186),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1187),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1188),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1189),

3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1190),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1191),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1192),

{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid ethyl ester (compound 1193/1194/1195/1196),

3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid is one ethyl ester (compound 1197/1198/1198/1200),

{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid, hydrochloride (compound 1201),

{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1202),

{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1203),

3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1204),

3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1205),

3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1206),

3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1207),

3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1208),

[3-(4-itfinal)cyclohexyl]((R)-1-naphthalene-1-retil)amine (compound 1209),

1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}pyrrolidin-2-on (compound 1210),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxazolidin-2-on (compound 1211),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}ndimethylacetamide (connection 1212),

4-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydropyran-4-ol (compound 1213),

[3-(4-imidazol-1-ylphenyl)cyclohexyl]((R)-1-naphthalene-1-retil)amine (compound 1214),

1-{4-[3-((R)-1-is aftalen-1 ylethylamine)cyclohexyl]phenyl}Cyclopentanol (connection 1215),

1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}Etalon (connection 1216),

4-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydropyran-4-ol, hydrochloride (compound 1217),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanol (compound 1218),

1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}cyclobutanol (connection 1219),

2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}malonic acid diethyl ester (compound 1220),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid ethyl ester (compound 1221),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid (compound 1222),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxetan-3-ol (compound 1223),

{3-[4-(3-fluoro-oxetan-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1224),

{3-[4-(3-amino-3-methylbut-1-inyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1225),

{3-[4-(5-cyclopropyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1226),

{3-[4-(5-cyclopentyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1227),

{3-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1228),

{3-[4-(5-isopropyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1229),

{3-[4-(5-tert-butyl[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1230),

{3-[4-(5-cyclohexyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1231),

(3-{4-[5-(3-methylbutyl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1232),

5-(3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}-[1,2,4]oxadiazol-5-ylmethyl)imidazolidin-2,4-dione (compound 1233),

(3-{4-[5-(4-methoxazole-5-yl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1234),

(3-{4-[5-(2,5-dimethyloxazole-4-yl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1235),

2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionitrile (connection 1236/1237),

2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1238),

2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1239),

[3-(4-methanesulfonyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1240),

2-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, methyl ester (compound 1241),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanol (compound 1242),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}methanesulfonamide (connection 1243),

{3-[4-(morpholine-4-sulfonyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1244/1245),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}ndimethylacetamide (connection 1246/1247),

3-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, methyl ester (compound 1248),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanesulfonamide (connection 1249/1250),

N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanesulfonamide (1251 connection),

N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzosulfimide (connection 1252/1253),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1254),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenoxy}acetic acid (compound 1255),

[3-(4-methanesulfonyl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine (compound 1256/1257),

N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}methanesulfonamide (connection 1258/1259),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}ndimethylacetamide (connection 1260/1261),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzyl}ndimethylacetamide (connection 1262/1263),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzyl}methanesulfonamide (connection 1264/1265),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}methanesulfonamide (connection 1266/1267),

[3-(4-methanesulfonyl)cycloheptyl]-((R)-1-naphthalene-1-retil)amine (compound 1268),

2-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohepta is]benzoic acid, methyl ester (compound 1269),

N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanesulfonamide (connection 1270),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}ndimethylacetamide (connection 1271/1272),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzyl}ndimethylacetamide (connection 1273/1274),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzyl}methanesulfonamide (connection 1275/1276),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenoxy}acetic acid ethyl ester (compound 1277),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}propionic acid methyl ester (compound 1278/1279),

N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanesulfonamide (connection 1280/1281),

{3-[4-(morpholine-4-sulfonyl)phenyl]cycloheptyl}-((R)-1-naphthalene-1-retil)amine (compound 1282),

{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanol (compound 1283),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, methyl ester (compound 1284),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, ethyl ester (compound 1285),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-morpholine-4-jatiluwih ester, dihydrochloride (compound 1286),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-(2-methoxyethoxy)ethyl complex the ether, hydrochloride (compound 1287),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-[2-(2-methoxyethoxy)ethoxy]ethyl ester, hydrochloride (compound 1288),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-[2-(2-ethoxyethoxy)ethoxy]ethyl ester, hydrochloride (compound 1289),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2,3-dihydroxypropyl ester, hydrochloride (compound 1290),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, tetrahydrofuran-2-ymetray ester, hydrochloride (compound 1291),

4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenol (compound 1292),

2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid, ethyl ester (compound 1293),

2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1294),

2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid (compound 1295),

3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}dihydrofuran-2-on (compound 1296),

(S)-{3R-[4-(2-ethoxyethoxy)phenyl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine (compound 1297),

3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid, ethyl ester (compound 1298),

4-(4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclo is Intel]phenoxymethyl}benzonitrile (connection 1299),

(S)-((R)-1-naphthalene-1-retil)-{3R-[4-(pyridine-3-ylethoxy)phenyl]cyclopentyl}amine (compound 1300),

(S)-((R)-1-naphthalene-1-retil)-{3R-[4-(2-pyrazole-1-ylethoxy)phenyl]cyclopentyl}amine (compound 1301),

(S)-(3R-{4-[2-(1H-indol-3-yl)ethoxy]phenyl}cyclopentyl)-((R)-1-naphthalene-1-retil)amine (compound 1302),

2-methyl-2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid hydrochloride (compound 1303),

4-hydroxy-2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1304),

2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid hydrochloride (compound 1305),

{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}phenylacetic acid, hydrochloride (compound 1306),

2-methyl-1-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propan-2-ol (compound 1307),

3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxymethyl}pentane-3-ol (compound 1308),

dimethyl-karamanova acid 4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl ester (compound 1309),

3-ethyl-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}pentane-3-ol (compound 1310),

2-methyl-4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}butane-2-ol (compound 1311),

3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propane-1,2-diol (compound 1312),

(2-perfe who yl)-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid, hydrochloride (compound 1313),

2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}ethanol, formate (compound 1314),

(1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}pyrrolidin-2-yl)methanol (compound 1315),

1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}pyrrolidin-3-ol (compound 1316),

1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}piperidine-3-carboxylic acid, ethyl ester (compound 1317),

[3-(4-{[methyl(tetrahydrofuran-2-ylmethyl)amino]methyl}phenyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1318),

3-(4-{(1S,3S)-3-[(R)-1-(4-fluoro-3-methoxyphenyl)ethylamino]cyclopentyl}phenyl)propionic acid, ethyl ester (compound 1319),

3-(4-{(1S,3S)-3-[(R)-1-(3-cyanophenyl)ethylamino]cyclopentyl}phenyl)propionic acid, ethyl ester (compound 1320),

3-{4-[(1S,3S)-3-((R)-1-benzo[b]thiophene-3-ylethylamine)cyclopentyl]phenyl}propionic acid ethyl ester (compound 1321),

3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethylamino]cyclopentyl}phenyl)propionic acid, ethyl ester (compound 1322),

3-{4-[(1S,3S)-3-((R)-1-phenylethylamine)cyclopentyl]phenyl}propionic acid ethyl ester (compound 1323),

3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzofuran-5-yl)ethylamino]cyclopentyl}phenyl)propionic acid, ethyl ester (compound 1324),

3-(4-{(1S,3S)-3-[(R)-1-(1H-Indo) - Rev.-7-yl)ethylamino]cyclopentyl}phenyl)propionic acid, hydroformed (connection 1325),

3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzo[1,4]dioxin-5-yl)ethylamino]cyclopentyl}phenyl)propionic acid, hydroformed (connection 1326),

3-(4-{(1S,3S)-3-[(R)-1-(1H-indol-4-yl)ethylamino]cyclopentyl}phenyl)propionic acid, hydroformed (connection 1327),

3-(4-{(1S,3S)-3-[(R)-1-(3-cyanophenyl)ethylamino]cyclopentyl}phenyl)propionic acid, hydroformed (connection 1328),

3-(4-{(1S,3S)-3-[(R)-1-(3-pyrrolidin-1-ylphenyl)ethylamino]cyclopentyl}phenyl)propionic acid, hydroformed (connection 1329),

3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzofuran-5-yl)ethylamino]cyclopentyl}phenyl)propionic acid, hydroformed (connection 1330),

3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1331),

3-(4-{(1S,3S)-3-[(R)-1-(4-fluoro-3-methoxy-1-ylphenyl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1332),

3-{4-[(1S,3S)-3-((R)-1-benzo[b]thiophene-3-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1333),

3-{4-[(1S,3S)-3-((R)-1-phenylethylamine)cyclopentyl]phenyl}propionic acid (compound 1334),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid, ethyl ester (compound 1335/1336),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1337),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1338),

1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoyl}piperidine-4-carboxylic acid, hydrochloride (compound 1340),

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoylamine}propionic acid hydrochloride (compound 1341),

4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid, methyl ester (compound 1342),

4-[3R-((R)-1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid, formate (compound 1343),

5-methyl-3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]-3H-imidazole-4-carboxylic acid (compound 1344),

(3S,4S-diphenylthiophene)-((R)-1-naphthalene-1-retil)amine (compound 1345),

5-(4-ethoxyphenyl-2-propylcyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1346),

[2-(4-forfinal)-5-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]acetic acid, hydrochloride (compound 1347) or

3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propan-1-ol (compound 1348).

Specific examples of the intermediate compounds for preparing compounds of formula I may be selected from the group consisting of the following compounds:

3-[3-(3-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclobutanol (connection 1112),

4-methyl-N-(3-oxocyclopentanecarboxylate)benzosulfimide (connection 1113),

3-(3-triptoreline)aminocyclohexane (connection 1114),

3-((R)-1-naphthalene-1-ylethylamine is)cyclohexanecarbonyl acid (preparation 4),

3-(4-itfinal)cyclohexane-1-he (preparation 5),

4-(3-oxocyclohexyl)benzaldehyde (preparation 7),

3-[4-((1S)-3-oxocyclopent)phenyl]propionic acid, ethyl ester (preparation 8),

3-[4-((1S,3R)-3-acetoxyacetyl)phenyl]propionic acid, ethyl ester (preparation 9),

3-[4-((1S,3R)-3-hydroxycyclopent)phenyl]propionic acid, ethyl ester (preparation 10),

3-[4-((1S,3R)-3-methanesulfonylaminoethyl)phenyl]propionic acid, ethyl ester (preparation 11),

4-((1S,4S)-4-acetoxysilane-2-enyloxy)benzoic acid, methyl ester (preparation 13),

4-((1S,4S)-4-hydroxycyclopent-2~enyloxy)benzoic acid, methyl ester (preparation 14),

4-((1S,4R)-4-harcelement-2-enyloxy)benzoic acid, methyl ester (preparation 15),

4-[(1S,4S)-4-((R)-1-naphthalene-1-ylethylamine)cyclopent-2-enyloxy]benzoic acid, methyl ester (preparation 16),

3-((1S,4S)-4-acetoxysilane-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 17),

3-((1S,4S)-4-hydroxycyclopent-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 18),

3-((1S,4R)-4-harcelement-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 19) or

5-methyl-3-[(1S,4S)-4-((R)-1-on the Talin-1 ylethylamine)cyclopent-2-enyl]-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 20).

The pharmaceutical composition

For use in therapy, the compounds according to this invention are typically in the form of pharmaceutical compositions. Therefore, the invention relates to pharmaceutical compositions, both for veterinary medicine (including mammals, such as horses, cattle, sheep, pigs, dogs and cats), and for medical use for humans, the composition comprises a compound of formula I, optionally together with one or more other therapeutically active compounds together with pharmaceutically acceptable excipient or carrier. Excipient must be "acceptable" in the sense of compatibility with other ingredients of the composition and safety for its recipient.

Conveniently, when the content of the active ingredient 0.05 to about 99.9% by weight of the composition, for example, 0.5 to 90%, such as 5-85%, such as 15-45%, preferably 20-30%.

The pharmaceutical compositions according to the invention can be in unit dosage form such as tablets, pills, capsules, powders, granules, elixirs, syrups, emulsions, capsules, suppositories or parenteral solutions or suspensions; for oral, parenteral, ocular, dermal, intra-articular, local, pulmonary, nasal, cheek or rectal injection or introduction of any other with the special suitable for the composition of the compounds used in Nephrology and in accordance with accepted practice, as disclosed inRemington: The Science and Practice of Pharmacy,21sted., 2005, Lippincott Williams & Wilkins. In the composition according to the invention, the active ingredient may be present in an amount of from about 0.01 to about 99%, such as from 0.1% to about 10% by weight of the composition.

For oral administration in the form of tablets or capsules of the compound of formula I may be suitably combined with non-toxic orally and pharmaceutically acceptable carrier, such as ethanol, glycerol, water or the like. In addition, appropriate binders, lubricants, dezintegriruetsja agents, flavoring agents and dyes can be added to the mixture properly. Suitable binders include, for example, lactose, glucose, starch, gelatin, gum acacia, tragacanth gum, sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes, or the like. Lubricants include, for example, sodium oleate, sodium stearate, magnesium stearate, sodium benzoate, sodium acetate, sodium chloride or the like. Dezintegriruetsja agents include, for example, starch, methylcellulose, agar, bentonite, xanthan gum or the like. Additional excipients for capsules include macrogol or lipids.

For preparing solid compositions, t is such as tablets, the active compound of formula I is mixed with one or more excipients, such as those mentioned above, and other pharmaceutical diluents, such as water, to get a solid pre-composition comprising a homogeneous mixture of compounds of formula I. the Term "homogeneous" should be understood as meaning that the compound of formula I is uniformly dispersed throughout the composition so that the composition can be easily divided into equally effective unit dosage forms such as tablets or capsules. Preliminary composition can then be divided into unit dosage forms containing from about 0.05 to about 1000 mg, in particular from about 0.1 to about 500 mg, for example, 10-200 mg, such as 30-180 mg, such as 20 to 50 mg of active compounds according to the invention.

In the form of a unit dose of the compound can be entered one or more times a day at appropriate intervals, always depending, however, on the patient's condition and in accordance with the regulations made by the attending physician. Usually a single dose of the composition contains between 0.1 mg and 1000 mg, preferably between 1 mg and 100 mg, for example, 5-50 mg of the compounds of formula I.

A suitable dosage of the compounds according to the invention will depend, among other things, on the age and condition of the patient, severity of the disease requiring treatment, and other factor is, a well-known practitioner. The connection can be injected or orally, or parenterally, or topically according to different dosing schedules, for example, daily or weekly intervals. Typically, a single dose will be in the range from 0.01 to 400 mg/kg of body weight. The connection can be injected as a bolus (i.e. total daily dose is administered at once or in separate doses two or more times per day.

If the treatment involves the introduction of another therapeutically active compounds, it is recommended to inquire about applicable dosages of these compounds in Goodman's The Pharmacological Basis of Therapeutics, 9thEd., J.G. Hardman and Limbird LE (Eds.), VcGraw-Hill 1995. Introduction compounds according to this invention with one or more other active compounds may be either simultaneous or sequential.

Liquid compositions either for oral or parenteral administration of the compounds according to the invention include, for example, aqueous solutions, syrups, aqueous or oil suspensions and emulsions with edible oils such as cottonseed oil, sesame oil, coconut oil or peanut oil. Suitable dispersing or suspendresume agents for aqueous suspensions include synthetic and natural gums, such as tragakant, alginate, gum acacia, dextran, sodium with the l carboxymethylcellulose, gelatin, methylcellulose or polyvinylpyrrolidone.

For parenteral administration, for example, intramuscular, intraperitoneally, subcutaneous or intravenous injection or infusion, the pharmaceutical composition preferably contains a compound of formula I dissolved or solubilization in the appropriate pharmaceutically acceptable solvent. For parenteral administration, the composition according to the invention may include sterile aqueous or non-aqueous solvent, in particular water, isotonic saline, isotonic glucose solution, buffer solution or other solvent commonly used for parenteral administration of therapeutically active substances. The composition may be sterilized, for example, by filtration through inhibiting bacteria filter, adding a sterilizing agent to the composition, by irradiation of the composition or by heating the compositions. Alternatively, the connection according to the invention can be provided in the form of sterile solid preparation, for example, dried by freezing powder, which is dissolved in sterile solvent immediately prior to use.

Composition intended for parenteral administration may additionally contain conventional additives, such as stabilizers, buffers or preservatives, for example, ant the oxidants, such as methylhydroxybenzoate, or the like.

Compositions for rectal injection can be in the form of a suppository containing an active ingredient and a carrier such as cocoa butter, or in the form of an enema.

Compositions suitable for intraarticular injection, can be in the form of a sterile aqueous preparation of the active ingredient, which may be in microcrystalline form, for example, in the form of an aqueous microcrystalline suspension. Liposomal compositions or biodegradable polymer systems can also be used to provide the active ingredient for both intra-articular and ocular injection.

Compositions suitable for topical administration, including eye treatment, include liquid and semi-liquid preparations such as liquid ointments, lotions, gels, applicants, emulsions of the type oil-in-water or water in oil, such as creams, ointments or pastes; or solutions or suspensions such as drops. For local administration of the compound of the formula I can generally present in amounts of from 0.01 to 20% by weight of the composition, for example, from 0.1% to about 10%, but may also be present in amounts up to about 50% of the composition. Compositions for the treatment of eyes can preferably further comprise a cyclodextrin.

Compositions intended for insertion into the nose or cheek cavity and is for inhalation, include powder, samospaseniyu or sprayable compositions, such as aerosols and spray guns. Such compositions may contain the compound of formula I in an amount of 0.01-20%, e.g. 2%, by weight of the composition.

The composition may further contain one or more other active ingredients commonly used in the treatment of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism.

A suitable dosage of the compounds according to the invention will depend, among other things, on the age and condition of the patient, the severity of the disease requiring treatment, and other factors well known to the practitioner. The compound may be administered orally, parenterally or topically according to different dosing schedules, for example, daily or weekly intervals. Typically, a single dose will be in the range from 0.01 to 400 mg/kg of body weight. The connection can be injected as a bolus (i.e. total daily dose is administered at once or divided doses two or more times per day.

Pharmacological methods

Susceptible to calcium receptor (CaSR) and its application for identifying or screening calcimimetics compounds described in EP 637237, EP 1296142, EP 1100826, EP 1335978 and EP 1594446.

In vitro and in vivo methods of test compounds on this from the retenu well established and can be found in the links listed above, or, for example, in the Journal of Biological Chemistry (2004), 279(8), 7254-7263 or US 5858684 and references cited therein.

Biological sample for analysis activity in vitro

The test examines the functional ability of compounds to act as a biological positive modulator of CaSR man. Activation of the receptor, expressed on cells Cho-K1, determine the way through G alpha q, the activation of phospholipase C and intracellular accumulation of insiststhat (IP), as described previously [Sandrine Ferry, Bruno Chatel, Robert H. Dodd, Christine Lair, Danielle Gully, Jean-Pierre Maffrand, and Martial Ruat, Effects of is divalent Cations and of a Calcimimetic on Adrenocorticotropic Hormone Release in Pituitary Tumor Cells. Biochemical and biophysical research communications, 238, 866-873 (1997)]. CaSR person consistently expressyour on the cell clone Cho-K1, stimulate basic level of calcium and provoke the test connection. Level IP1 is determined using the set IP-One htrf (Cisbio, France). Cells Cho-K1, is not subjected to transfection with the use of CaSR, not enough to cause a reaction IP1 on stimulation with calcium and/or connection.

Cloning of the geneCaSRman

ORF encoding human CaSR, (gene Bank: NM_000388) was purchased from Invirtro Corp., USA, and then cloned in expressing vector mammal pCDA3.1.

Generation of cell lines expressing CaSR

Cells Cho-K1 were subjected to transfection with the use of lipofectamine according to the Protocol of the manufacturer (400,000 cells/well were sown in 6-well plate and after 24 hours were subjected to transfection using 2 μg DNA and 5 μl of lipofectamine). After another 24 hours the cells were separated, were sown and were subjected to 1 mg/ml G-418. After 7 days growth of individual clones were collected, CaSR expression was evaluated using antibodies S against CaSR, the clones with the highest expression were selected and tested on the functional response. The preferred clone continuously cultivated according to standard procedures described in the protocols of ATS (American collection of typical crops) for Cho-K1, with the addition of 500 μg/ml G-418.

As indicated above, the compounds described in this application for the invention are modulators of the activity of the CaSR. CaSR can be found in the parathyroid gland, thyroid gland, bone cells, stomach, lung, kidney, pituitary, brain, hypothalamus, olfactory fields of the hippocampus. Compounds according to this invention may preferably be more selective in their application in relation to the receptor of the parathyroid gland compared with receptors of the thyroid gland.

Compounds according to this invention and containing the pharmaceutical composition can be used as a medical product, in particular, for the treatment of physiological disorders or diseases associated with disturbances of CaSR activity. More specifically, these physiological disorders or diseases, including primary and periclymenoides, osteoporosis, cardiovascular, gastrointestinal, endocrine or neurodegenerative diseases or certain types of cancer, in which the content of ions (CA2+)eis abnormally high. Secondary hyperparathyroidism is particularly common in chronic renal failure.

Methods of producing and non-limiting examples are given to enable the specialist to understand and implement the invention.

Examples are described in more detail in the following non-limiting examples are not intended to in any way limit the scope of the claimed invention, but are considered merely as illustrative and typical.

Ways to get

Compounds of General formula I can be obtained in different ways, known to experts in the field of organic synthesis. Compounds of General formula I can be synthesized using the methods described in General terms below, along with methods known in the field of organic chemistry, or their variants, as it is clear to the experts in this field. Preferred methods include those described below, but not limited to.

The compounds of formula I can be obtained by techniques and procedures readily available to the specialist, for example, by the following procedures, which are shown in the following with the Emax. The reaction is carried out in a solvent corresponding to the used reagents and materials and suitable for the ongoing transformations. In addition, the following synthesis methods, as it must be understood that all proposed reaction conditions, including choice of solvent, reaction atmosphere, reaction temperature, duration of the experiment and processing procedures, are chosen so that these conditions were the norm for that reaction, which should be quite obvious to the expert. Specialist in the field of organic synthesis it is clear that the functional groups present on different parts of the original molecules in the reaction must be compatible with the proposed reagents and reactions. Not all compounds of formula I in this class may be compatible with some of the reaction conditions required in some of the described methods. Such restrictions to the substituents that are compatible with the reaction conditions will be obvious to a specialist, and can be used in alternative methods.

The scheme described in this section are not intended to limit the scope of the invention, one way or another. All substituents, unless otherwise indicated, are previously defined. The reagents and starting materials on or available from commercial vendors, or obtained by methods known conventional JV is the expert, following the procedures explained in the references, such as Feiser and Feiser's Reagent for Organic Synthesis, Volumes 1-22 (John Willey and Sons, 2004); Rodd''s Chemistry of Carbon Compounds, Volumes 1-5 and Supplements (Elselvier Science Publishers, 2000); Organic Reactions, Volumes 1-64 (John Willey and Sons, 2004); March's Advanced Organic Chemistry (John Willey and Sons, 5thEdition) and Larock''s Comprehensive Organic Transformations (VCH Publishers Inc., 1999). These schemes simply explain some of the ways can be synthesized compounds according to the invention, and various modifications to these schemes can be made and the proposed disposal of a specialist in the field of technology pertaining to this disclosure. Raw materials and intermediate compounds reactions can be isolated and purified, if desired, using conventional techniques, including, but not limited to, filtration, distillation, crystallization, chromatography and the like. Such materials can be characterized using conventional means, including physical constants and spectral data.

Compounds of General formula I can be obtained by reductive amination between cyclic ketone of General formula II and the amine of General formula III. The reaction between the ketone II and the amine III can be carried out, or by reductive amination in the same reactor, or emitting imine, followed by reduction.

a. Education is Finance intermediate imine IV can be promotioanl the addition of a proton or a Protic acid, such as, but without limitation, acetic acid and Ti(Oi-Pr)4, respectively. The reducing agent may be, but without limitation, Na(CN)BH3, NaBH4, Na(OAc)3BH (for other non-limiting conditions seeOrg. React.2002, 59, 1-714 and references cited there).

b. The formation of imine promotirovat or Lewis acids, such as TiCl4, ZnCl2, AlCl3or bases, such as pyridine, possibly in the presence of a drying agent, such as TiCl4or molecular sieves (seeComprehensive Organic Functionnal Group Transformations 3,403 (1995) Pergamon).

c. The recovery may be carried out by hydrogenation in the presence of a catalyst such as Pd/C, Pt/C or chiral rhodium complex to carry out the reaction is stereoselective manner, or by hydride transfer from a reducing agent, such as BH3, NaBH4, NaBH3CN, LiAlH4L-selectride (see Larock, R. C.Comprehensive Organic Transformations 1989,VCH;Comprehensive Organic Functionnal group Transformations 2,268-269 (2005) Pergamon and references cited there).

Compounds of General formula I can also be obtained by alkylation of amine III.

LG = leaving group (leaving group)

d. When LG denotes a leaving group such as chloride, bromide, iodide, tosylate or triflate, the alkylation is carried out in the presence of a base, such as NEt3, DIPEA, NaH, NaOH, KOH, carbonates, in choosing the appropriate solvent, such as DMF, pyridine, DMSO, CH3CN, acetone, toluene. As an option can be considered also the reaction with alcohol (LG=OH). Such a reaction similar to the reaction Mitsunobu, carried out in the presence of a phosphine, such as PBu3, PPh3and the like, azodicarboxylate or isocarboxazid in an aprotic solvent, typically THF. To this end amine III protect/activate as carbamate or sulfonamide. The compound obtained is freed from the protective groups, using standard conditions(Protective Groups in Organic Synthesis,T.W. Greene and P.G.M. Wuts, John Wiley and Sons, 3rdEdition, 1999 and references cited therein), to obtain compound I.

The ketone II can be obtained in different ways:

LG=OH

e. The Va alcohol can be oxidized to obtain compound II. The oxidation can be carried out in many different reagents. Some of them are H2Cr2O7, Al2O3, MnO2, periodinane, DMSO in combination with DCC, acetic anhydride, oxalicacid and the like.

Deputy G can be entered in different ways:

Cycloalkane can be used as starting materials.

f. The reaction mix with aryl/heteroaryl a halide or pseudohalogen, such as triflate, in the presence of a palladium source such as Pd(OAc) , PdCl2(PPh3)2, bases, such as NEt3, K2CO3, NaHCO3possibly with a phosphine, such as PPh3, P(o-Tol)3, 1,3-bis(diphenylphosphino)propane (dppp), possibly in the presence of salts, such NBu4Cl, AgNO3in a solvent such as DMF or acetonitrile. As an option, can be carried out decarboxylase combination Heck-type with the use of aryl/heteroaryl carboxylic acid(Org. Lett.2004, 6, 433).

g. Chemospecific the restoration of the double bond can be carried out in appropriate conditions. The source of hydrogen can be H2water, Hantzsch esters. Catalysts based on metal, such as Pd/C, Pd(PPh3)4, PdCl2on the media, catalysts based on Rh, Co, Cu, Ir can be used. Stereoselectivity can be achieved by adding a chiral auxiliary substances, such as, but without limiting the above, enantiomerically pure binaphthol derivative phosphate/valine, imidazolidine imini, bidentate phosphines.

Alternatively cycloalkane can be subjected to 1,4-connection.

h. Reaction with aryl/heteroaryl metal in which the metal can serve as Li, Mg halide, triamcinolone, baronova acid, possibly in the presence of a complex metal such as PdCl2Pd(OAc)2Pd(PPh3)4, (acac)Rh(CO)2Ni(acac) 2, (COD)Rh(1,4-dihydrogen)BF4with the ligand, usually on the basis of a phosphine, such as PBu3, PPh3, 1,3-bis(diphenylphosphino)propane (dppp), 1,3-hydroquinone or 1,4-hydroquinone, in solvents such as DMF, THF, water, toluene, dioxane, dimethoxyethane. In the presence of a chiral ligand as a pure enantiomer, such as BINAP, phosphoramidite, Me-DuPHOS and the like, the reaction can be carried out stereoselective.

1,4-Addition of heteroatomic nucleophiles leads to compounds of General formula I. the Reaction can be catalyzed by reagents such as, but without limitation, NEt3, ScCl3, CAN RuCl3, PtCl4in solvents of the type CH2Cl2CH3CN, DMF, toluene.

Cycloalken-l,3-diones can be used as starting materials.

i. Join ORGANOMETALLIC compounds, such as GLi or GMgHal (Hal=Cl, Br) gives cytosport II (R4=OH). Alternatively, the accession of the GBr during the catalysis of indium can lead to the same caespitum II (R4 = OH).

j. Substitution of the leaving group (LG)such as chloride, bromide, iodide, tosylate or triflate, a nucleophile such as an amine or an alcohol, optionally in the presence of a base, such as NEt3, NaH, NaOH, KOH, carbonates, in an appropriate solvent, such as DMF, pyridine, DMSO, CH3CN, AC is the tone, the toluene.

Cycloalken-3-one carboxylates (II, G=CO-Q) are the starting materials for a variety of compounds of General formula I, where the carboxyl group is converted into amides or heterocycles. Some non-limiting examples below.

k. Amide can be formed using an amine and a carboxylic acid (II, G=COOH) in the presence of the agents of the combination, such as 1,1'-carbonyldiimidazole (CDI), diphenylphosphinic chloride (DPP-Cl), benzothiazolylsulfenamide hexaflurophosphate (PyBOP), benzotriazol-1 yloxy-Tris(dimethylamino)phosphonium hexaflurophosphate (BOP), pentafluorophenyl diphenylphosphine (fdpp),N[(dimethylamino)-1H-1,2,3-triazolo[4,5-b]pyridine-1-ylmethylene]-N-methylmethanamine hexaphosphate N-oxide (HATU), patrimonialization hexaflurophosphate (PyBroP), N,N'-dicyclohexylcarbodiimide (DCC) or 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, hydrochloride (EDCL). The reaction can be carried out in solvents, such as diethyl simple ether, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, 1-methyl-2-pyrrolidinone, dimethyl sulfoxide or dimethylformamide. The reaction is usually carried out in the presence of a base, such as NEt3, DIPEA, kallidin or Bu3N, and preferably in the presence of an activator, such as HOBt (for example, where HOBt is used to enhance reaction rates, see indridge, G. C.; Jorgensen,E. C. JACS1971,93,6318) or HOAt.

Amide may also be formed in the interaction of amine III and the acid chloride of the carboxylic acid (II, G = COCl). The acid chloride of the carboxylic acid can be obtained by the reaction of carboxylic acid (II, G=COOH) with gloriously agents such as thionyl chloride or oxalicacid.

I. Carboxyl group can be converted into a oksazolov by the reaction of 1,2-aminoalcohols, 1,2-aminoketone or 1,2-hydroxyketone in the presence of a nitrogen source, such as NH4OAc, usually through the formation of amide (see condition (k) with subsequent cyclodehydration using reagents, such as polyphosphoric acid, p-toluensulfonate acid, DBU/CBrCl3or DDQ, in solvents, such as CCl4CH2Cl2, THF, dioxane or DMF.

m. The transformation in 1,2,4-oxadiazol can be carried out by reaction withN-ghydroxylamine in the conditions of formation of amide linkages (see k) with subsequent cyclodehydration in the presence of a dehydrating agent, such as CDI. Alternatively, the interaction of esters of carboxylic acids (II, G=COOMe or COOEt) N-hydroxyamine in the presence of a base, such as K2CO3leads to 1,2,4-oxadiazole. If N-hydroxyamides not commercially available, they can be obtained by reaction of N-hydroxylaminopurine with what frilli in the presence of a base, such as the K2CO3, NaHCO3NEt3, KOH or MeONa.

If you need a specific pattern of substitution on carbocycle may be a synthesis of carbocycles. Many conventional methods available, among them the Diels-alder reaction, the formation of rings by Robinson, recovery of aromatic compounds in Birch, the reaction of the Pauson-Khand, cyclopropylamine 1-methoxycyclohexene with subsequent expansion of the ring, the rearrangement furans. To get a complete list, see the comprehensive works on organic synthesis, cited earlier in this section.

The compound of General formula I can be obtained from the other compounds of General formula I via the interconversion of functional groups, a well-known specialist in the field of organic synthesis. That is, any group of R1-R5 or Deputy on G or on A can be converted into another functional group. These interconversions can be, but not limited to, the restoration of the nitrile to the amine, the hydrolysis of nitrile to amide or until the acid or hydrolysis of ester.

Many conventional methods described above can be used in a different order when it is appropriate.

EXAMPLES

Total

For the spectrum of1H nuclear magnetic resonance (NMR) (300 MHz) and13C NMR (75,6 MHz) is elicina chemical shifts (δ) (in ppm) are given for solutions of dimethyl-d 6sulfoxide (DMSO-d6or CDCl3in relation to internal tetramethylsilane standard (δ=0). The magnitude of the multiplet, whether a certain (doublet (d), triplet (t), Quartet (K))or not (m), given at approximately the midpoint, if the range is not specified, (sh) refers to a broad singlet. Mass spectrum ES received on a triple quadrupole mass spectrometer VG Quattro II (Micromass, Manchester, UK)operating in either a positive or negative elektrorazpredelenie with a cone voltage of 30 Century Used a microwave was a model Initiator™ from Biotage. Organic solvents used anhydrous, unless otherwise noted. Flash chromatography was performed on silica gel from Fluka Chemie GmbH, Switzerland. Used cartridges for phase separation were Chromabond® from Macherey-Nagel GmbH.

Chemicals unless otherwise stated, were from commercial sources such as Aldrich, Maybridge Chemical, Fluka or ABCR.

Reduction

acacacetylacetonate
aq.water
BINAP2,2'-bis(diphenylphosphino)-1,1'-binaphthyl
Boctert-butoxycarbonyl
B 3Ntributylamine
CANmixed cerium nitrate and ammonium
CDI1,1'-carbonyldiimidazole
COD1, 5cyclooctadiene
DBU1,8-diazabicyclo[5,4,0]undec-7-EN
DCCN,N'-dicyclohexylcarbodiimide
DCE1,2-dichloroethane
DCMdichloromethane
DDQ2,3-dicyano-5,6-dichlorobenzophenone
DIADdiisopropylsalicylic
DIPEAethyldiethanolamine
DMAPdimethylaminopyridine
DMFN,N-dimethylformamide
DME1,2-dimethoxyethan
DMSOthe sulfoxide
EDACEQ.equivalent(s)
ESelektrorazpredelenie

EtOActhe ethyl acetate
hhour(s)
HOAt1-hydroxy-7-asobancaria
HOBthydroxybenzotriazole
mCPBAmetachlorobenzoic acid
Me-DuPhos1,2-bis[2,5-dimethylmorpholine]benzene
MTBEmethyl tert-butyl simple ether
nbdnorbornadiene
NBu4Cltetrabutylammonium
NEt3the triethylamine
NMRnuclear magnetic Resonans
PBu3tributive is n
PEpetroleum simple ether (low boiling point)
P(o-Tol)3three(o-tolyl)phosphine
K.T.room temperature
RTretention time
us.rich
THFtetrahydrofuran
Ti(Oi-Pr)-4tetraisopropoxide titanium
TLCthin-layer chromatography
TMSClchlorotrimethylsilane

LC/MS Method A

Analytical HPLC/MS was performed on a Dionex APS system with analytical pump P680A and mass spectrometer Thermo MSQ Plus (mode ionization: ES+/ES-). Column: Waters XTerra C-18, 150 mm×4.6 mm, 5 μm; mobile phase: A = water with 0.1% formic acid) and B = acetonitrile with 0.1% formic acid); flow rate = 1.0 ml/min; method (10 min): the method is linear changes in gradient from 10% B to 100% for 6.6 minutes and leaving at 100% B for the next 1.5 minutes.

LC/MS Method B

Analytical HPLC/MS was performed on a Waters 2795 Alliance system with the analyte is ical pump, Waters 996 DAD and a mass spectrometer Waters ZQ (mode ionization: ES+/ES-). Column: Waters Waters XBridge RP18 a 3.0×50 mm, 5 μm; mobile phase: A = H2O is + 0.05% HCOOH and B = CH3CN is + 0.05% HCOOH, flow rate = 1.0 ml/min; method (8 min): method linear changes in gradient from 5% B to 95% B in 6 minutes and leaving at 95% B for 1 minute. Retention time on the UV chromatogram (RT) is given in minutes.

General procedure A

To a solution of ketone (1 EQ.) in 1,2-dichloroethane (0,38 M) was added the amine (1 EQ.), ice AcOH (1 EQ.) and NaBH(OAc)3(1.4 EQ.). The mixture was stirred at K.T. over night, filtered and concentratedin a vacuum.If necessary, the purification was performed by flash chromatography with a continuous gradient.

Example 1:Cyclobutyl-((R)-1-naphthalene~1-retil)amine, hydrochloride (compound 1001)

Followed General procedure A, using cyclobutanone (488 mg, 1.2 EQ.) and (+)-(R)-1-naphthalene-1-ylethylamine (1 g). The solution was stirred for 10 min before adding molecular sieves 3Å, glacial AcOH and NaBH(OAc)3. After removal of solvent the residue was taken in MeCN (20 ml) and was treated with aq. 2 N. NaOH (10 ml), filtered and concentratedin a vacuum.The residue was dissolved in EtOAc, washed with water, filtered and concentratedin a vacuum.Chromatography (EtOAc-MeOH 100:0 to 80:20) gave specified in the header of the connection.13C NMR (75.5 MHz, DMSO) δ: 134,58, 133,71, 130,61, 129,29, 129,25, 127,27, 126,48, 125,86, 125,06, 122,82, 50,43, 50,16, 26,90, 20,63, 15,19.

Overall the I procedure B

To the solution or suspension of the acid (1 EQ.) in DMF (1M) in an argon atmosphere was added CDI (1.2 EQ.). The mixture was stirred at K.T. for 3 h before adding the amine (6 EQ.). DIPEA (6 EQ.) added, if the amine was prepared as the hydrochloride. Stirring was continued over night at K.T. DMF was removedin a vacuum.If necessary, the purification was performed by flash chromatography with a continuous gradient.

Preparation 1:3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (compound 1000)

To a solution of 3-oxo-1-cyclobutanecarboxylic acid (4.0 g) in 1,2-dichloroethane (180 ml) was added (+)-(R)-1-naphthalene-1-ylethylamine (6.0 g), glacial AcOH (1 EQ., 2,1 ml) and NaBH(OAc)3(1.5 EQ., 11.1 g). The mixture was stirred at K.T. within 48 h before removing the solvent. The residue was treated with 1 N. NaOH (ca 100 ml) and the pH was brought to 7 by addition of 4 N. HCl. The oily precipitate was extracted with EtOAc. The solid formed after extraction was filtered and washed with EtOAc to obtain specified in the header of the connection.

Example 2:dimethylamide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1002)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and dimethylamine hydrochloride (181 mg). Chromatography (CH2Cl2-MeH/1% NEt 3100:0 to 70:30) gave specified in the title compound as an oil (mixture of 2 isomers).13C NMR (75.5 MHz, DMSO) major isomer δ: 174,53, 140,84, 133,98, 131,12, 129,02, 127,40, 125,87, 125,69, 125,36, 123,06, 122,79, 51,12, 49,31, 36,71, 35,48, 33,38, 32,84, 31,59, 23,35.

Example 3:amide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1003)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 155 mg) and aq. NH3(2.5 ml). Chromatography (CH2Cl2-MeOH 90:10 to 70:30) gave specified in the header connection. LC-MS (method B): RT = 1,53, [M+H]+= 269,3, [M-H]-= 267,4.

Example 4:hydrochloride (4-methylpiperazin-1-yl)-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]methanone (compound 1004)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and N-methylpiperazine (3 EQ.) Extractive processing (EtOAc and water) was carried out before chromatography (CHZCl2-MeOH 95:5 to 70:30). The obtained oil was treated with HCl. The precipitate was filtered, receiving specified in the header connection. LC-MS (method B): RT = 1,37, [M+H]+= 352,3.

Example 5:cyclopropylamino 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1005)

SL is followed General procedure, using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and cyclopropylamine. Chromatography (CH2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the header connection. LC-MS (method B): RT = 2,2, [M+H]+= 309,3.

Example 6:isopropylated 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1006)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and Isopropylamine. Chromatography (CH2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the header connection. LC-MS (method B): RT = 2,3, [M+H]+= 311,3.

Example 7:propelled 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1007)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and Propylamine. Chromatography (CH2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the header connection. LC-MS (method B): RT = 2,3, [M+H]+= 311,1.

Example 8:morpholine-4-yl-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1008)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 10 mg) and morpholine. Chromatography (CH2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the title compound in the form of oil. LC-MS (method B): RT = 2,16, [M+H]+= 339,3.

Example 9:tert-butylamide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1009)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and tert-butylamine. Chromatography (CH2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the title compound in the form of oil. LC-MS (method B): RT = 2,6, [M+H]+= 325,3.

Example 10:ethylamide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1010)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and ethylamine. Chromatography (CH2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the title compound in the form of oil. LC-MS (method B): RT = 2,13, [M+H]+= 297,2.

Example 11:hydrochloride methoxyethylamine 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1011)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 100 mg) and the hydrochloride of N,O-dimethylhydroxylamine. cromatografia (CH 2Cl2-MeOH/1% NEt3100:0 to 70:30) gave specified in the title compound in the form of oil. LC-MS (method B): RT = 2,17/2,31, [M+H]+= 313,2.

General procedure C

To the solution or suspension of the acid (1 EQ.) in DMF (1M) in an argon atmosphere was added CDI (1.2 EQ.). The mixture was stirred at K.T. within x hours before adding N-hydroxyamide (1.2 EQ.). Stirring is continued at K.T. within y hours CDI (1.2 EQ.) was added and the mixture was heated to 115°C for 1.5 h the Mixture was cooled to K.T., washed with water, NaHCO3and saturated salt solution, dried over MgSO4, filtered and concentrated in vacuum.If necessary, the purification was performed by flash chromatography with a continuous gradient.

Example 12:hydrochloride [3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)cyclobutyl]-((R)-1-naphthalene-1-retil)amine (compound 1012)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 150 mg) and N'-hydroxy-2-methylpropanamide (x = 3 h, y = 48 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. light yellow precipitate was filtered and dried in vacuum,getting listed at the beginning of the connection.13C NMR (150,9 MHz, DMSO) δ: 180,68, 174,28, 133,70, 133,25, 130,19, 129,05, 128,86, 126,90, 126,13, 125,43, 14,68, 122,45, 50,23, 48,16, 39,97, 30,09, 25,92, 25,72, 20,09.

Example 13:hydrochloride ((R)-1-naphthalene-1-retil)-{3-[3-(3-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclobutyl}amine (compound 1013)

Followed General procedure C, using 3-oxo-1-cyclobutanecarbonyl acid (1,41 g, 12.4 mmol) and 3-trifluoromethyl-N-hydroxybenzamide (x = 1 h, y = 17 h). Chromatography (PE-EtOAc 80:20 to 70:30) gave 3-[3-(3-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclobutanol (connection 1112).

Followed General procedure A, using 3-[3-(3-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclobutanol (690 mg) and (+)-(R)-1-naphthalene-1-ylethylamine. The mixture was processed as follows. To the reaction mixture was added Et2O. the Organic phase is washed with aq. NaOH (1 ad), water and saturated salt solution, dried over MgSO4, filtered and concentrated in vacuum.Chromatography (PE-EtOAc 80:20 to 60:40) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O and rubbing. The colorless precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS(method B): RT = 3,28, [M+H]+=438,2.

Example 14:hydrochloride [3-(3-methyl-[1,2,4]oxadiazol-5-yl)cyclobutyl]-((R)-1-naphthalene-1-retil)amine (compound 1014)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclebut karbolovuju acid (preparation 1, 150 mg) and N'-hydroxyethylamide (x = 2 h, y = 48 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O and rubbing. Light yellow precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS (method B): RT = 2,31, [M+H]+= 308,2.

Example 15:hydrochloride ((R)-1-naphthalene-1-retil)-[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclobutyl]amine (compound 1015)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 150 mg) and benzamidoxime (x = 2 h, y = 22 h). Chromatography (PE-EtOAc 100:0 to 50:50) gave a light yellow oil, which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. the Precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS (method B): RT = 3.04 from, [M+H]+= 370,3.

Example 16:hydrochloride ((R)-1-naphthalene-1-retil)-{3-[3-(4-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclobutyl}amine (compound 1016)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 150 mg) and 4-triftormetilfosfinov (x = 2 h, y = 22 h). Chromatography (PE-EtOAc 100:0 to 50:50) gave an oil which was treated with 4 N. HCl in dioxane. The deposition of p is oishodilo adding Et 2O. the Precipitate was filtered and dried in vacuum,receiving specified in the header connection. LC-MS (method B): RT = 3.52, the [M+H]+= 438,2.

Example 17:hydrochloride {3-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]cyclobutyl}-((R)-1-naphthalene-1-retil)amine (compound 1017)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (preparation 1, 150 mg) and 4-methoxybenzamide (x = 1 h, y = 22 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. the Precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS (method B): RT = 3,14, [M + H]+= 400,3.

Preparation 2:3-Oxocyclopentanecarboxylate

Oxalicacid (1.5 EQ.) was added dropwise to a solution of 3-oxocyclopentanecarboxylate acid (56 mmol) in CH2Cl2and DMF (1 drop) in an argon atmosphere. The solution was stirred at K.T. for 30 min, then concentrated in vacuo,give crude 3-oxocyclopentanecarboxylate used without further purification.

General procedure D

To a solution of carboxylic acid (preparation 2, 1.2 mmol) in 1,2-dichloroethane (0.5 ml) was added amine (1.2 mmol) as CH2Cl2-solution (1 ml) and NEt3(1.5 EQ.). The mixture was which when K.T. than is their night. a 0.5 M aqueous HCl (0.5 ml) was added and the mixture was which when K.T. within 2 hours Filtering through the cartridge for separation of the phases gave the organic phase, which was concentrated in vacuum to give crude amide, which is used without further purification.

To a solution of amide (1.2 mmol) in 1,2-dichloroethane (1 ml) was added (+)-(R)-1-naphthalene-1-ylethylamine (1 EQ.) and glacial AcOH (2 EQ.). The mixture was which for 2 h before adding NaHB(OAc)3(1.5 EQ.). Stirring was continued at K.T. overnight before being filtered and concentrated in vacuum.The residue was dissolved in DMSO (1 ml). 0.1 ml of this solution was purified preparative HPLC-MS, re-analyzed by HPLC-MS, method A.

Example 18:4-Chlorobenzilate 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1018)

Followed General procedure D using 4-chlorobenzylamino, getting mentioned in the title compound as a mixture of 2 isomers in equal amounts. LC/MS (METHOD A): (m/z) 393,1 (MH+); RT (UV) = 5,11 minutes1H NMR (500 MHz, DMSO) δHcompared to 8.26 (t, 1H), 8,14-to 8.20 (m, 1H), to $ 7.91 (d, 1H), 7,78 (d, 1H), to 7.67 (t, 1H), 7,42-7,56 (m, 3H), 7,33 (DD, 2H), 7,19 (DD, 2H), 4,49 with 4.64 (m, 1H), 4,18 (DD, 1H), 2,80-3,03 (m, 2H), 1,79-of 2.24 (m, 4H), of 1.36 (d, 3H) (one CH obscured by water signal). LC-MS (method B): RT 5,11, [M+H]+=393,1.

Example 19:methyl ester {[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}acetic acid the acid (compound 1019)

Followed General procedure D, using the hydrochloride of ester methyl 2-aminouksusnoy acid. LC-MS (method B): RT = 4,32, [M+H]+= 341,0.

Example 20:(2-methoxyethyl)amide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1020)

Followed General procedure D using 2-methoxyethylamine. LC-MS (method B): RT = 4,12, [M + H]+= 327,1.

Example 21:ethyl ester of 4-{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}benzoic acid (compound 1021)

Followed General procedure D, using the ethyl ester of 4-aminobenzoic acid. LC-MS (method B): RT = 5,12, [M+H]+= 417,2.

Example 22:(2,6-dimethylmorpholine-4-yl)[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1022)

Followed General procedure D, using 2,6-dimethylmorpholine. LC-MS (method B): RT = 4,56, [M+H]+= 367,1.

Example 23:(3-morpholine-4-ylpropyl)amide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1023)

Followed General procedure D using 1-morpholino-3-aminopropan. LC-MS (method B): RT = 3,54, [M+H]+= 396,2.

Example 24:ethyl ester 1-[3-((R)-1-naphthalene~1 ylethylamine)cyclobutanecarbonyl]piperidine-4-carboxylic KIS is the notes (compound 1024)

Followed General procedure D using ethyl ester piperidine-4-carboxylic acid. LC-MS (method B): RT = 4,81, [M+H]+= 409,2.

Example 25:(2-hydroxy-2-phenylethyl)amide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1025)

Followed General procedure D using 2-hydroxy-2-phenylethylamine. LC-MS (method B): RT = 4,59, [M+H]+= 389,1.

Example 26:ethyl ester of 3-{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}propionic acid (compound 1026)

Followed General procedure D, using the hydrochloride of ethyl ether complex 3-aminopropionic acid. LC-MS (method B): RT = 4,57, [M+H]+= 369,1.

Example 27:[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl][4-(3-triptoreline)piperazine-1-yl]metano (compound 1027)

Followed General procedure D using 4-(3-triptoreline)piperazine. LC-MS (method B): RT = 5.56mm, [M+H]+= 482,1.

Example 28:methyl ester {[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid (compound 1028)

Followed General procedure D, using the hydrochloride of the methyl ether complex (R)(-)-2-phenylglycine. LC-MS (method B): RT = 4,86, [M+H]+= 417,1.

Example 29: (2-hydroxyine-1-yl)amide 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1029)

Followed General procedure D, using (1S,2R)-(-)-CIS-1-amino-2-indanol. LC-MS (method B): RT = 4,67, [M+H]+= 401,2.

Example 30:[4-(2-methoxyethyl)piperazine-1-yl]-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1030)

Followed General procedure D using 4-(2-methoxyethyl)piperazine. LC-MS (method B): RT = 3.52, the [M+H]+= 396,2.

Example 31:2,3,6-triptoreline 3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarboxylic acid (compound 1031)

Followed General procedure D using 2,3,6-triptorelin. LC-MS (method B): RT = 4,99, [M+H]+= 413,1.

Example 32:methyl ester 3-({[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}methyl)benzoic acid (compound 1032)

Followed General procedure D, using the hydrochloride of the methyl ether complex 3-aminometilbensana acid. LC-MS (method B): RT = 4,81, [M+H]+= 417,1.

Example 33:methyl ester of 4-({[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}methyl)benzoic acid (compound 1033)

Followed General procedure D using methyl ester 4-aminomethylbenzoic the th acid. LC-MS (method B): RT = 4,79, [M+H]+= 417,1.

Example 34:{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid (compound 1034)

To a solution of ester methyl {[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid (Sp. 28, 1.2 mmol) in MeOH (1 ml) was added water (0.3 ml) and LiOH (10 equiv.). The mixture was which when K.T. during the night. Aqueous HCl (4 BC) was added until pH=5. The solvent decantation and the remaining oil is washed with EtOAc, dried in vacuumand was purified preparative HPLC-MS. LC-MS (method B): RT = 2,47, [M+H]+= 403,3, [M-H]-= 401,4.

Example 35:((R)-1-naphthalene-1-retil)-(3-phenylcyclohexyl)amine (compound 1035 and 1036 connection)

Followed General procedure A, using 3-vinylcyclopentane (1.0 g)and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:80:20) gave specified in the title compound (compound 1035) and indicated in the title compound (compound 1036). LC-MS (method B): compound 1035: RT = 2,22, [M+H]+= 302,2; 1036 connection: RT = 2,28, [M+H]+= 302,2.

Preparation of 3:3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (compound 1111)

To a solution of 3-oxo-1-cyclopentanecarboxylic acid (5.3 g) in 1,2-dichloroethane (100 ml) was added (+)-(R)-1-naphthalene-1-ylethylamine (7,1 g), glacial AcOH (1 EQ., 2.4 ml) and NaBH(OAc)sub> 3(1.5 EQ., of 13.1 g). The mixture was stirred at K.T. for 4 h before removing the solvent. The residue was treated with saturated aqueous NaHCO3pH was brought to 7 by addition of ice-cold AcOH. Extraction (5 times) was carried out with EtOAc. The combined extracts were dried over MgSO4, filtered and concentrated in vacuo,getting an oil, which after trituration in EtOAc was deposited. Filtration gave specified in the header of the connection.

the pH of the aqueous phase was brought to 6 by addition of 4 N. HCl, after settling has occurred deposition. Filtration gave optionally specified in the header of the connection.

Example 36:hydrochloride {3-[3-(4-forfinal)-[1,2,4]oxadiazol-5-yl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine (compound 1037)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 205 mg) and N'-hydroxy-(4-forfinal)imitated (x = 24 h, y =5 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. light yellow precipitate was filtered and dried in vacuum,getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δH: 10,22 (s, 1H), 9,60 (s, 1H), 8.34 per (d, 1H), to $ 7.91-to 8.14 (m, 6H), 7,54-7,73 (m, 3H), 7,30-7,47 (m, 2H), are 5.36 (K, 1H), 3,74-3,93 (m, 1H), 3,50 at 3.69 (m, 1H), 2.21 are of 2.44 (m, 3H), 1,95-to 2.18 (m, 2H), of 1.78-1.90 (m, 1H), a 1.75 (d, 3).

Example 37:hydrochloride ((R)-1-naphthalene-1-retil)-[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]amine (compound 1038)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 205 mg) and benzamidoxime (x = 24 h, y = 5 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. light yellow precipitate was filtered and dried in vacuum,receiving specified in the header connection. LC-MS (method B): RT = 2,94, [M+H]+= 384,2.

Example 38:hydrochloride [3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine (compound 1039)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 194 mg) and N'-hydroxy-2-methylpropanamide (x = 24 h, y = 4 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. light yellow precipitate was filtered and dried in vacuum,getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) free amine δHby 8.22-8,35 (m, 1H), 7,87-of 7.97 (m, 1H), 7.68 per-of 7.82 (DD, 2H), 7,44-to 7.59 (m, 3H), with 4.64 (K, 1H), 3,45-3,66 (m, 1H), 3.04 from-3,19 (m, 1H), 2,88-3,03 (m, 1H), 2,34 (sh, 1H), 2,00-2,25 (m, 2H), 1.41 to 1,95 (m, 5H), to 1.37 (d, 3H), 1,19 (who, 6H).

Example 39:hydrochloride ((R)-1-naphthalene-1-retil)-{3-[3-(4-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclopentyl}amine (compound 1040)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 195 mg) and N'-hydroxy-(4-triptoreline)imitated (x = 24 h, y = 4 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. Colorless precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS (method B): RT = 3,21, [M+H]+= 452,1.

Example 40:hydrochloride [3-(3-methyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine (compound 1041)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 190 mg) and N'-hydroxyazetidine (x = 1 h, y = 20 h). Chromatography (PE-EtOAc 100:0 to 40:60) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. the Precipitate was filtered and dried in vacuum, obtaining specified in the header of the connection.1H NMR (300 MHz, DMSO) δH10,26 (s, 1H), to 9.45 (s, 1H), 8,31 (d, 1H), of 7.90-to 8.12 (m, 3H), 7,50-of 7.70 (m, 3H), 5,35 (K, 1H), 3,63-3,81 (m, 1H), 3,44-3,62 (m, 1H), 2,00 is 2.33 (m, 4H), 2,24 (s, 3H), 1,90 (s, 1H), 1,73 (d, 3H), 1,65-to 1.79 (m, 1H).

Example 41:{3[3-(5-methylthiazole-2-ylmethyl)-[1,2,4]oxadiazol-5-yl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine (compound 1042)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 190 mg) and N-hydroxy-2-(5-methylthiazole-2-yl)acetamide (x = 4 h, y = 20 h). Chromatography (PE-EtOAc 100:0 to 30:70, then CH2Cl2-MeOH 98:2 to 80:20) gave specified in the header connection. LC-MS (method B): RT = 2,68, [M+H]+= 419.

Example 42:hydrochloride ((R)-1-naphthalene-1-retil)-[3-(3-propyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]amine (compound 1043a and 1043b)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 190 mg) and N'-hydroxybutylidene (x = 4 h, y = 20 h). Chromatography (PE-EtOAc 100:0 to 30:70) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding EtzO. the Precipitate was filtered and dried in vacuum, obtaining mentioned in the title compound as 2-isomer.13C NMR (75.5 MHz, DMSO) major isomer δ: 183,03, 170,02, 142,44, 133,85, 131,34, 129,01, 126,95, 126,09, 125,98, 125,62, 123,35, 56,50, 51,48, 37,54, 34,81, 33,20, 29,43, 27,43, 24,64, 20,10, 13,74.

Example 43:hydrochloride of 1-{5-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]-[1,2,4]oxadiazol-3-ylmethyl}-1H-pyridine-2-she (connection 1044)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (prepared is e 3, 190 mg) and N~hydroxy-2-(2-oxo-2H-pyridin-1-yl)acetamide (x = 5 h, y = 19 h). Chromatography (PE-EtOAc 60:40 to 0:100, then CHCl3-MeOH 100:0 to 90:10) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. the Precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS (method B): RT = 2,23, [M+H]+= of 415.3.

Example 44:hydrochloride {3-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine (compound 1045)

Followed General procedure C using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 190 mg) and N'-hydroxy-(4-methoxyphenyl)imitated (x = 4 h, y = 20 h). Chromatography (PE-EtOAc 100:0 to 30:70, then CH2Cl2-MeOH 90:10 to 70:30) gave an oil which was treated with 4 N. HCl in dioxane. Deposition occurred when adding Et2O. the Precipitate was filtered and dried in vacuum, obtaining specified in the header connection. LC-MS (method B): RT = 3,11, [M+H]+= 414,1.

Example 45:amide 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarboxylic acid (compound 1046)

Followed the General procedure using 3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (preparation 3, 155 mg) and aq. NH3(2.5 ml). Chromatography (CH2Cl2-MeOH 90:10 to 70:30) gave specified in which the head connection. LC-MS (method B): RT=1,93, [M+H]+= 283,2.

Example 46:4-methyl-N-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl]benzosulfimide (connection 1047a, the connection 1047b, the connection 1047c and connection 1047d)

To a stirred mixture of 3-oxocyclopentanecarboxylate acid (1.2 g) and NEt3(1,56 ml) in THF (50 ml) in an argon atmosphere was added dropwise 4-methylbenzenesulfonate (1,71 ml). Stirring is continued at K.T. for 1 h before adding N,N'-dimethyl-1,3-propandiamine. Stirring is continued at K.T. within 10 minutes the Mixture was diluted with EtOAc, washed with aqueous HCl (1 M) and saturated salt solution, dried over Na2SO4, filtered and concentrated in vacuum, obtaining 4-methyl-N-(3-oxocyclopentanecarboxylate)benzosulfimide (connection 1113), used without further purification. Followed General procedure A, using 4-methyl-N-(3-oxocyclopentanecarboxylate)benzosulfimide (1,9 g) and (+)-(R)-1-naphthalene-1-ylethylamine when the reaction time to 4 h the Mixture was diluted with CH2Cl2, washed with saturated aqueous NaHCO3and saturated salt solution, dried over Na2SO4, filtered and concentrated in vacuo,getting a yellow foam. The foam was treated with hot EtOH. The precipitate formed after cooling was filtered off, washed with EtOH, receiving specified in the header joint is in the form of a white powder. LC-MS (method B): RT (4 isomer) = 3,02, 3,10, 3,37, 4,10, [M+H]+= 437,4, [M-H]-= 435,4.

Example 47:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (connection 1048/1049/1050)

Followed General procedure A, using 3-(4-cyanophenyl)cyclohexanone (5 g) and (+)-(R)-1-naphthalene-1-ylethylamine (3,7 ml). Chromatography (heptane-EtOAc 100:0 to 0:100) gave specified in the title compound in the form of a solid substance (fraction A)specified in the title compound as oil (fraction B) and specified in the title compound as oil (fraction C). Fractions A and B contain a single diastereomers: compound 1048 and the connection 1049, respectively. Fraction C contained a mixture of 2 diastereomers: compound 1050. Connection 104813C NMR (75.5 MHz, DMSO) δ: 153,24, 142,40, 133,48, 132,00, 130,84, 128,62, 127,76, 126,46, 125,64, 125,55, 125,17, 123,07, 122,97, 118,92, 108,37, 51,09, 50,03, 38,25, 37,30, 32,69, 28,86, 24,59, 20,15. Connection 104913C NMR (75.5 MHz, DMSO) δ: 153,25, 142,12, 133,43, 132,09, 130,87, 128,60, 127,96, 126,46, 125,67, 125,54, 125,17, 122,97, 122,85, 118,97, 108,42, 50,17, 49,28, 37,07, 36,17, 32,84, 30,61, 24,38, 20,39. Connection 1050 (2 isomer ca. 2:1)13C NMR (75 MHz, DMSO) δ: 152,65, 152,58, 142,13, 141,99, 133,46, 133,44, 132,20, 130,79, 130,76, 128,61, 128,59, 127,80, 126,50, 125,71, 125,67, 125,60, 125,19, 122,94, 122,87, 122,83, 122,72, 118,92, 108,65, 108,63, 53,79, 53,62, 49,30, 49,16, 42,67, 42,41, 40,71, 39,96, 33,25, 33,07, 32,15, 24,74, 24,49, 24,33.

General procedure E

To a solution of the nitrile (1 EQ.) in EtOH (0,12 M) was added K2CO3(12 EQ.) and hydrochloride hydrox lamina (7 EQ.). The mixture is stirred at the boiling point with the return of phlegmy during the night. After filtration of the precipitate on the filter was extracted with hot EtOH. The combined extracts were concentrated in vacuum.If necessary, the purification was performed by flash chromatography with a continuous gradient.

Example 48:N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1051)

Followed General procedure E using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction A, 500 mg) and hydroxylamine hydrochloride. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:80:20) gave specified in the title compound as a colourless solid.13C NMR (75.5 MHz, DMSO) δ: 150,76, 148,10, 142,43, 133,47, 130,84, 130,69, 128,60, 126,42, 126,25, 125,61, 125,55, 125,16, 123,09, 122,96, 51,01, 50,14, 38,72, 36,78, 33,14, 29,04, 24,59, 20,30.

Example 49:N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1052)

Followed General procedure E using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction B, 500 mg) and hydroxylamine hydrochloride. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:50:50) gave specified in the title compound as a yellow oil.13C NMR (75.5 MHz, DMSO) δ: 167,78, 150,81, 148,11, 142,13, 133,43, 130,86, 130,81, 128,60, 127,44, 126,44, 125,66, 125,54, 125,29, 125,15, 122,99, 122,83, 50,19, 49,38, 36,58, 33,38, 3078, 24,42, 20,55.

Example 50:N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1053a and connection 1053b)

Followed General procedure E using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction C, 100 mg) and hydroxylamine hydrochloride. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:90:10) gave specified in the header of the connection.13C NMR (75.5 MHz, DMSO) δ: 168,18, 151,20, 151,20, 148,10, 148,04, 142,76, 142,66, 133,88, 131,42, 131,23, 129,04, 127,94, 126,87, 126,71, 126,04, 125,77, 125,60, 123,32, 123,24, 123,17, 54,37, 54,23, 49,65, 42,88, 42,61, 41,83, 40,98, 34,04, 32,83, 25,33, 25,09, 24,88 (2 isomer in almost equal amounts).

Example 51:{3-[4-(aminopyrrolidine-1-ylmethyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1054)

To a solution of 4-[3-(R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction A, 150 mg) in MeOH (1.5 ml) in an argon atmosphere was added N-acetylcysteine (7 EQ.) and pyrrolidine (7.4 equiv.). The mixture was stirred at 70°C for 4 days. MeoH was removed inthe vacuum.The residue was taken into water and was extracted with CH2Cl2(4 times). The combined extracts were concentrated in vacuumand purified by flash chromatography with a continuous gradient (CH2Cl2-MeOH 100:0 to 50:50), receiving specified in the header connection. LC-MS (method B): RT = 2,01, [M+H]+= 426,3.

Example 52:4-[3-((R)-1-naphthalene-1-jatila is Ino)cyclohexyl]benzamide (connection 1055)

To a solution of N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamidine (for example, 48, 200 mg) in EtOAc (10 ml) was added SnCl2.2H2O (3 EQ.) The mixture is stirred at the boiling point with the return of phlegmy during the night. After cooling to K.T. mixture was diluted with EtOAc and washed with aqueous saturated NaHCO3. The organic phase was subjected to chromatography (PE-EtOAc 100:0 to 0:100 to EtOAc-MeOH 90:10), receiving specified in the header connection. LC-MS (method B): RT = 1,92, [M+H]+= 372,3.

General procedure F

To a solution of benzonitrile in MeOH (0,09 M, y ml) was added 28% aq. NaOH (y/2 ml). The mixture was heated to the boil with the return of phlegmy during the night. MeOH was removed under reduced pressure. The residue was taken in water and was added 4 n aq. HCl to pH=5. The precipitate was collected, washed with water and dried in vacuum.

Example 53:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056)

Followed General procedure F using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction A, 3.5 g), getting the corresponding acid.13C NMR (75.5 MHz, DMSO) δ: 167,33, 152,18, 142,11, 133,49, 130,83, 129,16, 128,72, 128,62, 126,66, 126,54, 125,68, 125,57, 125,20, 123,19, 122,96, 51,12, 50,24, 38,38, 37,04, 32,81, 28,90, 24,45, 20,22.

Example 54:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1057)

Followed General procedure F using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction B, 0.8 g)to give the corresponding acid.13C NMR (75.5 MHz, DMSO) δ: 167,27, 151,71, 140,47, 133,43, 130,73, 129,26, 128,68, 128,54, 126,93, 126,85, 125,96, 125,55, 125,36, 123,33, 122,71, 50,10, 49,71, 36,63, 35,45, 32,55, 30,15, 23,72, 20,29.

Example 55:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1058)

Followed General procedure F using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzonitrile (47, fraction C, 1.0 g)to give the corresponding acid.13C NMR (75 MHz, DMSO) δ: 167,37, 150,91, 150,88, 133,37, 130,44, 130,38, 129,39, 129,36, 129,34, 128,73, 128,70, 127,42, 127,38, 126,63, 126,58, 126,24, 126,14, 125,55, 125,51, 123,58, 123,48, 122,65, 122,57, 53,96, 53,79, 49,04, 48,95, 42,04, 41,89, 38,71, 38,19, 32,87, 31,30, 30,20, 24,32, 24,11, 22,72.

Example 55a:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1058a)

1H NMR (300 MHz, DMSO) δ scored 8.38-8,21 (m, 1H), 7.95 is-7,87 (m, 1H), 7,82 (d, 2H), of 7.75 (DD, 2H), EUR 7.57-7,39 (m, 3H), 7,30 (m, 2H), 4.72 in (DD, 1H), 3,17-of 3.06 (m, 1H), 2,82 (m, 1H), 1,91 by 1.68 (m, 3H), 1,66-of 1.27 (m, 8H).

Example 56:ethyl ester of 3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1059)

Followed General procedure, But using the ethyl ester 3-(3-oxocyclohexyl)benzoic acid (10 g) and (+)-(R)-1-naphthalene-1-ylethylamine (6 ml). Chromatography (heptan-EtOAc 100:0 to 0:100) gave specified in the title compound as a mixture of isomers. LC-MS (method B): RT = 2,81, [M+H]+= 402,2.

Example 57:N-(2-hydroxyethyl)3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1060)

To a solution of ester ethyl 3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (Sp. 56, 2.15 g) in anhydrous MeCN (25 ml) in an argon atmosphere was added ethanolamine (15 EQ.) and K2CO3. The mixture is stirred at the boiling point with the return of phlegmy within 2 days. MeCN was removed in vacuo.The residue was taken in EtOAc, washed with water, dried over MgSO4, filtered and concentrated inthe vacuum.Chromatography (PE-EtOAc-MeOH 10:90:0 to 0:100:0 to 0:80:20) gave specified in the header connection. LC-MS (method B): RT = 2,13, [M+H]+= 417,2, [M-H]-= 415,4.

Example 58:3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1061/1062)

To a solution of ester ethyl 3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (10.4 g) in MeOH (200 ml) was added 2 n aq. NaOH (100 ml). The solution was stirred at K.T. overnight and concentrated in vacuo.The residue was taken in water (150 ml) and 4 n aq. HCl (ca 50 ml) was added dropwise until pH=7 and the precipitate was retained. The acid was filtered, washed with water and dried in vacuum,getting listed in the title compound as a mixture of isomers. 100 mg purified the reparative chiral HPLC, getting listed in the title compound (fraction A, the connection 1061) and indicated in the title compound (fraction B, the connection 1062), each as a single isomer. Preparative chiral HPLC was performed on a column Chiralpak AD-H 250×10 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with a mixture of n-heptane:2-propanol:NEt3:CH3COOH(85:15:0,1:0,1); flow rate = 3.0 ml/min

Connection 1061: RT=13,4 min;13C NMR (75.5 MHz, DMSO) δ: 168,11, 147,83, 141,93, 133,86, 131,89, 131,45, 131,24, 129,06, 128,72, 128,00, 127,11, 127,08, 126,20, 125,97, 125,66, 123,55, 123,22, 50,71, 50,07, 37,01, 36,83, 33,62, 30,81, 24,56, 20,89. Connection 1062: RT=at 15.3 min;13C NMR (75.5 MHz, DMSO) δ:
168,58, 147,67, 142,50, 133,89, 133,22, 131,30, 130,75, 129,05, 128,39, 127,86, 127,01, 126,94, 126,11 , 125,99, 125,60, 123,47, 123,31, 51,04, 50,29, 39,23, 37,31, 33,60, 29,15, 24,80, 20,68.

Example 59:((R)-1-naphthalene-1-retil)-(3(S)-phenylcyclohexyl)amine (compound 1063)

Followed General procedure A, using (S)-3-phenylcyclohexanone (100 mg) and (R)-(+)-1-naphthalene-1-ylethylamine. Chromatography (heptane-EtOAc 85:15 to 0:100) gave specified in the header connection. LC-MS (method B): RT = 2,42, [M+H]+= 330,3.

Example 60:((R)-1-naphthalene-1-retil)-(3(R)-phenylcyclohexyl)amine (compound 1064)

Followed General procedure, But using (R)-3-phenylcyclohexanone (100 mg) and (R)-(+)-1-naphthalene-1-ylethylamine. Chromatography (heptane-EtOAc 90:10 to 0:100) gave specified in the title compound LC-MS (method B): RT = 2,31, [M+H]+= 330,3.

General procedure G

To a mixture of amine (1 EQ.), cyclol-2-EN-1-she (1.2 EQ.) and PEG2000 (4 g 10 mmol amine) at 60°C was added RuCl3(3%). The mixture was stirred at 60°C over night. After cooling to K.T.) was added Et2O (20 ml, 10 mmol). The mixture was kept in the refrigerator for 30 minutes before filtering the precipitate. The solid was extracted with Et2O (3 times). The combined extracts were washed with water, dried over Na2SO4, filtered and concentrated in vacuo.If necessary, the purification was performed by flash chromatography with a continuous gradient.

Example 61:N-((R)-1-naphthalene-1-retil)-N'-phenylcyclohexane-l,3-diamine (compound 1065)

Followed General procedure G, using aniline (0,91 ml) and cyclohex-2-EN-1-it. Chromatography (CH2Cl2-MeOH 100:0 to 85:15) gave 3-phenylaminopyrimidine.

Followed the procedure But using 3-phenylaminopyrimidine (41 mg) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:90:10) gave specified in the title compound in the form of a mixture of 2 isomers in a ratio of 1:3.13C NMR (75.5 MHz, DMSO) δ: 147,94, 142,31, 133,44, 130,77, 128,76, 128,65, 128,58, 126,37, 125,62, 125,59, 125,52, 125,12, 122,93, 122,83, 115,01, 114,88, 112,20, 50,22, 49,80, 49,59, 49,38, 46,15, 46,01, 37,77, 36,15, 31,78, 31,71, 29,97, 24,51, 24,34, 19,60, 19,26.

Example 62:N-((R)-1-naphthalene-1-retil)-N'-(3-triptoreline)C is clohexane-l,3-diamine (compound 1066)

Followed General procedure G using 3-triptorelin (1,61 g) and cyclohex-2-EN-1-it. Chromatography (PE-EtOAc 100:0 to 0:100) gave 3-(3-triptoreline)aminocyclohexane (connection 1114).

Followed the procedure But using 3-(3-triptoreline)aminocyclohexane (125 mg) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:90:10) gave specified in the header connection. LC-MS (method B): RT = 2,94, [M+H]+= 413,2.

Example 63:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexylamino]benzonitrile (connection 1067)

Followed General procedure G using 4-aminobenzonitrile (1.18 g) and cyclohex-2-EN-1-it. Chromatography (PE-EtOAc 100:0 to 0:100) gave 4-(3-oxocyclohexyl)benzonitrile.

Followed the procedure a using 4-(3-oxocyclohexyl)benzonitrile (145 mg) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:90:10) gave specified in the header connection. LC-MS (method B): RT = 2,56, [M+H]+= 370,2.

Example 64:(3-morpholine-4-illlogical)-((R)-1-naphthalene-1-retil)amine (compound 1068)

To a stirred mixture of the research (3,7 ml) and cyclohex-2-EN-1-she (3.4 ml) in water (50 ml) was added Cu(OAc)2.H2O (350 mg). The mixture was stirred at K.T. for 15 h and was filtered. The filtrate was extracted with EtOAc. Together the data extracts were washed with water and saturated salt solution, dried over Na2SO4, filtered and concentrated in vacuum, obtaining a mixture of 1:1 cyclohex-2-EN-1-it 3-morpholine-4-illlogical used without further purification.

Followed General procedure A, using 3-morpholine-4-illlogical (1 g, 50% purity, 5.4 mmol) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (EtOAc) gave specified in the title compound in the form of temnerature oil (mixture of 2 isomers of ca 1:1).13C NMR (75.5 MHz, DMSO) δ: 142,28, 142,05, 133,47, 133,39, 130,92, 130,86, 128,58, 126,42, 126,38, 125,61, 125,57, 125,51, 125,45, 125,12, 123,21, 123,07, 122,97, 122,72, 66,41, 66,30, 57,86, 57,78, 50,54, 49,54, 49,45, 49,35, 49,19, 48,46, 34,44, 32,62, 30,84, 27,75, 27,64, 24,43, 19,68, 19,48.

Example 65:((R)-1-naphthalene-1-retil)-(3-pyridin-2-illlogical)amine (compound 1069/1070)

Followed General procedure A, using 3-(2-pyridinyl)cyclohexanone (1 g) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:85:15) gave specified in the title compound in the form of a mixture of 2 isomers (fraction A, the connection 1069) and specified in the title compound in the form of a mixture of 2 isomers (fraction B, the connection 1070) in the ratio of 1:1. Connection 1069, main isomer13C NMR (75.5 MHz, DMSO) δ: 165,48, 148,61, 142,04, 136,19, 133,47, 130,90, 128,62, 126,49, 125,69, 125,56, 125,18, 123,02, 122,93, 121,17, 120,95, 50,37, 49,48, 39,02, 37,25, 31,80, 28,94, 24,35, 20,03. Connection 107013C NMR (75.5 MHz, DMSO) δ: 165,47, 165,39, 149,12, 142,64, 142,57, 136,83, 133,90, 133,88, 131,23, 129,02, 126,89, 126,08, 126,04, 125,60, 123,38,123,33, 123,24, 123,18, 121,61, 121,46, 121,40, 54,20, 54,06, 49,80, 49,62, 45,16, 44,86, 34,01, 32,86, 32,52, 32,45, 25,16, 24,86, 24,81.

Example 66:ethyl ester 5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]thiophene-2-carboxylic acid (compound 1071)

Followed General procedure, But using the ethyl ester 5-(3-oxocyclohexyl)thiophene-2-carboxylic acid (1 g) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:90:10) gave specified in the title compound in the form of a mixture of 3 isomers (fraction A) and 0.9 g specified in the title compounds as a mixture of 3 isomers (fraction B). LC-MS (method B): RT = 2,98, [M+H]* = 408,2.

Example 67:5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]thiophene-2-carboxylic acid (compound 1072)

To a solution of ester ethyl 5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]thiophene-2-carboxylic acid (fraction A 0.6 g) in MeOH (30 ml) and water (10 ml) was added LiOH (5 EQ.). The solution was stirred at the boiling point with the return of phlegmy within 2 hours MeOH was removed in vacuumand added 4 N. aqueous HCl until there was sludge. The solid was filtered, washed with water and dried in vacuum, obtaining specified in the header of the connection.13C NMR (150,9 MHz, DMSO) δ: Main isomer: 163,41, 157,15, 140,77, 140,77, 133,43, 131,63, 130,71, 128,67, 126,84, 125,88, 125,54, 125,32, 123,38, 123,21, 122,76, 50,23, 49,74, 38,46, 33,49, 33,43, 28,64, 23,83, 19,87

Example 68:ethyl ester 5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carboxylic acid (compound 1073)

Followed General procedure, But using the ethyl ester 5-(3-oxocyclohexyl)furan-2-carboxylic acid (1 g) and (+)-(R)-1-naphthalene-1-ylethylamine. Chromatography (PE-EtOAc-MeOH 100:0:0 to 0:100:0 to 0:90:10) gave specified in the header connection. LC-MS (method B): RT = 2,85, [M+H]+= 392,3.

Example 69:5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carboxylic acid (compound 1074a, the connection 1074b and connection 1074c)

To a solution of ester ethyl 5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carboxylic acid (1.4 g) in MeOH (75 ml) and water (25 ml) was added LiOH (5 EQ.). The solution was stirred at the boiling point with the return of phlegmy within 2 hours MeOH was removed in vacuo and added 4 N. aqueous HCl until acidic pH. The compound was extracted with EtOAc. The combined extracts were dried over MgSO4, filtered and concentrated in vacuum, obtaining specified in the title compound in the form of not-quite-white solid. 3 isomer13C NMR (150,9 MHz, DMSO) δ: 162,64, 162,55, 162,15, 160,16, 160,10, 159,94, 145,27, 144,84, 144,79, 133,40, 130,69, 130,63, 130,49, 130,46, 128,74, 128,70, 128,67, 127,34, 127,29, 126,99, 126,89, 126,20, 126,14, 126,02, 125,95, 125,63, 125,58, 125,51, 125,38, 125,34, 123,40, 123,29, 123,14, 122,74, 122,71, 122,62, 117,11, 116,96, 116,82, 106,11, 106,07, 15,59, 105,56, 53,25, 52,95, 49,83, 49,66, 49,32, 49,16, 36,00, 35,56, 35,43, 34,98, 33,02, 31,64, 31,49, 31,40, 30,51, 30,35, 30,15, 29,60, 28,73, 23,70, 23,57, 23,47, 22,93, 22,87, 20,00, 19,68.

General procedure H

To the solution or suspension of the acid (1 EQ.) in DMF (1 M) in an argon atmosphere was added HOBt (1.2 EQ.), EDAC (1.3 EQ.), 4 methylmorpholine (2 EQ.) and N-hydroxyamides (1.2 EQ.). The mixture was stirred at K.T. during the night. CDI (1.1 EQ.) was added and the mixture was subjected to microwave irradiation (10 min, 150°C). The mixture was cooled to K.T., added EtOAc, washed with water and saturated salt solution, dried over Na2SO4, filtered and concentrated in vacuo.If necessary, the purification was performed by flash chromatography with a continuous gradient.

Preparation 4:3-((R)-1-naphthalene-1-ylethylamine)cyclohexanecarbonyl acid

To a solution of 3-oxo-1-cyclohexanecarboxylic acid (1.8 g) in 1,2-dichloroethane (60 ml) was added (+)-(R)-1-naphthalene-1-ylethylamine (2.2 g), glacial AcOH (1 EQ., 0.75 ml) and NaBH(OAc)3(1.5 EQ., 4.1 g). The mixture was stirred at K.T. within 48 h before removing the solvent. The residue was treated with 1 N. NaOH (ca 100 ml) and the pH was brought to 7 by addition of 4 N. HCl. The mixture brought to a boil with the return of phlegmy. The solid obtained upon cooling, was filtered and washed with boiling EtOH, getting mentioned in the title compound in the form of fine powder. The filtrate was concentrated inthe vacuum. OST the current was dissolved in hot MeCN and a small amount of MeOH. The solid obtained upon cooling, was filtered and washed with MeCN, getting listed at the beginning of the connection.

Example 70:{3-[3-(4-forfinal)-[1,2,4]oxadiazol-5-yl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1075)

Followed General procedure N, using 3-((R)-1-naphthalene-1-ylethylamine)cyclohexanecarbonyl acid (preparation 4, 110 mg) and 4-fluoro-N-hydroxybenzamide. Chromatography (PE-EtOAc 100:0 to 0:100) gave specified in the header of the connection.13C NMR (75.5 MHz, DMSO) δ: 183,55, 166,86, 164,24 (1JCF=249,1 Hz), 142,45, 133,92, 131,30, 129,87, 129,75, 129,06, 126,91, 126,05 (3JCF=9.8 Hz), 125,60, 123,31, 123,28, 116,68 (2JCF=21,9 Hz), 50,33, 49,29, 35,45, 31,69, 30,00, 29,29, 24,78, 20,24.

Example 71:((R)-1-naphthalene-1-retil)-{3-[3-(4-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclohexyl}amine (compound 1076)

Followed General procedure N, using 3-((R)-1-naphthalene-1-ylethylamine)cyclohexanecarbonyl acid (preparation 4, 110 mg) and 4-trifluoromethyl-N-hydroxybenzamide. Chromatography (PE-EtOAc 100:0 to 40:60) gave specified in the header connection. LC-MS (method B): RT = 3,23, [M+H]+= 466,2.

Example 72:((R)-1-naphthalene-1-retil)-[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclohexyl]amine (compound 1077)

Followed General procedure N, using 3-((R)-1-naphthalene-1-ylethylamine)C is clarexanyone acid (preparation 4, 110 mg) and N-hydroxybenzamide. Chromatography (PE-EtOAc 100:0 to 40:60) gave specified in the header connection. LC-MS (method B): RT = 2,93, [M+H]+= 398,2.

Example 73:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1078)

To a solution of 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (Sp. 53, 1.1 g) in DMF (40 ml) was added CDI (0.6 g). The mixture was stirred at K.T. within 2 h before the addition of aq. NH3(8 ml). The mixture was stirred at K.T. during the night. Added Et2O and water. After extraction the organic phase is washed with water and saturated salt solution, dried over MgSO4, filtered and concentrated in vacuum, obtaining mentioned in the title compound in the form of foam. LC-MS (method B): RT = 2,46, [M+H]+= 373,3.

Example 74:N-benzyloxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1079)

Followed General procedure B, using 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (Sp. 53, 0.27 mmol) and the hydrochloride of O-benzylhydroxylamine. Chromatography (PE-EtOAc 50:50 to 33:67) gave specified in the header connection. LC-MS (method B): RT = 3,03, [M+H]+= 479,4.

Example 75:4-itfinally ester 4-[3-((R)-1-naphthalene~1 ylethylamine)cyclohexyl]benzoic acid (compound 1080)

To dissolve the 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (Sp. 53, 0.4 g) in DMF (10 ml) was added CDI (0.21 g, 1.2 EQ.). The solution was stirred at K.T. for 1 h before addition of 4-itfinal (0.33 g, 1.4 EQ.) and K2CO3(1.5 EQ.). Stirring is continued at K.T. within 2 hours was Added water and the compound was extracted with EtOAc. The organic phase is washed with water (3 times) and saturated salt solution, was concentrated in vacuumand purified by chromatography (heptane-EtOAc 100:0 to 60:40), receiving specified in the title compound in the form of oil. LC-MS (method B): RT = 4,15, [M+H]+= 576,3.

General procedure I

To a solution of 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (Sp. 53, 1.6 g) in DMF (16 ml) was added CDI (0,83 g). The solution was stirred at K.T. over 4.5 h, 0.3 ml of this solution was added to the amine (2 EQ.). If the amine was prepared as the hydrochloride, was added DIPEA (1 EQ.). The mixture was which when K.T. for 3 days, filtered and purified preparative HPLC-MS (re-analyzed by LC/MS method A).

Example 76:2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}econsultancy acid (compound 1081)

Followed General procedure I, using 2-aminoethanesulfonic acid.1H NMR (600 MHz, DMSO) δH8,86 (sh, 2H), 8,44 (t, 1H), 8.34 per (d, 1H), 7,92-8,07 (m, 2H), 7,80-of 7.90 (m, 1H), 7,68 (d, 2H), 7,54-7,66 (m, 3H), 7,22 (d, 2H), 5,47 (sh, 1H), 3,52 (m, 2H), 3,13 is 3.23 (m, 1H), 3,02-3,11 (m, 1H), 2,68 (t, 2H), 1,73-2,02 (m, 5H), 1,42-1,71 (m, 6H), LC-MS (method A): RT=4,14, [M+H]+=480,8, [M-H]-=478,7.

Example 77:N-((R)-1-hydroxymethylpropane)4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1082)

Followed General procedure I, using (R)-2-amino-1-butanol. LC-MS (method A): RT = 3,99, [M+H]+= 444,8.

Example 78:N-((S)-1-hydroxymethylpropane)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1083)

Followed General procedure I, using (S)-2-amino-1-butanol. LC-MS (method A): RT = 3,99, [M+H]+= 444,8.

Example 79:N-(2-cyanoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1084)

Followed General procedure I, using 2-cyanoethylene. LC-MS (method A): RT = 4,01, [M+H]+= 426,4.

Example 80:N-(2-morpholine-4-retil)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1085)

Followed General procedure I, using 2-morpholine-4-ylethylamine. LC-MS (method A): RT = 3,49, [M+H]+= 486,1.

Example 81:N-(2-foradil)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1086)

Followed General procedure I using the hydrochloride of 2-foretelling. LC-MS (method A): RT = 4,04, [M+H]+= 418,8.

Example 82:N-(2,2-dottorati)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]be same (connection 1087)

Followed General procedure I, using 2,2-differetiation. LC-MS (method A): RT = 4,16, [M+H]+= 437,1.

Example 83:methyl ester 3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1088)

Followed General procedure I using the hydrochloride of the methyl ether complex 3-aminopropionic acid.13C NMR (151 MHz, DMSO) δ 171,72, 166,11, 163,16, 150,02, 133,46, 131,78, 130,69, 128,73, 127,08, 126,45, 126,03, 125,57, 125,46, 123,49, 122,81, 51,32, 50,90, 50,69, 37,20, 36,63, 35,36, 33,53, 32,48, 28,18, 23,59, 20,01, LC-MS (method A): RT = 4,07, [M+H]+=459,0.

Example 84:N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-pyridin-4-ylmethylene (connection 1089)

Followed General procedure I, using methylpyridin-4-ylmethylamino. LC-MS (method A): RT = 3,64, [M+H]+= 477,9.

Example 85:N-(2-dimethylaminoethyl)-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1090)

Followed General procedure I, using N,N,N'-trimethylethylenediamine. LC-MS (method A): RT = 3,49, [M+H]+= 458,2, [M-H]-= 456,0.

Example 86:(2-hydroxyethylpyrrolidine-1-yl)-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1091)

Followed General procedure I, using (S)-pyrrolidin-2-ilmeteo is. LC-MS (method A): RT = 3,99, [M+H]+= 456,8.

Example 87:N-(2-acetylamino)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1092)

Followed General procedure I, using N-(2-amino-ethyl)ndimethylacetamide. LC-MS (method A): RT = 3,86, [M+H]+= 458,2.

Example 88:N-ethyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1093)

Followed General procedure I, using ethylamine hydrochloride. LC-MS (method A): RT = 3,97, [M+H]+= 400,8.

Example 89:N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1094)

Followed General procedure I, using 2-hydroxyethylamine. LC-MS (method A): RT = 3,82, [M + H]+= 417,4.

Example 90:N-(2-hydroxy-1-hydroxymethyl-1-methylethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1095)

Followed General procedure I, using 2-amino-2-methylpropan-1,3-diol. LC-MS (method A): RT = 3,86, [M+H]+= are 460.9.

Example 91:N-(2-methoxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1096)

Followed General procedure I, using 2-methoxyethylamine. LC-MS (method A): RT = 3,99, [M+H]+= 430,8.

Example 92:N-(2-mercaptoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benthami the connection 1097)

Followed General procedure I, using 2-mercaptoethylamine. LC-MS (method A): RT = 4,11, [M+H]+=432,0.

Example 93:ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}acetic acid (compound 1098)

Followed General procedure I using the hydrochloride of ethyl ether complex aminouksusnoy acid.1H NMR (600 MHz, DMSO) δ 8,80 (t, 1H), 8,35 (d, 1H), to 7.93 (d, 1H), to 7.77 (DD, 2H), of 7.70 (d, 2H), 7,55-7,47 (m, 3H), 7,11 (d, 2H), 4,73 with 4.65 (m, 1H), 4,11 (K, 2H), 3.96 points (d, 2H), to 3.02 (t, 1H), 2,88 (s, 1H), 1,92-1,82 (m, 1H), 1,80 is 1.70 (m, 2H), 1,67-to 1.60 (m, 1H), 1,54 to 1.37 (m, 6H), 1,34-of 1.26 (m, 1H), 1,20 (t, 3H), LC-MS (method A): RT = 4,12, [M+H]+= 458,9

Example 94:N,N-dimethyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1099)

Followed General procedure I, using dimethylamine. LC-MS (method A): RT = was 4.02, [M+H]+= 400,8, [M-H]-= 399,3.

Example 95:N-(2-hydroxyethyl)-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1100)

Followed General procedure I, using 2-methylaminoethanol. LC-MS (method A): RT = a 3.87, [M+H]+= 431,4.

Example 96:N-ethyl-N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1101)

Followed General procedure I, using 2-ethylaminoethanol. LC-MS (im the A): RT = 3,96, [M+H]+= 444,9.

Example 97:N,N-bis-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene~1 ylethylamine)cyclohexyl]benzamide (connection 1102)

Followed General procedure I, using diethanolamine. LC-MS (method A): RT = 3,79, [M+H]+ =are 460.9.

Example 98:N-(2-dimethylaminoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1103)

Followed General procedure I, using N,N-(2-dimethylaminoethyl)amine. LC-MS (method A): RT = 3,47, [M+H]+= 444,2.

Example 99:N-(3-dimethylaminopropyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1104)

Followed General procedure I, using N,N-(3-dimethylaminopropyl)amine. LC-MS (method A): RT = 3,49, [M+H]+= 358,0.

Example 100:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}piperidine-1-ylmethanone (connection 1105)

Followed General procedure I, using piperidine. LC-MS (method A): RT = 4,27, [M+H]+ = 441,1.

Example 101:(4-methylpiperazin-1-yl)-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1106)

Followed General procedure I, using 4-methylpiperazin. LC-MS (method A): RT = 3.46 in, [M+H]+= 456,2, [M-H]-= 454,0.

Example 102:[4-(2-hydroxyethyl)piperazine-1-yl]-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}met the non (connection 1107)

Followed General procedure I, using 2-hydroxyethyl)piperazine. LC-MS (method A): RT = 3,44, [M+H]+= 486,1.

Example 103:morpholine-4-yl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1108)

Followed General procedure I, using morpholine. LC-MS (method A): RT = was 4.02, [M+H]+= 443,3.

Example 104:(4-hydroxypiperidine-1-yl)-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1109)

Followed General procedure I, using piperidine-4-ol. LC-MS (method A): RT = a 3.87, [M+H]+= 456,9.

Example 105:N-(3-imidazol-1-ylpropyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1110)

Followed General procedure I, using 3-imidazol-1-ylpropionic. LC-MS (method A): RT = 3,51, [M+H]+= 481,3.

General procedure J

To a solution/suspension of ester (6.5 mmol) in MeOH (30 ml) and water (10 ml) was added LiOH (5-8 EQ.). After stirring/stirring for 4 h the reaction mixture is slightly concentrated in vacuo and added water. The product precipitated with addition of 4 n aq. HCl under stirring until pH 5 (to obtain a neutral connection) or to pH 1-2 (to obtain the hydrochloride salt). Precipitation was collected by filtration. If precipitation did not occur, a mixture of extras who were garofali DCM, the organic extracts were concentrated in vacuo, the residue was dissolved in DMSO and/or DMF, and the product was purified preparative HPLC-MS, re-analyzed by LC/MS (method B).

Example 106:{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}acetic acid (compound 1115)

Followed General procedure J, using ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}acetic acid (compound 1098).13C NMR (151 MHz, DMSO) δ 171,29, 166,16, 149,98, 133,41, 131,32, 130,61, 128,71, 127,29, 127,14, 126,48, 126,10, 125,53, 125,49, 123,58, 122,72, 50,78, 41,12, 36,76, 36,50, 32,26, 27,88, 23,25, 19,91.

Example 107:4-tert-butyl ester, 1-methyl ester (S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid (compound 1116)

Followed General procedure I using the hydrochloride of 4-tert-butyl 1-methyl ether complex of 1-aspartic acid.13C NMR (151 MHz, DMSO) δ 171,28, 169,04, 165,91, 151,20, 142,43, 133,45, 130,89, 130,80, 128,58, 127,17, 126,49, 126,39, 125,60, 125,53, 125,14, 123,08, 122,95, 80,25, 52,04, 51,12, 50,16, 49,15, 38,54, 36,92, 36,81, 32,98, 28,95, 27,53, 24,62, 20,21.

Example 108:4-tert-butyl ester (S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid (compound 1117)

Followed General procedure J, using 4-tert-butyl complex is the ester 1-methyl ester 2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid (compound 1116). 13C NMR (151 MHz, DMSO) δ 172,79, 169,88, 165,42, 150,58, 141,95, 133,45, 131,72, 130,79, 128,61, 126,97, 126,54, 126,44, 125,68, 125,55, 125,20, 123,16, 122,91, 79,56, 51,01, 50,21, 50,18, 38,29, 37,80, 36,83, 32,89, 28,79, 27,59, 24,38, 20,18.

Example 109:methyl ester of (R)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenyl-propionic acid (compound 1118)

Followed General procedure I using the hydrochloride of the methyl complex ester of D-phenylalanine.13C NMR (151 MHz, DMSO) δ 172,14, 166,19, 151,07, 142,42, 137,65, 133,44, 130,94, 130,80, 128,93, 128,58, 128,11, 127,20, 126,41 (two overlapping signal), 126,34, 125,61, 125,53, 125,14, 123,07, 122,94, 54,07, 51,80, 51,06, 50,11, 38,56, 36,91, 36,07, 32,94, 28,93, 24,61, 20,20.

Example 110:(R)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid (compound 1119)

Followed General procedure J, using methyl ester 2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionic acid (compound 1118) and LiOH.13C NMR (151 MHz, DMSO) δ 172,53, 164,74, 150,30, 142,39, 139,34, 133,44, 132,53, 130,81, 129,40, 128,57, 127,47, 126,50, 126,46, 126,40, 125,60, 125,54, 125,43, 125,14, 123,06, 122,94, 55,49, 50,98, 50,05, 38,64, 37,00, 36,84, 32,94, 28,90, 24,57, 20,21.

Example 111:methyl ester (S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionic acid (compound 1120)

Followed General procedure I, using the UYa hydrochloride methyl ether complex 1-phenylalanine. 13C NMR (75 MHz, DMSO) δ 172,12, 166,17, 151,06, 142,33, 137,64, 133,45, 130,95, 130,80, 128,92, 128,58, 128,11, 127,20, 126,42, 126,34, 125,60, 125,52, 125,15, 123,09, 122,94, 54,06, 51,79, 51,07, 50,17, 38,43, 36,91, 36,09, 32,99, 28,94, 24,54, 20,20.

Example 112:hydrochloride (S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3~phenylpropionic acid (compound 1121)

Followed General procedure J, using methyl ester 2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionic acid (compound 1120).13C NMR (151 MHz, DMSO) δ 173,05, 165,96, 148,84, 138,22, 133,31, 131,49, 130,29, 129,35, 128,96, 128,84, 128,18, 128,01, 127,29, 126,71, 126,42, 126,16, 125,85, 125,48, 124,57, 122,39, 54,14, 51,40, 50,43, 36,28, 36,11, 35,86, 31,35, 26,28, 21,73, 19,47.

Example 113:methyl ester (S)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1122)

Followed General procedure I using the hydrochloride of the methyl ether complex of L-tryptophan.13C NMR (151 MHz, DMSO) δ 172,49, 166,18, 151,06, 142,42, 135,97, 133,44, 130,98, 130,80, 128,58, 127,24, 126,94, 126,39, 125,60, 125,53, 125,14, 123,50, 123,07, 122,94, 120,86, 118,30, 117,88, 111,35, 109,88, 53,60, 51,76, 51,08, 50,14, 38,50, 36,92, 33,02, 28,93, 26,48, 24,60, 20,20.

Example 114:(S)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1123)

Followed General procedure J, using metrov the th ester 3-(1H-indol-3-yl)-2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1122). 13C NMR (151 MHz, DMSO) δ 172,45, 164,74, 150,15, 142,39, 135,66, 133,44, 132,79, 130,80, 128,58, 128,18, 127,24, 126,50, 126,38, 125,59, 125,54, 125,13, 123,15, 123,07, 122,94, 120,16, 118,67, 117,60, 111,57, 110,77, 55,29, 51,02, 50,09, 38,58, 36,83, 33,00, 28,92, 27,07, 24,57, 20,21.

Example 115:methyl ester of (R)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1124)

Followed General procedure I using the hydrochloride of the methyl ether complex D-tryptophan.13C NMR (151 MHz, DMSO) δ 172,48, 166,21, 151,04, 142,41, 135,98, 133,44, 130,99, 130,80, 128,58, 127,24, 126,95, 126,38, 125,60, 125,53, 125,14, 123,50, 123,07, 122,94, 120,86, 118,30, 117,89, 111,35, 109,90, 53,63, 51,76, 51,07, 50,12, 38,55, 36,91, 32,97, 28,93, 26,48, 24,60, 20,21.

Example 116:(R)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1125)

Followed General procedure J, using methyl ester of 3-(1H-indol-3-yl)-2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1124).13C NMR (151 MHz, DMSO) δ 172,04, 165,45, 150,47, 142,31, 135,83, 133,44, 132,05, 130,80, 128,58, 127,60, 126,86, 126,42, 126,35, 125,61, 125,53, 125,14, 123,24, 123,07, 122,93, 120,49, 118,33, 117,92, 111,04, 54,47, 50,95, 50,08, 38,54, 36,84, 32,96, 28,87, 26,88, 24,54, 20,20.

General procedure I-1:

To a solution of 4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056, 35 mg) in DMF (1 ml) was added HATU (1.2 EQ.) and DIPEA (2 EQ.). Solution re exively when K.T. within 2 h, then added to the amine (2 EQ.). If the amine was prepared as the hydrochloride, was added DIPEA (2 EQ.). The mixture was which when K.T. overnight, was filtered and was purified preparative HPLC-MS (re-analyzed by LC/MS method A).

General procedure I-2:

A similar procedure I, except that the compound 1057 (Example 54) is used instead of the compound 1056.

General procedure I-3

To the solution or suspension of 4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056) in DMF (1 M) in an argon atmosphere was added HOBt (1.1 equiv.) EDAC (1 EQ.), 4 methylmorpholin (1 EQ.) and amine (1 EQ.). The mixture was stirred at K.T. during the night. DMF was removed in vacuo and purification was performed by flash chromatography with a continuous gradient.

Example 117:ethyl ester (cyclohexyl-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1126).

Followed General procedure I-2, using ethyl ester of N-cyclohexylglycine.1H NMR (500 MHz, DMSO, T=400 K) δ 8,31 (d, 1H), 7,87 (d, 1H), 7,74 (d, 1H), 7,69 (d, 1H), 7,50-7,42 (m, 3H), 7,20 (DD, 4H), 4,81-of 4.67 (m, 1H), 4.09 to (K, 2H), 3,99 (s, 2H), 3,76-3,63 (m, 1H), is 3.08 (t, 1H), 2,97-2,87 (m, 1H), 1,90 of-1.83 (m, 1H), 1,81-to 1.67 (m, 6H), 1,65 to 1.37 (m, 11H), of 1.18 (t, 3H), 1,14-of 1.02 (m, 3H), LC-MS (method A): RT=5,47, [M+H]+=to 541.3.

Example 118:diethyl ester 2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohex the Il]benzoylamine}malonic acid (compound 1127)

Followed General procedure I-2, using the hydrochloride of diethyl aminomalonate.1H NMR (500 MHz, DMSO) δ to 8.45 (s, 1H), 8,28 (d, 1H), of 7.90 (d, 1H), 7,79 (d, 1H), 7,76-of 7.69 (m, 3H), 7,55-7,44 (m, 3H), 7,25 (d, 2H), 5.25 in (d, 1H), 4,98-4,78 (m, 1H), 4,27-to 4.14 (m, 4H), 3,18-is 3.08 (m, 1H), 3,05-2,97 (m, 1H), of 1.88 (m, 1H), 1,61 (m, 10H), of 1.23 (t, 6H).

Example 119:tert-butyl ester (S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1128)

Followed General procedure I-3 using hydrochloride tert-butyl ether complex of L-serine.13C NMR (151 MHz, DMSO) δ 169,55, 166,25, 150,81, 133,45, 131,32, 130,78, 128,61, 127,22, 126,55, 126,42, 125,68, 125,54, 125,20, 123,15, 122,92, 80,43, 61,20, 56,10, 51,06, 50,28, 38,33, 36,86, 32,88, 28,80, 27,61, 24,40, 20,17.

Example 120:5-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}nicotinic acid (compound 1129)

Followed General procedure I-1, using ethyl ester 5-aminonicotinic acid.1H NMR (600 MHz, DMSO) δ 9,12 (d, 1H), 8,79 (d, 1H), total of 8.74-to 8.70 (m, 1H), at 8.36 (d, 1H), 7,94 (d, 1H), a 7.85 (d, 2H), 7,80 (DD, 2H), EUR 7.57-of 7.48 (m, 3H), 7,22 (d, 2H), 4,86 was 4.76 (m, 1H), 3,12 totaling 3.04 (m, 1H), 2,97-2,90 (m, 1H), 1,95-of 1.30 (m, 11H).

Example 121:4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid (compound 1130)

Followed General procedure I-1, using ethyl complex is ether 4-aminobenzoic acid. The intermediate ethyl ester hydrolyzed following General procedure J, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ 10,41 (s, 1H), 8,35 (d, 1H), 7,97-7,88 (m, 5H), 7,86-to 7.77 (m, 4H), to 7.59-to 7.50 (m, 3H), 7,22 (d, 2H), 4,84 (sh, 1H), 3,11 totaling 3.04 (m, 1H), 3,02 of 2.92 (m, 1H), 1,92-1,32 (m, 11H).

Example 122:hydrochloride of ester methyl 4-methoxy-3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid (compound 1131)

Followed General procedure I-1, using methyl 3-amino-4-methoxybenzoate. The product was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (600 MHz, DMSO) δ 9,48 (s, 1H), cent to 8.85 (m, 2H), 8,42 (d, 1H), 8,35 (d, 1H), 8,03 (t, 2H), 7,89 (d, 3H), 7,83 (DD, 1H), 7,69-to 7.59 (m, 3H), 7,31 (d, 2H), 7.23 percent (d, 1H), of 5.55 (s, 1H), 3,93 (s, 3H), of 3.84 (s, 3H), 3,30-up 3.22 (m, 1H), 3,16-of 3.07 (m, 1H), 2,04-to 1.77 (m, 5H), 1,72 (d, 3H), 1.70 to to 1.60 (m, 2H), 1.56 to 1,49 (m, 1H).

Example 123:hydrochloride of 2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid (compound 1132)

Followed General procedure I-1, using methyl 2-aminobenzoate. The intermediate methyl ester hydrolyzed following General procedure J, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ 8,69 (d, 1H), 8,35 (d, 1H), of 8.06 (DD, 1H), 8,00 (DD, 2H), of 7.90 (d, 3H), to 7.67 to 7.62 (m, 2H), to 7.59(t, 1H), 7,56-7,49 (m, 1H), 7,34 (d, 2H), 7,12 (t, 1H), of 5.53-of 5.34 (m, 1H), 3,24-3,18 (m, 1H), 3,18-3,11 (m, 1H), from 2.00 to 1.76 (m, 5H), 1,73 is 1.48 (m, 6H).

Example 124:hydrochloride (carboxymethyl-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1133)

Followed General procedure I-1, using diethylaminoacetate. Intermediate diethyl ester hydrolyzed following General procedure J,getting listed at the beginning of the connection.1H NMR (600 MHz, DMSO) δ a 8.34 (d, 1H), 8,00 (d, 1H), of 7.96 (d, 1H), to 7.84 (d, 1H), 7.62mm (t, 2H), 7,58 (t, 1H), 7,24 (d, 2H), 7,17 (d, 2H), are 5.36 (s, 1H), 4.00 points (s, 2H), 3,79 (s, 2H), 3,18-3,13 (m, 1H), 3,06-2,99 (m, 1H), 1,92-of 1.74 (m, 5H), of 1.65 (d, 3H), 1.60-to of 1.46 (m, 3H).

Example 125:1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}methyl)cyclopentanecarbonyl acid (compound 1134)

Followed General procedure I-1 using ethyl 1-(aminomethyl)cyclopentanecarboxylate. The intermediate ethyl ester hydrolyzed following General procedure J, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ a 8.34 (d, 1H), 8,15 (d, 1H), to 7.93 (d, 1H), to 7.77 (DD, 2H), to 7.64 (d, 2H), 7,55-of 7.48 (m, 3H), 7,10 (d, 2H), 4,70 (K, 1H), 3,48 (d, 2H), 3,06 are 2.98 (m, 1H), 2,89-to 2.85 (m, 1H), 1,95-to 1.82 (m, 3H), 1,81 is 1.70 (m, 2H), 1,68 of 1.46 (m, 10H), 1,46-of 1.36 (m, 1H), of 1.44 (d, 3H), 1,35-of 1.26 (m, 1H).

Example 126:hydrochloride of 1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopentanecarboxylic acid (with the Association 1135)

Followed General procedure I-1, using the hydrochloride of methyl 1-amino-1-cyclopentane-carboxylate. The intermediate methyl ester hydrolyzed following General procedure J, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ 11,93 (sh, 1H), 8,88 (s, 2H), 8,42 (s, 1H), 8.34 per (d, 1H), 8,01 (DD, 2H), 7,89 (d, 1H), to 7.77 (d, 2H), 7,69-7,63 (m, 2H), to 7.61 (t, 1H), 7.23 percent (d, 2H), 5,54 (sh, 1H), 3.27 to 3,20 (m, 1H), 3,12-3,05 (m, 1H), 2,18-of 2.09 (m, 2H), 2.06 to of 1.57 (m, 16H), 1,54 of 1.46 (m, 1H).

Example 127:hydrochloride 3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1136)

Followed General procedure J, using methyl ester 3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1088).1H NMR (600 MHz, DMSO) δ for 9.47 (sh, 1H), 8,46 (t, 1H), 8,35 (d, 1H), of 7.97 (d, 1H), 7,89 (d, 1H), 7,72 (d, 2H), 7,60-7,52 (m, 3H), 7,18 (d, 2H), 5,15 (sh, 1H), of 3.45 (DD, 2H), 3,20-3,11 (m, 1H), 3,06 are 2.98 (m, 1H), 2,54-2,48 (m, 2H)(blocked DMSO signal), 2,00-of 1.81 (m, 3H), 1,79 is 1.58 (m, 5H), 1,57-of 1.36 (m, 3H).

Example 128:hydrochloride (1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclohexyl)acetic acid (compound 1137)

Followed General procedure I-1, using methyl ester (1-amino-cyclohexyl)acetic acid. The intermediate methyl ester hydrolyzed following General procedure is J, to get listed at the beginning of the connection.1H NMR (600 MHz, DMSO) δ 12,94-10,67 (sh, 1H), 8,83 (s, 2H), 8.34 per (d, 1H), 8,02 (DD, 2H), 7,89 (d, 1H), of 7.70 (d, 2H), 7.68 per-to 7.64 (m, 2H), to 7.61 (t, 1H), 7,47 (s, 1H), 7,20 (m, 2H), 5,59-of 5.50 (m, 1H), 3,30-3,20 (m, 1H), 3,11-3,03 (m, 1H), 2,75 (s, 2H), 2,32 (m, 2H), 2,02 is 1.86 (m, 3H), 1.85 to around 1.74 (m, 2H), 1,72 (d, 3H), 1,68-of 1.57 (m, 2H), 1,57-of 1.41 (m, 8H), 1.30 and of 1.20 (m, 1H).

Example 129:ethyl ester 1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine]cyclopropanecarboxylic acid (compound 1138)

Followed General procedure I using the hydrochloride of ethyl ether complex 1-aminocyclopropane-1-carboxylic acid.13C NMR (151 MHz, DMSO) δ 172,07, 167,00, 151,01, 142,43, 133,45, 131,26, 130,81, 128,59, 127,16, 126,40, 125,60, 125,54, 125,15, 123,08, 122,95, 60,43, 60,13, 51,10, 50,17, 38,57, 36,92, 33,25, 33,00, 28,96, 24,62, 20,22, 17,49, 16,62, 13,98.

Example 130:1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopropanecarbonyl acid (compound 1139)

Followed General procedure J, using ethyl ester 1-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopropanecarboxylic acid (compound 1138).13C NMR (151 MHz, DMSO) δ 174,06, 167,01, 150,30, 133,58, 131,68, 130,79, 128,88, 127,45, 127,41, 126,59, 126,53, 126,24, 125,71, 125,63, 123,77, 122,91, 51,00, 50,89, 36,68, 33,34, 33,15, 32,56, 28,15, 23,60, 20,10, 17,01, 16,57.

Example 131:1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}methyl)cyclopropanecarbonyl sour is a (connection 1140)

Followed General procedure I-1, using ethyl ester 1-(aminomethyl)cyclopropanecarboxylic acid. The intermediate ethyl ester hydrolyzed following General procedureJ, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ 8,35 (d, 1H), 8,21 (t, 1H), to 7.93 (d, 1H), 7,80 (d, 1H), to 7.77 (d, 1H), to 7.67 (d, 2H), 7,52 (DK, 3H), 7,10 (d, 2H), 4,76 (sh, 1H), 3,52 (d, 2H), 3,06-of 2.97 (m, 1H), 2,93-2,87 (m, 1H), 1.91 a-1,81 (m, 1H), 1,80 is 1.70 (m, 2H), 1,69-of 1.62 (m, 1H), 1,58-to 1.38 (m, 6H), 1,37 of 1.28 (m, 1H), 1,02 (K, 2H), 0,89 (DD, 2H).

Example 132:2-methyl-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1141)

Followed General procedure I-1, using the hydrochloride of ester methyl 2-methylalanine. The intermediate methyl ester hydrolyzed following General procedure J, receiving specified in the header of the connection.1H NMR (300 MHz, DMSO) δ 8,35 (d, 1H), 8,31 (s, 1H), 7,98-7,89 (m, 1H), 7,82 (DD, 2H), 7,69 (d, 2H), to 7.59-7,46 (m, 3H), 7,11 (d, 2H), a 4.83 (K, 1H), 3,13-2,99 (m, 1H), 2,97-is 2.88 (m, 1H), 1,97-to 1.21 (m, 8H), 1.50 in (d, 3H), the 1.44 (s, 6H).

Example 133:1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}azetidin-3-carboxylic acid (compound 1142)

Followed General procedure I-1, using the hydrochloride of the methyl ether complex 3-azetidinone acid. The intermediate methyl ester Hydra who was litovali, following the General procedureJ, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ a 8.34 (d, 1H), 7,97-to $ 7.91 (m, 1H), 7,81 (d, 1H), to 7.77 (d, 1H), 7,53 (m, 3H), of 7.48 (d, 2H), 7,13 (d, 2H), 4,82 (sh, 1H), 4,43 (m, 1H), or 4.31 (m, 1H), 4,19 (m, 1H), Android 4.04 (m, 1H), 3.43 points (m, 1H), to 3.02 (m, 1H), 2,90 (m, 1H), 1,90-of 1.65 (m, 4H), 1,61-of 1.30 (m, 7H).

Example 134:(methyl-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1143)

Followed General procedure I-1, using the hydrochloride of ethyl ether complex n-methylglycine. The intermediate ethyl ester hydrolyzed following General procedureJ, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ a 8.34 (d, 1H), 7,94 (d, 1H), 7,82 (d, 1H), 7,79-7,74 (m, 1H), EUR 7.57-of 7.48 (m, 3H), 7,27 (d, 1H), 7,12 (dt, 3H), 4,91 was 4.76 (sh, 1H), 4,11 (s, 1H), 3,89 (s, 1H), 3,06 are 2.98 (m, 1H), 2,97-2,90 (m, 4H), 1.91 a-to 1.67 (m, 4H), 1,63-of 1.53 (m, 1H), 1,53-of 1.40 (m, 5H), 1,40-of 1.30 (m, 1H).

Example 135:4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}butyric acid (compound 1144)

Followed General procedure I-1, using the hydrochloride of ethyl 4-aminobutyrate. The intermediate ethyl ester hydrolyzed following General procedureJ, receiving specified in the header of the connection.1H NMR (600 MHz, DMSO) δ 8,35 (t, 2H), 7,97-to $ 7.91 (m, 1H), 7,81 (d, 1H), to 7.77 (d, 1H), 7,68 (d, 2H), 7,53 (m, 3H), 7,10 (d, 2H), 4,79 (s, 1H), 3,24 (DD, 2H), to 3.02 (t, 1H), 2,92 (s, 1H, in), 2.25 (t, 2H), 1,73 (t, 2H,), 1,92-to 1.63 (m, 4H), 1.60-to of 1.29(m, 7H).

Example 136:ethyl ester 1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid (compound 1145)

Followed General procedure I-1, using ethyl ester 4-piperidinecarboxylic acid.13C NMR (126 MHz, DMSO) δ 173,69, 169,04, 148,70, 142,38, 133,45, 133,30, 130,83, 128,57, 126,60, 126,51, 126,40, 125,60, 125,52, 125,13, 123,04, 122,93, 59,87, 50,93, 50,00, 46,26, 39,92, 38,67, 36,85, 32,98, 28,93, 27,84, 24,50, 20,24, 13,96.

Example 137:1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid (compound 1146)

Followed General procedure J, using ethyl ester 1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid (compound 1145).1H NMR (600 MHz, DMSO) δ 12,21 (sh, 1H), 9,37 (d, 2H), 8,35 (d, 1H), 8,13 (d, 1H), to 7.99 (DD, 2H), 7,69-rate of 7.54 (m, 3H), 7,25 (DD, 4H), of 5.50 (s, 1H), 4,43-4,18 (m, 1H), 3,60-to 3.41 (m, 1H), 3,24-of 3.12 (m, 2H), 3,11-and 2.79 (m, 2H), 2.57 m-2,47 (m, 1H), 2,11 was 1.69 (m, 10H), 1,68-to 1.38 (m, 5H).

Example 138:ethyl ester (cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1147)

To a solution of 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (Sp. 54, 20 mg) in 400 μl of DMF was added diisopropylethylamine (3 EQ.) and hexaphosphate bromo-Tris-pyrrolidino-phosphonium (PyBroP, 1 EQ.). The solution of ohlord is whether in a bath with ice and add ethyl ester of N-cyclohexylglycine (3 equiv.) and then 1-hydroxy-7-asobancaria (HOAt, 3 EQ.). After stirring over night at K.T. the reaction mixture was diluted with aqueous NaHCO3and was extracted with dichloromethane. The organic extracts were concentrated in vacuum and purified by HPLC-MS.1H NMR (500 MHz, DMSO) δ of 8.25 (d, 1H), 7,98 (s, 2H), 7,82 (s, 1H), to 7.59 (s, 3H), 7,12 (t, 4H), 5,51-5,31 (m, 1H), 4,10 (K, 2H), 3,99 (s, 2H), 3,69 is 3.57 (m, 1H), 3,36-up 3.22 (m, 1H), 3,20-3,10 (m, 1H), 2,10-of 1.95 (m, 2H), 1,86-of 1.64 (m, 12H), 1.56 to to 1.38 (m, 4H), to 1.19 (t, 3H), 1,13-and 0.98 (m, 3H).

Example 139:(cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1148)

Followed General procedure J, using ethyl ester (cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1147). LC-MS (method B): RT = 3,23, [M+H]+= 513,5.

Example 140:4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-((R)-2-oxitetraciclina-3-yl)benzamide (connection 1149)

Followed General procedure I using the hydrochloride of (R)-(+)-2-amino-4-butyrolactone.13C NMR (75 MHz, DMSO) δ 175,25, 165,82, 151,24, 142,45, 133,46, 130,82, 130,77, 128,58, 127,08, 126,54, 126,41, 125,59, 125,53, 125,14, 123,10, 122,97, 65,21, 51,16, 50,20, 48,23, 38,56, 36,92, 32,93, 29,01, 27,90, 24,60, 20,23.

Example 141:N-cyanomethyl-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1150)

Followed about what her procedure I, using hydrochloride aminoacetonitrile.1H NMR (300 MHz, DMSO) δ remaining 9.08 (t, 1H), 8,35 (d, 1H), 7,97-7,87 (m, 1H), 7,84-7,66 (m, 4H), 7,58-the 7.43 (m, 3H), 7,13 (d, 2H), 4,66 (s, 1H), 4,29 (d, 2H), 3,12-2,96 (m, 1H), 2,94-2,82 (m, 1H), 1,95-to 1.21 (m, 12H).

Example 142:N-(4-cyano-1H-pyrazole-3-yl)-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1151)

Followed General procedure I, using 4-cyano-5-aminopyrazole.1H NMR (300 MHz, DMSO) δ 8,35 (d, 1H), 8,02 (s, 1H), of 7.96-of 7.70 (m, 6H), 7,56-the 7.43 (m, 3H), 7,22-7,10 (m, 2H)and 4.65 (K, 1H), 3,14 are 2.98 (m, 1H), 2,90-of 2.81 (m, 1H), 2,23 (sh, 1H), 1,97-of 1.20 (m, 11H).

Example 143:benzyl ester of (R)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1152)

Followed General procedure I-3 using hydrochloride benzyl complex ester of D-serine.1H NMR (600 MHz, DMSO) δ of 8.47 (d, 1H), 8,35 (d, 1H), 7,92 (d, 1H), 7,76 (DD, 2H), 7,73 (d, 2H), 7,55-7,46 (m, 3H), 7,40-7,29 (m, 5H), 7,11 (d, 2H), further 5.15 (DD, 2H), 5,07 (t, 1H), 4,70-to 4.62 (m, 1H), 4,57 (DD, 1H), 3,86-of 3.78 (m, 2H), 3,03 (t, 1H), 2,87 (s, 1H), 2,22 (sh, 1H), 1.93 and-1,82 (m, 1H), 1,82 is 1.70 (m, 2H), and 1.63 (d, 1H), 1,54-of 1.35 (m, 6H), of 1.29 (t, 1H).

Example 144:benzyl ester (S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1153)

Followed General procedure I-3 using hydrochloride benzyl ether complex of L-serine.1NMR (600 MHz, DMSO) δ of 8.47 (d, 1H), 8,35 (d, 1H), 7,92 (d, 1H), to 7.77 (DD, 2H), 7,73 (d, 2H), 7,55-7,46 (m, 3H), 7,39-7,29 (m, 5H), 7,12 (d, 2H), further 5.15 (DD, 2H), 5,07 (t, 1H), 4,66 (sh, 1H), 4,57 (dt, 1H), 3,86-of 3.78 (m, 2H), 3,03 (t, 1H), 2.91 in-and 2.83 (m, 1H), 2,22 (sh, 1H), 1,94 of-1.83 (m, 1H), 1,81 is 1.70 (m, 2H), 1,67-to 1.59 (m, 1H), 1,53-of 1.24 (m, 7H).

Example 145:methyl ester (S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1154)

Followed General procedure I-3 using the hydrochloride of the methyl complex ester of L-serine.13C NMR (126 MHz, DMSO) δ 171,12, 166,38, 151,16, 142,39, 133,58, 131,16, 130,92, 128,71, 127,39, 126,58, 126,55, 125,75, 125,65, 125,29, 123,24, 123,06, 61,09, 55,58, 51,84, 51,24, 50,36, 38,55, 37,03, 33,07, 29,06, 24,62, 20,32.

Example 146:methyl ester of (R)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1155)

Followed General procedure I-3 using the hydrochloride of the methyl complex ester of D-serine.1H NMR (600 MHz, DMSO) δ 8,43 (d, 1H), 8,35 (d, 1H), to 7.93 (d, 1H), to 7.77 (DD, 2H), 7,74 (d, 2H), 7,56-7,46 (m, 3H), 7,12 (d, 2H), of 5.05 (t, 1H), 4,69 (s, 1H), 4,51 (DD, 1H), 3,78 (t, 2H), to 3.64 (s, 3H), 3,03 (m, 1H), is 2.88 (s, 1H), 1.93 and of-1.83 (m, 1H), 1,82 is 1.70 (m, 2H), 1,68 is 1.60 (m, 1H), 1,54 of 1.46 (m, 2H), 1,46 is 1.35 (m, 1H), of 1.44 (d, 3H), 1,35-1,25 (m, 1H).

Example 147:the hydrochloride of ethyl ether complex (S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1156)

Followed General procedure I-3 using the hydrochloride of ethyl ether complex of L-serine. The product was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ 9,42 (s, 2H), 8,51 (d, 1H), 8,35 (d, 1H), 8,15 (d, 1H), 7,99 (t, 2H), to 7.84 (d, 2H), to 7.61 (dt, 13,5, 3H), 7,28 (d, 2H), 5,57-5,43 (m, 1H), 5,24-4,99 (sh, 1H), 4,48 (DD, 1H), 4,11 (K, 2H), 3,80 (d, 2H), 3,31-is 3.08 (m, 2H), 2,10-of 1.36 (m, 12H), to 1.19 (t, 3H).

Example 148:hydrochloride 3-hydroxy-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1157)

tert-Butyl ester (S)-3-hydroxy-2-{4-[(1S,3S)-3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1128, 150 mg) suspended in 5 ml of HCl (4 M in dioxane) and stirred over night at room temperature. Diethyl simple ether was added to the reaction mixture and the thus obtained precipitate was filtered, washed with additional number of ordinary ether and dried.13C NMR (151 MHz, DMSO) δ 171,84, 166,00, 148,26, 133,82, 133,34, 131,63, 130,23, 129,77, 128,94, 127,50, 127,02, 126,43, 126,14, 125,52, 124,61, 122,30, 61,04, 55,58, 51,97, 48,48, 35,74, 33,44, 30,97, 25,84, 20,79, 19,32.

Example 149:(R)-4-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}butyric acid (compound 1158)

13C NMR (75 MHz, DMSO) δ 173,97, 166,15, 150,61, 141,77, 133,45, 131,49, 130,77, 128,61, 127,16, 126,60, 126,39, 125,70, 125,53, 125,21, 123,18, 122,90, 57,67, 51,01, 50,27, 50,12, 38,18, 36,83, 33,79, 32,87, 28,76, 24,28, 20,16.

Example 150:formate N-tert-butoxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1159)

Followed General procedure I using the hydrochloride of O-(tert-butyl)hydroxylamine.13C NMR (151 MHz, DMSO) δ 165,88, 163,70, 150,90, 142,24, 133,44, 130,78, 130,22, 128,59, 127,10, 126,50, 126,45, 125,63, 125,53, 125,16, 123,09, 122,92, 80,68, 51,00, 50,13, 38,43, 36,93, 32,99, 28,86, 26,39, 24,52, 20,18.

Example 151:formate N-tert-butoxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1160)

Followed General procedure I-2, using the hydrochloride of O-(tert-butyl)hydroxylamine.13C NMR (151 MHz, DMSO) δ 165,89, 163,24, 150,59, 141,24, 133,38, 130,75, 130,31, 128,62, 127,20, 126,66, 125,80, 125,52, 125,24, 123,09, 122,71, 80,70, 50,03, 49,49, 36,60, 35,95, 32,93, 30,31, 26,40, 24,01, 20,33.

Example 152:formate N-methoxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1161)

Followed General procedure I using the hydrochloride of O-methylhydroxylamine.13C NMR (75 MHz, DMSO) δ 163,56, 150,81, 141,06, 133,57, 130,84, 129,75, 128,77, 126,99, 126,72, 125,97, 125,65, 125,44, 123,44, 122,96, 63,18, 51,10, 50,60, 37,77, 36,87, 32,69, 28,59, 24,02, 20,8.

Example 153:formate N-methoxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1162)

Followed General procedure I-2, using the hydrochloride of O-methylhydroxylamine.13C NMR (151 MHz, DMSO) δ 163,43, 150,64, 140,70, 133,38, 130,71, 129,65, 128,65, 126,94, 126,83, 126,76, 125,89, 125,52, 125,31, 123,21, 122,69, 63,08, 50,05, 49,62, 36,52, 35,63, 32,71, 30,11, 23,77, 20,27.

Example 154:4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-(tetrahydrofuran-3-ylethoxy)benzamide (connection 1163)

Followed General procedure I, using O-(tetrahydrofuran-3-ylmethyl)hydroxylamine (WO 2005054179).13C NMR (75 MHz, DMSO) δ 163,30, 150,95, 141,75, 133,47, 130,78, 129,63, 128,63, 126,89, 126,61, 125,73, 125,54, 125,24, 123,19, 122,91, 77,10, 69,88, 66,72, 51,05, 50,33, 38,13, 37,28, 36,88, 32,78, 28,78, 28,37, 24,27, 20,15.

Example 155:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-(tetrahydrofuran-3-ylethoxy)benzamide (connection 1164)

Followed General procedure I-2, using O-(tetrahydrofuran-3-ylmethyl)hydroxylamine (WO 2005054179). LC-MS (method B): RT = 2,49, [M+H]+= 473,3.

Example 156:bis-formate N-methoxy-N-methyl-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1165)

Followed General procedure I using the hydrochloride of N,O-dimethylhydroxylamine.1H NMR (300 MHz, DMSO) δ a 8.34 (d, 1H), to 8.20 (s, 2H), 7,97-7,88 (m, 1H), 7,76 (t, 2H), EUR 7.57-7,39(m, 5H), to 7.09 (d, 8,2, 2H), 4,69 (K, 1H), 3,53 (s, 3H), up 3.22 (s, 3H), 3,09-2,95 (m, 1H), 2.91 in-2,82 (m, 1H), 1,95-to 1.60 (m, 4H), 1,57-to 1.21 (m, 7H).

Example 157:N-methoxy-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1166)

Followed General procedure I-2, using the hydrochloride of N,O-dimethylhydroxylamine.1H NMR (300 MHz, DMSO) δ 8.34 per-of 8.27 (m, 1H), of 7.96-7,88 (m, 1H), 7,76 (DD, 2H), 7,56-the 7.43 (m, 5H), from 7.24 (d, 2H), 4,77 (K, 1H), 3,54 (s, 3H), 3,23 (s, 3H), 3,17-of 3.06 (m, 1H), 2,87 is 2.80 (m, 1H), 1,90 is 1.34 (m, 11H).

Example 158:N-benzyloxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1167)

Followed General procedure I using the hydrochloride of O-benzyl-hydroxylamine.13C NMR (75 MHz, DMSO) δ 163,90, 151,07, 141,88, 136,04, 133,57, 130,89, 129,74, 128,86, 128,73, 128,30, 128,25, 127,03, 126,71, 125,82, 125,65, 125,33, 123,31, 123,01, 76,92, 51,15, 50,40, 38,26, 36,98, 32,89, 28,87, 24,39, 20,26.

Example 159:N-benzyloxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1168)

Followed General procedure I-2, using the hydrochloride of O-benzylhydroxylamine.13C NMR (75 MHz, DMSO) δ 163,71, 150,20, 139,74, 135,94, 133,41, 130,66, 129,73, 128,78, 128,71, 128,21, 128,17, 127,14, 127,01, 126,72, 126,07, 125,53, 125,43, 123,46, 122,63, 76,83, 50,05, 49,89, 36,39, 35,08, 32,39, 29,79, 23,35, 20,18.

Example 160:N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1169)

To a solution of N-benzyloxy-4-[3-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1168, 17 mg) in 700 μl) was added 2 mg of palladium on carbon (10%) and the mixture was hydrogenosomal with vigorous stirring over night at K.T. Catalyst was filtered through celite and the filtrate was concentrated in vacuum. The product was purified by HPLC.1H NMR (600 MHz, DMSO) δ 8,32 (d, 1H), 8,19 (s, 1H), 7,92 (DD, 1H), 7,78 (d, 1H), 7,74 (d, 1H), 7,56 (d, 2H), 7,53-7,46 (m, 3H), 7,20 (m, 2H), 4.75 in (K, 1H), 3,11 was 3.05 (m, 1H), 2,83 (sh, 1H), 1,86-of 1.73 (m, 3H), 1,62-of 1.55 (m, 1H), 1,51-of 1.35 (m, 7H).

Example 161:N-hydroxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1170)

4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056, 50 mg) suspended in a mixture of 1:1 DMF and THF (each 150 ml) and cooled to -20°C. was Added N-methylmorpholine (16 μl) and isobutylparaben (18 μl). The reaction mixture is kept at -20°C for two days, after which was added O-(trimethylsilyl)hydroxylamine (26 μl). The mixture was slowly heated to K.T. under stirring for 3 hours and then extinguished with ethyl acetate and KH2PO4. The aqueous phase was extracted 6 times with ethyl acetate. The combined organic extracts were concentrated in vacuum and purified by chromatography.13C NMR (75 MHz, DMSO) δ 164,14, 150,60, 142,39, 133,46, 130,81, 130,09, 128,58, 126,67, 126,50, 126,42, 125,60, 125,53, 125,14, 123,08, 122,94, 51,06, 50,13, 38,58, 36,90, 32,94, 28,97, 24,55, 20,22.

Example 162:N-(2-morpholine-4-yl-2-oksidoksi)-4-[(1S,3S)-3-((R)-1-naphthalin-ylethylamine)cyclohexyl]benzamide (connection 1171)

Followed General procedure I, using chloride 4-[2-(ammoniac)acetyl]the research.13C NMR (151 MHz, DMSO) δ 165,43, 163,31, 151,10, 141,54, 133,44, 130,74, 129,15, 128,63, 126,99, 126,67, 126,61, 125,75, 125,53, 125,26, 123,19, 122,88, 73,30, 66,00, 65,86, 50,98, 50,32, 45,03, 41,42, 37,99, 36,84, 32,71, 28,64, 24,19, 20,10.

Example 163:N-(2-morpholine-4-yl-2-oksidoksi)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1172)

Followed General procedure I-2, using chloride 4-[2-(ammoniac)acetyl]the research.13C NMR (75 MHz, DMSO) δ 165,46, 163,35, 150,94, 141,00, 133,40, 130,74, 129,24, 128,64, 127,08, 126,77, 125,84, 125,52, 125,28, 123,14, 122,72, 73,32, 66,02, 65,89, 50,09, 49,57, 45,07, 41,45, 36,60, 35,85, 32,79, 30,23, 23,87, 20,30.

Example 164:N-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}methanesulfonamide (connection 1173)

Followed General procedure I, using methanesulfonamide.1H NMR (300 MHz, DMSO) δ a 8.34 (d, 1H), 8,03-7,76 (m, 5H), 7,65 is 7.50 (m, 3H), was 7.08 (d, 2H), and 5.30-5,17 (m, 1H), 3,16-2,96 (m, 2H), 2,90 (s, 3H), 1,92 by 1.68 (m, 5H), 1,67-of 1.40 (m, 6H).

Example 165:methyl ester 4R-hydroxy-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2S-carboxylic acid (compound 1174)

Followed General procedure I using the hydrochloride of the methyl ether complex L-hydroxyproline.1H NMR (600 MHz, DMSO) δ 8,35 (d, 1H), to 7.93 (d, 1H), 7,78 (DD, 2H), 7,56-7,47 (m, H), 7,39 (d, 2H), 7,11 (d, 2H), 5,07 (s, 1H), 4,74 (s, 1H), 4,58-to 4.52 (m, 1H), of 3.73 (DD, 1H), 3,66 (s, 3H), 3,29 (s, 1H), to 3.02 (t, 1H), 2,89 (s, 1H), 2,18 (DD, 1H), 1,98 is 1.91 (m, 1H), 1,90-to 1.82 (m, 1H), 1,80-1,71 (m, 2H), 1,69-to 1.63 (m, 1H), 1,58-to 1.38 (m, 6H), 1,37-of 1.27 (m, 1H), LC/MS (method B): RT = 2,42, [M+H]+= 501,5.

Example 166:4R-hydroxy-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2S-carboxylic acid (compound 1175)

Followed General procedure J, using methyl ester of 4-hydroxy-1-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2-carboxylic acid (compound 1174).1H NMR (600 MHz, DMSO) δ 8,35 (d, 1H), 7,92 (d, 1H), to 7.77 (DD, 2H), 7,55-7,46 (m, 3H), 7,38 (d, 2H), 7,10 (d, 2H), 5,02 (sh, 1H), 4,70 (K, 1H), 4,50-4,43 (m, 1H), 4,27-to 4.23 (m, 1H), 3,70 (DD, 1H), 3,28 (d, 1H), 3,06-of 2.97 (m, 1H), 2,89-and 2.83 (m, 1H), 2.21 are of 2.15 (m, 1H), 1,97-to 1.82 (m, 2H), 1,80-1,71 (m, 2H), 1,68-of 1.62 (m, 1H), 1,54-of 1.35 (m, 6H), 1,34-1,25 (m, 1H).

Example 167:the hydrochloride of N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}methanesulfonamide (connection 1176)

Followed General procedure I-2 using methanesulfonamide. The product was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (600 MHz, DMSO) δ 9,70-to 8.62 (m, 1H), with 8.33 (d, 1H), 8,04-of 7.70 (m, 5H), to 7.64-to 7.50 (m, 3H),? 7.04 baby mortality (s, 2H), 5,49-to 4.87 (m, 1H), 3,14 are 2.98 (m, 2H), 2,86 (s, 3H), 1,94-of 1.85 (m, 1H), 1,82 to 1.47 (m, 9H), 1,46 is 1.34 (m, 1H).

General procedure K

To Rast is the oru arylboronic acid (4.6 mmol) and [(1,4-hydroquinone)rhodium(COD)]BF 4(Son et al.,J. Am. Chem. Soc.2005, 127, 12238) (2 mol.%) in a mixture of water/dimethoxyethane (1:1, 20 ml, degassed) was added Cyclopentanone (4.6 mmol) and LiOH (8 mol.%). The mixture was heated to 50°C and was stirred overnight. Added more water and the mixture was extracted with dichloromethane. The organic phase was separated, dried and concentrated in vacuo to a brown oil. This crude intermediate compound was re-dissolved in 40 ml of dichloroethane. After adding (+)-(R)-1-naphthalene-1-ylethylamine (4.6 mmol) and NaBH(OAc)3(1.7 EQ.) the reaction mixture was stirred over night at K.T. Mixture was diluted with dichloromethane, washed with aqueous NaHCO3, water and saturated salt solution. The organic phase was dried, concentrated in vacuo and purified on silica gel to colorless oil. Diastereoisomer was shared by chiral HPLC.

Example 168:ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1177/1178/1179/1180)

Followed General procedure K using 4-(2-ethoxy-2-oksidoksi)phenylboronic acid. Four received diastereoisomers were separated using chiral HPLC on a column Chiralpak AD-H 250×20 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with mixture of N-heptane:ethanol:NEt3:CH3COOH(75:25:0,1:0,1); consumption = 7,0 ml/min 1177 Connection: RT = 11,05.1 C NMR (151 MHz, DMSO) δ 168,78, 155,62, 141,94, 138,53, 133,42, 130,87, 128,59, 127,74, 126,50, 125,67, 125,56, 125,18, 123,01, 122,91, 114,14, 64,60, 60,47, 56,58, 51,18, 42,82, 42,06, 32,52, 32,14, 24,24, 13,96. Connection 1178: RT = 12,77.13C NMR (151 MHz, DMSO) δ 168,77, 155,55, 142,09, 138,62, 133,39, 130,95, 128,58, 127,70, 126,49, 125,65, 125,57, 125,17, 122,95, 122,93, 114,14, 64,59, 60,46, 55,97, 51,02, 42,08, 40,44, 33,65, 33,23, 24,15, 13,95. Connection 1179: RT = 18,35.13C NMR (151 MHz, DMSO) δ 168,75, 155,54, 142,03, 138,60, 133,39, 130,83, 128,59, 127,63, 126,54, 125,67, 125,54, 125,19, 123,01, 122,89, 114,14, 64,57, 60,45, 56,16, 50,81, 42,00, 41,33, 33,30, 32,93, 24,05, 13,93. Connection 1180: RT = 23,96.13C NMR (151 MHz, DMSO) δ 168,91, 155,77, 141,97, 138,42, 133,53, 130,96, 128,75, 127,82, 126,80, 125,87, 125,69, 125,37, 123,20, 123,01, 114,28, 64,72, 60,60, 56,62, 51,37, 42,66, 42,05, 32,30, 31,84, 24,09, 14,09.

Example 169:methyl ester 3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1181/1182/1183/1184)

Followed General procedure K using 4-(2-methoxycarbonylethyl)phenylboronic acid. Four of the resulting diastereoisomer was shared by preparative chiral HPLC on a column Chiralpak AD-H 250×20 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with mixture of N-heptane:2-propanol:NEt3:CH3COOH(75:25:0,1:0,1); consumption = 7,0 ml/min 1181 Connection: RT = 7,74.13C NMR (126 MHz, DMSO) δ 172,59, 143,57, 142,01, 137,65, 133,41, 130,87, 128,57, 127,92, 126,80, 126,47, 125,63, 125,54, 125,15, 122,99, 122,90, 56,66, 51,21, 51,15, 43,23, 41,97, 34,84, 32,59, 31,99, 29,73, 24,23. Connection 1182: RT = 8,75.13C NMR (126 MHz, DMSO) δ 172,59, 143,70, 142,08, 137,57, 133,40, 130,95, 128,56, 127,92, 126,77, 126,47,125,62, 125,55, 125,15, 122,95, 122,93, 56,07, 51,14, 51,07, 42,50, 40,37, 34,82, 33,68, 33,06, 29,71, 24,13. Connection 1183: RT = 11,47.13C NMR (126 MHz, DMSO) δ 172,58, 143,74, 142,15, 137,56, 133,40, 130,86, 128,58, 127,92, 126,71, 126,47, 125,62, 125,53, 125,15, 122,99, 122,92, 56,30, 51,14, 50,92, 42,42, 41,31, 34,79, 33,14, 33,06, 29,69, 24,14. Connection 1184: RT = 15,95.13C NMR (126 MHz, DMSO) δ 172,60, 143,44, 141,96, 137,66, 133,40, 130,88, 128,58, 127,92, 126,76, 126,50, 125,63, 125,54, 125,15, 122,99, 122,91, 56,63, 51,34, 51,15, 42,96, 42,24, 34,81, 32,06, 31,86, 29,72, 24,12.

Example 170:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1185)

Followed General procedure J, using ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1178).13C NMR (75 MHz, DMSO) δ 171,24, 156,64, 137,18, 136,14, 133,30, 130,49, 128,74, 127,83, 127,45, 126,43, 125,68, 125,53, 123,96, 122,44, 113,96, 66,07, 55,36, 50,31, 42,31, 37,78, 33,41, 31,62, 21,55.

Example 171:{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1186)

Followed General procedure J, using ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1180).13C NMR (151 MHz, DMSO) δ 170,60, 156,80, 141,57, 136,68, 133,37, 130,84, 128,59, 127,26, 126,57, 125,70, 125,55, 125,19, 123,06, 122,85, 114,01, 67,44, 56,46, 51,22, 42,56, 42,24, 32,23, 31,56, 23,97.

Example 172:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1187)

Followed General procedure J, using ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1177).13C NMR (75 MHz, DMSO) δ 171,08, 156,66, 136,78, 136,00, 133,35, 130,36, 128,78, 127,89, 127,48, 126,50, 125,73, 125,53, 123,89, 122,37, 114,06, 65,94, 55,64, 50,45, 42,84, 32,02, 29,87, 21,92 (one aliphatic signal invisible).

Example 173:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1188)

Followed General procedure J, using ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1179).13C R (151 MHz, DMSO) δ 170,47, 156,25, 136,56, 133,51, 130,39, 129,03, 128,77, 127,82, 126,95, 126,18, 125,69, 124,37, 122,57, 114,29, 64,79, 55,73, 50,52, 42,20, 37,68, 33,44, 30,61, 21,02 (one aromatic signal invisible).

Example 174:3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1189)

Followed General procedure J, using methyl ester 3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1181).13C NMR (151 MHz, DMSO) δ 173,70, 142,32, 138,38, 133,37, 130,49, 128,73, 128,01, 127,68, 126,75, 126,32, 125,64, 125,54, 123,72, 122,60, 56,03, 50,85, 43,18, 35,25, 31,87, 30,49, 29,85, 22,43 (two signals invisible).

Example 175:hydrochloride 3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1190)

Followed General procedure J, using methyl ester 3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1183).13C NMR (151 MHz, DMSO) δ 173,64, 141,55, 138,53, 133,88, 133,34, 130,17, 128,91, 128,88, 128,10, 126,96, 126,73, 126,11, 125,53, 124,62, 122,36, 55,50, 50,35, 42,42, 36,83, 35,13, 33,11, 30,01, 29,78, 20,48.

Example 176:3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1191)

Followed General procedure J, using methyl ester 3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1182).13C NMR (75 MHz, DMSO) δ 173,69, 143,29, 141,05, 138,04, 133,38, 130,84, 128,60, 127,94, 126,78, 126,71, 125,78, 125,54, 125,27, 123,14, 122,85, 56,00, 50,99, 42,49, 39,89, 35,25, 33,25, 33,06, 29,84, 23,58.

Example 177:3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1192)

Followed General procedure J, using methyl ester 3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1184).13C NMR (151 MHz, DMSO) δ 173,72, 142,67, 139,63, 138,24, 133,36, 130,64, 128,67, 127,99, 127,19, 126,69, 126,03, 125,53, 125,45, 123,40, 122,74, 56,27, 51,09, 42,92, 40,90, 35,24, 31,90, 30,70, 29,85, 22,88.

Example 178:ethyl ester {3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1193/1194/1195/1196)

Followed General procedure, using 3-(2-ethoxy-2-oksidoksi)phenylboronic acid. A mixture of four diastereomers:1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), to $ 7.91 (DD, 1H), of 7.75 (DD, 2H), 7,58-7,42 (m, 3H), 7,21-was 7.08 (m, 1H), 6,88-6,62 (m, 3H), 4,74-and 4.68 (m, 2H), 4,70-4,58 (m, 1H), 4,21-4,08 (m, 2H), 3,40-to 2.74 (m, 2H), 2,34-of 1.30 (m, 9H), 1,26-of 1.13 (m, 3H). Four diastereoisomers were separated by preparative chiral HPLC on a column Chiralpak AD-H 250×20 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with mixture of 2-propanol:heptane:NEt3:CH3COOH(90:10:0,1:0,1); consumption = 17,0 ml/min Diastereoisomer 1 (connection 1193): RT = 21,65. The diastereoisomer 2 (connection 1194): RT = 24,65. The diastereoisomer 3 (connection 1195): RT = 45,89. The diastereoisomer of 4 (connection 1196): RT = 52,85.

Example 179:ethyl ester of 3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1197/1198/1198/1200)

Followed General procedure, using 3-(2-ethoxycarbonylethyl)phenylboronic acid. A mixture of 4 diastereomers:1H NMR (300 MHz, DMSO) δ 8.34 per-8,24 (m, 1H), of 7.96-7,86 (m, 1H), of 7.75 (DD, 2H), 7,58-the 7.43 (m, 3H), 7,20-6,92 (m, 4H), 4,71-4,59 (m, 1H), 4,08-3,95 (m, 2H), 3,36-of 2.93 (m, 2H), 2,87-a 2.71 (m, 2H), 2,63 is 2.51 (m, 2H), 2,32-1,32 (m, 9H), 1,20-of 1.07 (m, 3H). Four diastereoisomer was shared by preparative chiral HPLC on a column Chiralpak AD-H 250×20 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with a mixture of n-heptane:ethanol:NEt :CH3COOH(80:20:0,1:0,1); consumption = 17,0 ml/min Diastereoisomer 1 (connection 1197): RT = 7,38. The diastereoisomer 2 (connection 1198): RT = a 9.09. The diastereoisomer 3 (connection 1199): RT = 10,01. The diastereoisomer of 4 (connection 1200): RT = 14,56.

Example 180:hydrochloride {3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1201)

Followed General procedure J, using ethyl ester {3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1196).1H NMR (300 MHz, DMSO) δ of 10.25-9,81 (m, 1H), of 9.55-of 9.21 (m, 1H), 8.30 to (d, 1H), 8,10-to 7.95 (m, 3H), 7.68 per-rate of 7.54 (m, 3H), 7,15 (t, 1H), 6,78-of 6.65 (m, 3H), 5,39 at 5.27 (m, 1H), 4,60 (s, 2H), 3,74-3,63 (m, 1H), 3,59-of 3.42 (m, 1H), 2,52-of 2.34 (m, 1H), 2,23-2,12 (m, 1H), 2,10-to 1.98 (m, 1H), 1,90 by 1.68 (m, 5H), 1,59-of 1.42 (m, 1H).

Example 181:{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1202)

Followed General procedure J, using ethyl ester {3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1193).1H NMR (300 MHz, DMSO) δ of 8.27 (d, 1H), 7,95 (d, 1H), 7,84 (t, 2H), to 7.61-7,47 (m, 3H), to 7.09 (t, 1H), 6,70-6,59 (m, 3H), 4,93 (K, 1H), 4,42 (s, 2H), 3,32-is 3.08 (m, 2H), 2.05 is-to 1.61 (m, 5H), 1.56 to of 1.30 (m, 4H).

Example 182:{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1203)

Followed General procedure J, using ethyl ester {3-[3-(1-naphthalene-1-yl is thylamino)cyclopentyl]phenoxy}acetic acid (compound 1194). 1H NMR (300 MHz, DMSO) δ compared to 8.26 (d, 1H), 7,98-to $ 7.91 (m, 1H), 7,83 (t, 2H), 7,60-7,47 (m, 3H), 7,10 (t, 1H), 6,79-6,70 (m, 2H), 6,69-of 6.61 (m, 1H), 4.92 in (K, 1H), 4,42 (s, 2H), 3,20-of 3.06 (m, 1H), 2,86-a 2.71 (m, 1H), 2,23-of 2.09 (m, 1H), 1,90 was 1.43 (m, 8H).

Example 184:hydrochloride 3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1204)

Followed General procedure J, using ethyl ester {3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1195).1H NMR (300 MHz, DMSO) δ 10,14 (sh, 1H), 9,51 (sh, 1H), 8.30 to (d, 1H), 8,09-to 7.95 (m, 3H), 7,70-7,53 (m, 3H), 7,20 (m, 1H), 6,91-to 6.80 (m, 2H), 6,77 of 6.68 (m, 1H), 5.40 to-5,23 (m, 1H), with 4.64 (s, 2H), 3,61-3,39 (m, 1H), 2,96-was 2.76 (m, 1H), 2,23-of 1.78 (m, 6H), 1,72 (d, 3H).

Example 183:3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1205)

Followed General procedure J, using the ethyl ester of 3-{3-[3-(1-naphthalene~1 ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1199).1H NMR (300 MHz, DMSO) δ 8,40-8,23 (m, 1H), 7,99-7,86 (m, 1H), 7,85-to 7.67 (m, 2H), to 7.61-7,41 (m, 3H), 7,21-6,85 (m, 4H), 4,76-of 4.57 (m, 1H), 3,28-of 3.06 (m, 2H), 2,85-to 2.65 (m, 2H), 2,13-of 1.29 (m, 9H).

Example 185:3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1206)

Followed General procedure J, using the ethyl ester of 3-{3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}-propionic acid (with the Association 1197) 1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), of 7.96-7,87 (m, 1H), 7,76 (DD, 2H), 7,56-the 7.43 (m, 3H), 7,20-to 6.95 (m, 4H), 4,67 (K, 1H), is 3.08 vs. 2.94 (m, 1H), 2,78 (t, 3H), 2,54 at 2.45 (m, 2H), 2,22-of 2.08 (m, 1H), 1,92 to 1.31 (m, 8H).

Example 186:3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1207)

Followed General procedure J, using the ethyl ester of 3-{3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1198).1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), 7,92 (DD, 1H), 7,79 (d, 1H), 7,73 (d, 1H), EUR 7.57-the 7.43 (m, 3H), 7,17-7,07 (m, 1H),? 7.04 baby mortality-6,92 (m, 3H), 4,69 (K, 1H), 3.27 to of 3.07 (m, 2H), 2,74 (t, 2H), 2,50-to 2.41 (m, 2H), 2,08-1,84 (m, 3H), 1,64 of 1.28 (m, 6H).

Example 187:hydrochloride 3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1208)

Followed General procedure J, using the ethyl ester of 3-{3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1200). The product was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ 12,11 (sh, 1H), 10,15 (sh, 1H), 9,46 (sh, 1H), 8.30 to (d, 1H), 8,10-of 7.96 (m, 3H), 7,69-7,56 (m, 3H), 7,20 (m, 1H), 7,10-7,01 (m, 3H), 5,32 (s, 1H), 3,69 (DD, 1H), 3,55-to 3.41 (m, 2H), 3.00 and-to 2.85 (m, 1H), 2,78 (t, 2H), 2,50 (DD, 1H), 2,23 by 1.68 (m, 8H).

Preparation of 5:3-(4-itfinal)cyclohexane-1-it.

It is astory 1,4-diadesol (1.0 g, 3.0 mmol) in 6 ml of dry THF was added chloride Isopropylamine (2 M in THF) at -30°C. the Reaction mixture was stirred for 1 hour at -20°C. Meanwhile, LiCl (26 mg, 0.61 mmol), CuI (58 mg, 0.30 mmol) and TMSCl (329 mg, 3.0 mmol) was added to a solution of 2-cyclohexen-1-it (291 mg, 3.0 mmol) in dry THF (3 ml) and the resulting solution was added to the Grignard solution. The reaction mixture was stirred for another hour at -20°C, then slowly warmed up to K.T. within hours and finally extinguished saturated NH4Cl (aq.) and was extracted with diethyl simple ether. The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (PE-EtOAc 100:0 to 80:20), receiving specified in the header of the connection.

Example 188:[3-(4-itfinal)cyclohexyl]-(1-naphthalene-1-retil)amine (compound 1209)

To a solution of 3-(4-itfinal)cyclohexane-1-it (preparation 5) (5.0 g, and 16.7 mmol) in 15 ml dry DCE was added AcOH (1.20 g, 20 mmol), NaBH(OAc)3(4,96 g and 23.4 mmol) and (+)-(R)-1-naphthalene-1-ylethylamine (2.85 g, and 16.7 mmol) and the mixture was stirred over night at K.T. After adding NaHCO3the mixture was extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (PE-EtOAc 100:0 to 75:25), receiving two faction is, each consisted mainly of a single diastereoisomer. The less polar fraction was founded specified in the header connection.13C NMR (75 MHz, DMSO) δ 147,07, 142,36, 136,65, 133,43, 130,79, 129,09, 128,56, 126,39, 125,56, 125,49, 125,10, 123,03, 122,91, 90,81, 51,00, 50,04, 38,58, 36,51, 32,97, 28,90, 24,52, 20,18.

Example 189:1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}pyrrolidin-2-on (compound 1210)

3-(4-Itfinal)cyclohexane-1-he (compound 1209) (150 mg, 0.33 mmol), 2-pyrrolidone (0.40 mmol), glycine (5 mg, 0.07 mmol), K3PO4(176 mg, 0.83 mmol) and CuI (3 mg, of 0.017 mmol) suspended in 3 ml dry dioxane and heated in a microwave oven at 130°C for 8 hours. The mixture was extracted with ethyl acetate and the organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was purified by chromatography, getting mentioned in the title compound as a solid substance.13C NMR (75 MHz, DMSO) δ 173,34, 142,88, 142,38, 137,15, 133,45, 130,83, 128,58, 126,59, 126,39, 125,59, 125,53, 125,12, 123,05, 122,92, 119,25, 50,87, 50,04, 47,97, 38,82, 36,38, 33,38, 32,12, 28,95, 24,53, 20,28, 17,33.

Example 190:3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxazolidin-2-on (compound 1211)

3-(4-Itfinal)cyclohexane-1-he (compound 1209) (150 mg, 0.33 mmol), 2-oxazolidinone (0.40 mmol, 1.2 equiv.) glycine (5 mg, 0.07 mmol), K3PO4(176 mg, 0.83 mmol) and CuI ( mg, of 0.017 mmol) suspended in 3 ml dry dioxane in an argon atmosphere and heated at 120°C for 35 hours. The mixture was extracted with ethyl acetate and the organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was purified by chromatography, getting mentioned in the title compound in the form of butter.13C NMR (75 MHz, DMSO) δ 154,80, 142,50, 142,34, 136,04, 133,44, 130,82, 128,56, 126,83, 126,38, 125,56, 125,50, 125,09, 123,02, 122,90, 117,87, 61,26, 50,88, 50,03, 44,67, 38,80, 36,28, 33,37, 28,93, 24,49, 20,26.

Example 191:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}ndimethylacetamide (connection 1212)

3-(4-Itfinal)cyclohexane-1-he (compound 1209) (150 mg, 0.33 mmol), ndimethylacetamide (0.40 mmol, 1.2 equiv.) glycine (5 mg, 0.07 mmol), K3PO4(176 mg, 0.83 mmol) and CuI (3 mg, of 0.017 mmol) suspended in 3 ml dry dioxane in an argon atmosphere and heated at 120°C for 35 hours. The mixture was extracted with ethyl acetate and the organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was purified by chromatography, getting mentioned in the title compound in the form of butter.13C NMR (75 MHz, DMSO) δ 167,85, 142,41, 141,95, 136,86, 133,49, 130,87, 128,60, 126,61, 126,42, 125,60, 125,55, 125,13, 123,08, 122,95, 118,87, 50,95, 50,11, 38,92, 36,40, 33,44, 29,02, 24,55, 23,82, 20,35.

Example 192:4-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydropyran-4-ol (connected to the e 1213)

To a solution of 3-(4-itfinal)cyclohexane-1-she (compound 1209) (455 mg, 1 mmol) in dry THF (5 ml) was added chloride Isopropylamine (1 ml of 2 M solution in THF) at -10°C and the resulting mixture was stirred at -10°C 0°C for 4 hours. A solution of tetrahydro-4H-Piran-4-it (150 mg, 1.5 mmol) in 0.5 ml of dry THF was added and the reaction mixture was stirred another hour at 0°C and K.T. during the night. After quenching with NH4Cl mixture was extracted with ethyl acetate, then dried (Na2SO4), filtered and concentrated under reduced pressure. Chromatography (EtOAc) gave specified in the title compound in the form of oil.13C NMR (75 MHz, DMSO) δ 146,84, 145,25, 142,40, 133,46, 130,83, 128,58, 126,40, 126,07, 125,59, 125,54, 125,13, 124,42, 123,04, 122,93, 68,67, 63,07, 50,87, 50,06, 38,89, 38,31, 36,53, 33,30, 29,02, 24,50, 20,31.

Example 193:[3-(4-imidazol-1-ylphenyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1214)

3-(4-Itfinal)cyclohexane-1-he (compound 1209) (150 mg, 0.33 mmol), imidazole (0.40 mmol, 1.2 equiv.) glycine (5 mg, 0.07 mmol), K3PO4(176 mg, 0.83 mmol) and CuI (3 mg, of 0.017 mmol) suspended in 3 ml dry dioxane in an argon atmosphere and heated at 120°Cwithin 35 hours. The mixture was extracted with ethyl acetate and the organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The residual oil was purified XP is matography, getting listed in the title compound in the form of butter.13C NMR (75 MHz, DMSO) δ 146,12, 142,37, 135,32, 134,58, 133,44, 130,82, 129,55, 128,58, 127,83, 126,41, 125,59, 125,52, 125,12, 123,02, 122,91, 120,17, 117,92, 50,91, 50,03, 38,68, 36,49, 33,23, 28,89, 24,52, 20,23.

Example 194:1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}Cyclopentanol (connection 1215)

To a solution of 3-(4-itfinal)cyclohexane-1-she (compound 1209) (125 mg, 0.27 mmol) in dry THF (4 ml) was added chloride Isopropylamine (0,27 ml of 2 M solution in THF) at -20°C and the mixture was stirred at -20°C -10°C for 2 hours, after which was added Cyclopentanone (34 mg, 0.41 mmol) in 0.2 ml of THF. The mixture was stirred at the same temperature for further 30 minutes, then slowly heated until K.T. during the night. After quenching water NH4Cl mixture was extracted with ethyl acetate, and the organic phase was dried, filtered and concentrated under reduced pressure. Chromatography (EtOAc-PE) gave specified in the title compound in the form of oil.13C NMR (75 MHz, DMSO) δ 145,51, 144,83, 142,35, 133,44, 130,82, 128,57, 126,39, 125,81, 125,57, 125,51, 125,10, 124,86, 123,02, 122,90, 81,17, 50,85, 50,05, 41,48, 41,45, 38,88, 36,53, 33,36, 29,01, 24,48, 23,51, 20,30.

Example 194:1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}Etalon (connection 1216)

To a solution of 3-(4-itfinal)cyclohexane-1-she (compound 1209) (200 mg, 0.44 mmol) in dry THF (5 ml) was added chloride Isopropylamine (2 M in THF) at -30°Spoke stirring for 45 min at -30°C → -15°C was added a solution of N-methoxy-N-methylacetamide (49 mg, 0.48 mmol) in THF (2 ml). The reaction mixture was stirred a further 30 min at -20°C-15°C and then warmed up to 0°C for 15 min, the Reaction mixture was extinguished with the help of NH4Cl (aq.) and were extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (PE-EtOAc 100:0 to 50:50) gave specified in the header of the connection.13C NMR (75 MHz, DMSO) δ 197,29, 152,96, 142,37, 134,49, 133,45, 130,80, 128,58, 128,09, 126,82, 126,43, 125,60, 125,52, 125,14, 123,08, 122,93, 51,06, 50,11, 38,38, 37,09, 32,81, 28,92, 26,46, 24,52, 20,16.

Example 195:hydrochloride 4-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydropyran-4-ol (compound 1217)

4-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydro-Piran-4-ol (compound 1213) was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.13C NMR (75 MHz, DMSO) δ 147,31, 142,53, 133,86, 133,35, 130,24, 128,93, 128,87, 127,00, 126,09, 125,50, 124,67, 122,31, 68,72, 63,05, 51,97, 50,25, 38,29, 35,33, 33,63, 31,08, 26,00, 20,73, 19,34.

Example 196:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanol (compound 1218)

To a solution of 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056) (0.50 g, of 1.34 mmol) in dry THF (5 ml) was added to the complex of borane-THF (1 M in THF, to 5.35 mmol) at -78°C. P is a promotional mixture was slowly heated to 0°C for 1.5 hours and then defended with K.T. throughout the night. After cooling in a bath with ice, the mixture is extinguished with water, diluted aqueous NaHCO3and was extracted with diethyl simple ether. The combined organic extracts were dried over MgSO4and concentrated under reduced pressure. Chromatography (EtOAc-PE 1:1) gave specified in the title compound in the form of oil.13C NMR (75 MHz, MeOH) δ 147,33, 142,64, 139,93, 135,58, 132,69, 130,06, 128,25, 128,10, 127,88, 126,94, 126,66, 126,42, 124,36, 123,81, 65,12, 52,01, 51,93, 39,65, 38,69, 34,52, 30,84, 24,26, 21,78.

Example 197:1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}cyclobutanol (connection 1219)

To a solution of 3-(4-itfinal)cyclohexane-1-she (compound 1209) (250 mg, 0.55 mmol) in dry THF (1 ml) in an argon atmosphere at -78°C was added n-BuLi (0,37 ml of 1.6 M in THF). The obtained red solution was stirred for 2 min at the same temperature and then was added dropwise cyclobutanone (45 μl, of 0.60 mmol). Immediately light yellow solution was stirred at -78°C for 10 min before quenching with 1,2 M KH2PO4(aq.). The mixture was extracted with ethyl acetate, and the organic phase was dried and concentrated in vacuum. Chromatography (EtOAc-PE 1:1) gave specified in the header of the connection.13C NMR (75 MHz, DMSO) δ 145,25, 144,81, 142,39, 133,44, 130,82, 128,57, 126,39, 126,03, 125,59, 125,53, 125,12, 124,60, 123,04, 122,92, 74,88, 50,86, 50,05, 38,88, 37,05, 36,58, 33,33, 29,01, 24,51, 20,30, 12,59.

Example 198:diethyl ester -{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}malonic acid (compound 1220)

3-(4-Itfinal)cyclohexane-1-he (compound 1209) (0,80 g of 1.76 mmol), and diethyl ester of malonic acid (0.56 g, to 3.52 mmol), CsCO3(0,86 g of 2.64 mmol), CuI (33 mg, 0.18 mmol) and 2-hydroxybiphenyl (60 mg, 0.35 mmol) were mixed in dry THF (5 ml) in an argon atmosphere and heated at 100°C for 8 days. The mixture was diluted with water and extracted with ethyl acetate. The organic phase is washed with saturated salt solution, dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (PE-EtOAc 100:0 to 50:50) gave specified in the title compound in the form of solid, which was subjected to recrystallization in ethanol.13C NMR (75 MHz, DMSO) δ 167,91, 147,02, 142,35, 133,44, 130,82, 130,05, 128,88, 128,55, 126,56, 126,39, 125,58, 125,51, 125,11, 123,02, 122,92, 61,10, 56,27, 50,92, 50,02, 38,78, 36,63, 33,11, 28,91, 24,48, 20,25, 13,74.

Example 199:ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid (compound 1221)

To a solution of ester diethyl 2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}malonic acid (compound 1220) (100 mg, 0.20 mmol) in DMSO (5 ml) was added water (3.6 mg, 0.20 mmol) and LiCl (17 mg, 0.41 mmol). The resulting mixture was heated at 150°C overnight, diluted with water and was extracted with EtOAc. The organic phase is washed with saturated salt solution, dried over Na2S 4and concentrated under reduced pressure. Chromatography (PE-EtOAc 50:50) gave specified in the title compound in the form of oil.13C NMR (75 MHz, DMSO) δ 171,14, 145,78, 142,40, 133,45, 131,40, 130,83, 128,89, 128,57, 126,53, 126,39, 125,59, 125,53, 125,12, 123,05, 122,93, 60,06, 50,91, 50,05, 39,81, 38,89, 36,59, 33,27, 28,96, 24,52, 20,29, 13,98.

Example 200:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid (compound 1222)

A solution of ester ethyl {4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid (compound 1221) (400 mg) in methanol (5 ml) was treated with 2 M NaOH in methanol and was stirred for 1 day at K.T. Methanol was removed under reduced pressure. The residual aqueous phase was acidified with 4 M aqueous HCl and was extracted with ethyl acetate. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (MeOH-CH2Cl220:80) gave specified in the title compound in the form of solids.13C NMR (75 MHz, DMSO) δ 172,72, 144,65, 133,42, 132,24, 130,63, 129,05, 128,70, 127,24, 126,41, 126,07, 125,52, 125,45, 123,63, 122,71, 50,69, 40,27, 37,09, 36,18, 32,57, 27,93, 23,24, 19,97.

Example 201:3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxetan-3-ol (compound 1223)

To a solution of 3-(4-itfinal)cyclohexane-1-she (compound 1209) (3.7 g, 8.1 mmol) in dry THF (25 ml) in an argon atmosphere was added chloride from ropeline (8,1 ml of 2 M solution in THF) at -30°C - -40°C. the Reaction mixture was heated to -10°C-0°C and stirred this temperature for 5 hours, was added a solution of 3-oxetanone (0.50 g, 6,9 mmol) in THF (3 ml). Stirring is continued for the next 2 hours at the same temperature. The reaction mixture is finally, slowly heated until K.T. during the night, extinguished with NH4Cl and extracted with ethyl acetate. The organic phase is washed with saturated salt solution, dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (CHCl3-MeOH 100:0 to 95:5) gave specified in the title compound in the form of oil.13C NMR (75 MHz, DMSO) δ 146,09, 142,40, 141,30, 133,47, 130,83, 128,59, 126,41, 126,34, 125,59, 125,54, 125,13, 124,31, 123,07, 122,94, 85,13, 73,78, 50,96, 50,13, 38,89, 36,62, 33,27, 29,03, 24,53, 20,31.

Example 202:{3-[4-(3-Torosyan-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1224)

To a solution of 3-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxetan-3-ol in CH2Cl2(connection 1223) (5 ml) was added TRIFLUORIDE diethylaminoethyl (0,21 ml). The mixture was stirred for ½ hour, extinguished NaHCO3and was extracted with CH2Cl2. The organic phase was dried over Na2SO4, filtered and concentrated under reduced pressure. Chromatography (MeOH-CH2Cl21:99) gave specified in the title compound in the form of oil.13C NMR (5 MHz, DMSO) δ 148,01, 142,39, 134,93, 134,62, 133,47, 130,83, 128,59, 126,88, 126,42, 125,61, 125,54, 125,14, 124,45, 124,35, 123,07, 122,94, 97,01, 94,31, 81,42, 81,08, 50,98, 50,09, 38,71, 36,73, 33,11, 28,97, 24,53, 20,25.

Example 203:{3-[4-(3-amino-3-methylbut-1-inyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1225)

To a solution of 3-(4-itfinal)cyclohexane-1-she (compound 1209) (150 mg, 0.33 mmol) in diethylamine (3 ml, degassed by bubbling argon through the solution for 5 min) was added PdCl2(Ph3P)2(15 mg) and CuI (8 mg). The mixture was degirolami with argon for another 5 min, cooled to 0°C was added 2-methyl-3-Butin-2-yl-amine (137 mg, of 1.65 mmol). The reaction mixture was stirred at 0°C for 30 min and K.T. within 1 hour and was extracted with EtOAc. The organic phase was dried (Na2SO4), filtered and concentrated under reduced pressure. Chromatography (EtOAc) gave specified in the title compound in the form of oil.13C NMR (126 MHz, CDCl3) δ 146,47, 141,93, 133,09, 130,37, 130,17, 127,84, 125,90, 125,82, 124,69, 124,31, 122,61, 122,41, 119,69, 78,93, 51,09, 49,97, 44,76, 39,10, 37,90, 36,30, 32,16, 31,32, 29,36, 23,45, 19,73.

General procedure L

The acid chloride (41 μmol), N-hydroxy-4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1051, 49 mmol) and CDI (45 mmol) in 150 μl of DMF was which when K.T. during the night. Additional CDI (45 μmol) in 50 μl of DMF was added and the reaction mixture was heated at 115°C during the night. Product sight of the Ali preparative HPLC.

Example 204:{3-[4-(5-cyclopropyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1226)

Followed General procedure L using cyclopropanecarboxylate.1H NMR (600 MHz, DMSO) δ 8,35 (d, 1H), to 7.93 (d, 1H), 7,83-7,74 (m, 4H), 7,56-7,47 (m, 3H), 7,18 (d, 2H), 4,74 (s, 1H), is 3.08 3.00 for (m, 1H), 2,93-of 2.86 (m, 1H), 2,41 to 2.35 (m, 1H), 1.93 and-1,82 (m, 1H), 1,81-1,72 (m, 2H), 1,70-to 1.63 (m, 1H), 1.56 to to 1.39 (m, 6H), 1,36-of 1.24 (m, 3H), 1,20-to 1.14 (m, 2H).

Example 205:{3-[4-(5-cyclopentyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1227)

Followed General procedure L using cyclopentanecarboxylate.1H NMR (600 MHz, DMSO) δ at 8.36 (d, 1H), to 7.93 (d, 1H), 7,82 (d, 2H), 7,80 (d, 1H), 7,76 (d, 1H), 7,55-of 7.48 (m, 3H), 7,20 (m, 2H), 4,74 (s, 1H), 3,47 (dt, 1H), is 3.08-a 3.01 (m, 1H), 2,92-2,87 (m, 1H), 2,16-of 2.09 (m, 2H), 1,92 of-1.83 (m, 3H), 1,81-1,72 (m, 4H), 1,72-to 1.63 (m, 3H), 1.56 to of 1.40 (m, 6H), 1,37 of 1.28 (m, 1H).

Example 206:{3-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1228)

Followed General procedure L using acetylchloride.1H NMR (600 MHz, DMSO) δ at 8.36 (d, 1H), to 7.93 (d, 1H), 7,82 (d, 2H), 7,79 (d, 1H), 7,76 (d, 1H), 7,56-7,47 (m, 3H), 7,19 (d, 2H), 4,71 (s, 1H), is 3.08 3.00 for (m, 1H), 2.91 in-2,84 (m, 1H), 2,64 (s, 3H), 1.93 and of-1.83 (m, 1H), 1,81-to 1.61 (m, 3H), 1.56 to to 1.37 (m, 6H), 1,35-of 1.27 (m, 1H).

Example 207:{3-[4-(5-isopropyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1229)

Followed General procedure L using isobutyrate.1H NMR (600 MHz, DMSO) δ at 8.36 (d, 1H), to 7.93 (d, 1H), 7,83 (d, 2H), to 7.77 (d, 1H), 7,76 (d, 1H), 7,56-7,47 (m, 3H), 7,19 (d, 2H), 4,74-of 4.66 (m, 1H), 3,34 (m, 1H, overlapped with water signal), is 3.08-a 3.01 (m, 1H), 2.91 in-2,86 (m, 1H), 1.93 and-1,83 (m, 1H), 1,82-of 1.73 (m, 2H), 1.70 to of 1.64 (m, 1H), of 1.44 (d, 3H), 1,55-of 1.26 (m, 4H), to 1.37 (d, 6H).

Example 208:{3-[4-(5-tert-butyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1230)

Followed General procedure L, 2,2-dimethylpropionic.1H NMR (600 MHz, DMSO) δ at 8.36 (d, 1H), to 7.93 (d, 1H), 7,83 (d, 2H), 7,79 (d, 1H), 7,76 (d, 1H), 7,56-7,47 (m, 3H), 7,20 (m, 2H), 4,70 (s, 1H), is 3.08-a 3.01 (m, 1H), 2.91 in-2,85 (m, 1H), 1,94 of-1.83 (m, 1H), 1,81-of 1.73 (m, 2H), 1.70 to to 1.63 (m, 1H), 1,57-to 1.38 (m, 6H), of 1.44 (s, 9H), 1,36-of 1.26 (m, 1H).

Example 209:{3-[4-(5-cyclohexyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1231)

Followed General procedure L using cyclohexanecarbonitrile.1H NMR (600 MHz, DMSO) δ at 8.36 (d, 1H), to 7.93 (d, 1H), 7,82 (d, 2H), 7,79 (d, 1H), 7,76 (d, 1H), 7,56-7,47 (m, 3H), 7,19 (d, 2H), 4.72 in (K, 1H), 3,13-a 3.01 (m, 2H), 2.91 in-2,86 (m, 1H), 2,10-2,02 (m, 2H), 1.93 and of-1.83 (m, 1H), 1,81-1,72 (m, 4H), 1.70 to and 1.56 (m, 4H), 1,55-of 1.36 (m, 8H), 1,35 is 1.23 (m, 2H).

Example 210:(3-{4-[5-(3-methylbutyl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1232)

Followed General procedure L using 4-methylpentanoate.1H NMR (60 MHz, DMSO) δ at 8.36 (d, 1H), to 7.93 (d, 1H), 7,83 (d, 2H), 7,80 (d, 1H), to 7.77 (d, 1H), 7,56-of 7.48 (m, 3H), 7,20 (m, 2H), 4,77-4,71 (m, 1H), is 3.08-a 3.01 (m, 1H), 3.00 and-2,96 (m, 2H), 2,92-is 2.88 (m, 1H), 1,92 of-1.83 (m, 1H), 1,82-at 1.73 (m, 2H), 1,71 is 1.58 (m, 4H), 1,57-of 1.40 (m, 6H), 1,37-of 1.29 (m, 1H), to 0.92 (d, 6H).

Example 211:5-(3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}-[1,2,4]oxadiazol-5-ylmethyl)imidazolidin-2,4-dione (compound 1233)

Followed General procedure L using (2,5-dioxoimidazolidin-4-yl)acetylchloride.1H NMR (600 MHz, DMSO) δ 10,83 (sh, 1H), at 8.36 (d, 1H), with 8.05 (d, 1H), 7,94 (DD, 1H), 7,83 (d, 2H), 7,80 (d, 1H), to 7.77 (d, 1H), 7,56-of 7.48 (m, 3H), 7,21 (d, 2H), 4,74 (K, 1H), 4,59-4,56 (m, 1H), 3,43 (DD, 1H), 3,38 (DD, 1H), is 3.08-to 3.02 (m, 1H), 2,92-is 2.88 (m, 1H), 1.93 and of-1.83 (m, 1H), 1,82-of 1.73 (m, 2H), 1,71-of 1.65 (m, 1H), 1,58-of 1.40 (m, 6H), 1,36-of 1.29 (m, 1H).

Example 212:(3-{4-[5-(4-methoxazole-5-yl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1234)

Followed General procedure L using 4-methoxazole-5-carbonylchloride.1H NMR (600 MHz, DMSO) δ is 8.75 (s, 1H), at 8.36 (d, 1H), 7,97-7,89 (m, 3H), 7,79 (d, 1H), to 7.77 (d, 1H), 7,56-of 7.48 (m, 3H), 7,25 (d, 2H), 4.75 V-4,69 (m, 1H), 3,11 totaling 3.04 (m, 1H), 2,92-2,87 (m, 1H), 2,58 (s, 3H), 1,89 (DD, 1H), 1,78 (s, 2H), 1,68 (d, 1H), 1,57-of 1.40 (m, 6H), 1,32 (t, 1H).

Example 213:(3-{4-[5-(2,5-dimethyloxazole-4-yl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1235)

Followed General procedure L using 2.5-dimethyloxazole-4-carbonylchloride.1H NMR (600 MG IS, DMSO) δ at 8.36 (d, 1H), 7,94 (DD, 1H), of 7.90 (d, 2H), 7,79 (d, 1H), to 7.77 (d, 1H), 7,56-of 7.48 (m, 3H), of 7.23 (d, 2H), 4,71 (K, 1H), 3,11-to 3.02 (m, 1H), 2.91 in-2,86 (m, 1H), 2,73 (s, 3H), 2.49 USD (s, 3H), 1,94-of 1.84 (m, 1H), 1,82-of 1.74 (m, 2H), 1,71-of 1.65 (m, 1H), 1,57-of 1.40 (m, 6H), 1,36-of 1.27 (m, 1H).

General procedure M

To a solution of cycloalkanones (400 μmol) in 400 μl of DME was added Bronevoy acid (480 μmol, 1.2 EQ.), (COD)Rh(1,4-dihydrogen)BF4(1 mol.%) 100 μl ofDME and LiOH (4 mol.%) 600 μl of water. After stirring the mixture overnight at 50°C the solvent was removed in vacuum. The crude intermediate ketone was dissolved in DCE containing acetic acid (1.2 EQ.). (+)-(R)-1-naphthalene-1-ylethylamine (1 EQ.) in DCE was added followed by the addition of NaBH(OAc)3(1.2 equiv.) The mixture was which during the night when K.T., filtered and the solvents were removed in vacuum. The residue was re-dissolved in 750 μl of DMSO and purified by HPLC.

Example 214:2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionitrile (connection 1236/1237)

Followed General procedure M using 4-(2-cyanoprop-2-yl)phenylboronic acid and 2-cyclohexen-1-it. Specified in the title compound was purified by chromatography on 20 g of silica gel with a gradient from 0 to 60% EtOAc in n-heptane, flow rate 30 ml/min Connection 1236 (1 isomer, less polar, RT ~11 min).13C NMR (75 MHz, DMSO) δ 146,84, 142,38, 138,59, 133,47, 130,84, 128,60, 127,05, 126,42, 125,62, 125,54, 125,15, 124,80, 124,69, 123,04, 122,94, 50,88, 49,99, 38,75, 36,56, 36,17, 33,17, 28,94, 28,26, 4,52, 20,25. Connection 1237 (1 isomer, more polar, RT ~13 min):13C NMR (75 MHz, DMSO) δ 146,76, 142,14, 138,61, 133,39, 130,84, 128,55, 127,18, 126,39, 125,62, 125,50, 125,10, 124,85, 124,66, 122,92, 122,80, 50,11, 49,30, 36,44, 36,28, 36,15, 33,36, 30,74, 28,24, 24,40, 20,50.

Example 215:2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1238)

To a solution of 2-methyl-2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionitrile (connection 1236) in MeOH (0,09 M, y ml) was added 28% aq. NaOH (y/2 ml). The mixture was heated to the boil with the return of phlegmy within 3 days. MeOH was removed under reduced pressure. The residue was taken in water and was added 4 n aq. HCl to pH=5. The precipitate was collected, washed with water and dried in vacuum,getting listed at the beginning of the connection.13C NMR (126 MHz, DMSO) δ 177,53, 145,26, 142,13, 133,45, 130,83, 128,58, 126,44, 126,38, 125,63, 125,53, 125,22, 125,15, 123,03, 122,92, 50,77, 49,95, 45,22, 38,78, 36,48, 33,22, 28,88, 26,29, 24,40, 20,25.

Example 216:2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1239)

To a solution of 2-methyl-2-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionitrile (connection 1237) in MeOH (0,09 M, y ml) was added 28% aq. NaOH (y/2 ml). The mixture was heated to the boil with the return of phlegmy within 3 days. MeOH was removed under reduced pressure. The residue was taken in water and was added 4 n aq. HCl to pH=5. The precipitate was collected, industrial is Ali water and dried in vacuum, getting listed at the beginning of the connection.1H NMR (600 MHz, DMSO) δ 8,31 (d, 1H), 7,94 (d, 1H), 7,85-7,73 (m, 2H), 7,52 (t, 3H), 7,22-6,99 (m, 4H), 5,10-a 4.53 (m, 1H), 3,05 (S.T., 1H), 2,84 (sh, 1H), 1,90-of 1.26 (m, 17H).

Example 217:[3-(4-methanesulfonyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1240)

Followed General procedure M using 4-(methanesulfonyl)bendovervideo acid and 2-cyclohexen-1-it. Connection 1240 (1 isomer): LC-MS (method B): RT = 4,14, [M+H]+= 408,1.1H NMR (600 MHz, DMSO) δ 8.30 to (d, 1H), of 7.96-7,88 (m, 1H), 7,80 (d, 2H), to 7.77 (d, 1H), 7,72 (d, 1H), 7,55-7,44 (m, 5H), 4,71 (K, 1H), 3,18 (s, 3H), 3,23 is 3.15 (m, 1H), 2,82 (s, 1H), 1,86-of 1.73 (m, 3H), 1,64-of 1.56 (m, 1H), 1,51 is 1.34 (m, 7H).

Example 218:methyl ester 2-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1241)

Followed General procedure M using 3-fluoro-4-(methoxycarbonyl)bendovervideo acid and 2-cyclohexen-1-it. Connection 1241: (1 isomer): LC-MS (method B): RT = of 4.44, [M+H]+= 406,1.1H NMR (600 MHz, DMSO) δ 8.30 to (d, 1H), 7,93-7,89 (m, 1H), to 7.77 (dt, 2H), 7,72 (d, 1H), 7,52 was 7.45 (m, 3H), 7,18 (DD, 2H), 4,71 (K, 1H), 3,83 (s, 3H), 3,17 (t, 2H), 2,81 (s, 1H), 1.85 to 1,72 (m, 3H), 1,58 (d, 1H), 1,50-to 1.32 (m, 7H).

Example 219:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanol (compound 1242)

Followed General procedure M using 4-(hydroxymethyl)phenylboronic acid and 2-cyclohexen-1-about the. LC-MS (method B): RT = 4,21, [M+H]+= 360,2 (mixture of 2 isomers).

Example 220:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}methanesulfonamide (connection 1243)

Followed the General procedure M and using (4-methanesulfonylaminoethyl)baronova acid and 2-cyclohexen-1-it. Connection 1243 (1 isomer): LC-MS (method B): RT = 4,27, [M+H]+= 437,1.1H NMR (600 MHz, DMSO) δ a 8.34 (d, 1H), 7,92 (DD, 1H), to 7.77 (DD, 2H), 7,55-7,47 (m, 3H), 7,44 (t, 1H), 7,16 (d, 2H), 7,01 (d, 2H), 4,69 (K, 1H), 4,06 (d, 2H), 2,99-only 2.91 (m, 1H), 2,88 is 2.80 (m, 4H), 1,90 and 1.80 (m, 1H)that is 1.73 (DD, 2H), 1,65-to 1.60 (m, 1H), 1,51-1,25 (m, 7H).

Example 221:{3-[4-(morpholine-4-sulfonyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1244/1245)

Followed General procedure M using 4-N-morpholinylformamidine acid and 2-cyclohexen-1-it. Connection 1244 (mixture of 2 isomers): LC-MS (method B): RT = 4,32, [M+H]+= 479,2. Connection 1245 (mixture of 2 isomers): LC-MS (method B): RT = 4,36, [M+H]+= 479,1.

Example 222:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}ndimethylacetamide (connection 1246/1247)

Followed the General procedure M and using (4-acetamidomethyl)baronova acid and 2-cyclohexen-1-it. Connection 1246 (mixture of 2 isomers): LC-MS (method B): RT = 4.09 to, [M+H]+= 401,1, [M+HCOO]-= 445,2. Connection 1247 (mixture of 3 isomers): LC-MS (method B): RT = 4,12, [M+H]+= 401,1, [M+HCOO] = 445,0.

Example 223:methyl ester of 3-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1248)

Followed General procedure M using 2-fluoro-4-methoxycarbonylpropionyl acid and 2-cyclohexen-1-it. Connection 1248 (mixture of 2 isomers): LC-MS (method B): RT = 4,56, [M+H]+= 406,0.

Example 224:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanesulfonamide (connection 1249/1250)

Followed General procedure M using 4-(methanesulfonamido)phenylboronic acid and 2-cyclohexen-1-it. Connection 1249 (mixture of 2 isomers): LC-MS (method B): RT = 4,24, [M+H]+= 423,1, [M-H]-= 421,1. Connection 1250 (mixture of 2 isomers): LC-MS (method B): RT = 4,34, [M+H]+= 423,2, [M-H]-= 421,0.

Example 225:N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanesulfonamide (1251 connection)

Followed General procedure M using 3-(methylsulfonylamino)phenylboronic acid and 2-cyclohexen-1-it. Connection 1251 (mixture of 2 isomers): LC-MS (method B): RT = 4,29, [M+H]+= 423,1, [M-H]-= 421,0.

Example 226:N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzosulfimide (connection 1252/1253)

Followed General procedure M using 4-(2-hydroxyethylsulphonic)phenylboron the first acid and 2-cyclohexen-1-it. Connection 1252 (mixture of 2 isomers): LC-MS (method B): RT = 4,11, [M+H]+= 453,1, [M-H]-= 451,0. Connection 1253 (mixture of 4 isomers): LC-MS (method B): RT = 4,22, [M+H]+= 453,1, [M-H]+= 451,0.

Example 227:3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1254)

Followed General procedure M using 2-methoxycarbonylaminophenyl acid and 2-cyclohexenone. The intermediate ester hydrolyzed following General procedureJ. preparative HPLC gave specified in the title compound in the form of oil and as a single isomer. LC-MS (method B): RT = 4,32, [M+H]+= 402,1.1H NMR (600 MHz, DMSO) δ of 8.28 (d, 1H), to $ 7.91 (d, 1H), to 7.77 (d, 1H), 7,71 (d, 1H), 7,53 was 7.45 (m, 3H), 7,15-7,00 (m, 4H), 4.75 V-of 4.66 (m, 1H), 3,05-2,96 (m, 1H), 2,87-of 2.72 (m, 3H), 1,84-to 1.67 (m, 3H), 1,62-and 1.54 (m, 1H), 1,47 to 1.31 (m, 7H), (2 hydrogen atom invisible under signal of water in the 3.2 to 3.6 ppm)

Example 228:{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenoxy}acetic acid (compound 1255)

Followed General procedure M using 4-(2-ethoxy-2-oksidoksi)bendovervideo acid and 2-cyclohexenone. The intermediate ester hydrolyzed following General procedure J. preparative HPLC gave specified in the title compound in the form of oil and as a single isomer. LC-MS (method B): RT = 4,22, [M+H]+= 404,1.1H NMR (600 MHz, DMSO) δ 8,29 (d, 1H), 7,92 (d, 1H, for 7.78 (d, 1H), 7,76-7,71 (m, 1H), 7,54-7,46 (m, 3H), 7,17-of 6.99 (m, 2H), 6.87 in-only 6.64 (m, 2H), 4,79-4,70 (m, 1H), 3,06-to 2.94 (m, 1H), 2,87-2,77 (m, 1H), 1,84-to 1.67 (m, 3H), 1,62-and 1.54 (m, 1H), 1,50 to 1.31 (m, 7H).

Example 229:[3-(4-methanesulfonyl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine (compound 1256/1257)

Followed General procedure M using 4-(methanesulfonyl)bendovervideo acid and 2-cyclopenten-1-it. Connection 1256 (mixture of 2 isomers): LC-MS (method B): RT = 4,22, [M+H]+= 394,1. Connection 1257 (mixture of 3 isomers): LC-MS (method B): RT = 4,24, [M+H]+= 394,1.

Example 230:N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}methanesulfonamide (connection 1258/1259)

Followed General procedure M using 3-(methylsulfonylamino)phenylboronic acid and 2-cyclopenten-1-it. Connection 1258 (mixture of 2 isomers): LC-MS (method B): RT = 4,27, [M+H]+= 409,1, [M-H]+= 407,0. Connection 1259 (mixture of 3 isomers): LC-MS (method B): RT = 4,29, [M+H]+= 409,1, [M-H]+= 407,1.

Example 231:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}ndimethylacetamide (connection 1260/1261)

Followed General procedure M using 4-acetaminophenydrocodone acid and 2-cyclopenten-1-it. Connection 1260 (mixture of 2 isomers): LC-MS (method B): RT = 4,16, [M+H]+= 373,2, [M+HCOO]-= 417,1. Connection 1261 (mixture of isomers): LC-MS (method B): RT = 4,19, [M+H]+= 373,2, [M+HCOO]-= 417,1.

Note the p 232: N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzyl}ndimethylacetamide (connection 1262/1263)

Followed the General procedure M and using (4-acetamidomethyl)baronova acid and 2-cyclopenten-1-it. Connection 1262 (mixture of 2 isomers): LC-MS (method B): RT = 4,12, [M+H]+= 387,1, [M+HCOO]-= 431,0. Connection 1263 (mixture of 4 isomers): LC-MS (method B): RT = 4,14, [M+H]+= 387,1, [M+HCOO]-= 431,0.

Example 233:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzyl}methanesulfonamide (connection 1264/1265)

Followed the General procedure M and using (4-methanesulfonylaminoethyl)baronova acid and 2-cyclopenten-1-it. Connection 1264 (mixture of 2 isomers): LC-MS (method B): RT = 4,24, [M+H]+= 423,1, [M+HCOO]-= 467,0. Connection 1265 (mixture of 4 isomers): LC-MS (method B): RT = 4,27, [M+H]+= 423,1, [M+HCOO]-= 467,0.

Example 234:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}methanesulfonamide (connection 1266/1267)

Followed General procedure M using 4-(methanesulfonamido)phenylboronic acid and 2-cyclopenten-1-it. Connection 1266 (mixture of 2 isomers): LC-MS (method B): RT = 4.26 deaths, [M+H]+= 409,0, [M-H]+= 407,0. Connection 1267 (mixture of 3 isomers): LC-MS (method B): RT = 4,27, [M+H]+= 409,0, [M-H]+= 406,9.

Example 235:[3-(4-methanesulfonyl)cycloheptyl]-((R)-1-naphthalene-1-retil)Amin (the connection is giving 1268)

Followed General procedure M using 4-(methanesulfonyl)bendovervideo acid and 2-cyclohepten-1-it. Connection 1268 (mixture of isomers): LC-MS (method B): RT = 4,34, [M+H]+= 422,1.

Example 236:methyl ester 2-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzoic acid (compound 1269)

Followed General procedure M using 3-fluoro-4-(methoxycarbonyl)bendovervideo acid and 2-cyclohepten-1-it. Connection 1269 (mixture of isomers): LC-MS (method B): RT = 4,57, [M+H]+= 420,1.

Example 237:N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanesulfonamide (connection 1270)

Followed General procedure M using 3-(methylsulfonylamino)phenylboronic acid and 2-cyclohepten-1-he, the Connection 1270 (mixture of isomers): LC-MS (method B): RT = to 4.41, [M+H]+= 437,1, [M-H]+= 435,0.

Example 238:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}ndimethylacetamide (connection 1271/1272)

Followed General procedure M using 4-acetaminophenydrocodone acid and 2-cyclohepten-1-it. Connection 1271 (mixture of isomers): LC-MS (method B): RT = 4,27, [M+H]+= 401,1, [M+HCOO]-= 445,2. Connection 1272 (mixture of isomers): LC-MS (method B): RT = 4,32, [M+H]+= 401,2, [M+HCOO]-= 445,2.

Example 239:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)C is cloepfil]benzyl}ndimethylacetamide (connection 1273/1274)

Followed the General procedure M and using (4-acetamidomethyl)baronova acid and 2-cyclohepten-1-it. Connection 1273 (mixture of 2 isomers): LC-MS (method B): RT = 4,24, [M+H]+= 415,2, [M+HCOO]-= 459,1. Connection 1274 (mixture of 2 isomers): LC-MS (method B): RT = 4.26 deaths, [M+H]+= 415,2, [M+HCOO]-= 459,2.

Example 240:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzyl}methanesulfonamide (connection 1275/1276)

Followed the General procedure M and using (4-methanesulfonylaminoethyl)baronova acid and 2-cyclohepten-1-it. Connection 1275 (mixture of isomers): LC-MS (method B): RT = 4,37, [M+H]+= 451,1, [M+HCOO]-= 495,2. Connection 1276 (mixture of isomers): LC-MS (method B): RT = 4,39, [M+H]+= 451,1, [M+HCOO]-= 495,0.

Example 241:ethyl ester {4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenoxy}acetic acid (compound 1277)

Followed General procedure M using 4-(2-ethoxy-2~oksidoksi)phenylboronic acid and 2-cyclohepten-1-it. Connection 1277 (mixture of 2 isomers): LC-MS (method B): RT = 4,66, [M+H]+ = 446,2.

Example 242:methyl ester 3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}propionic acid (compound 1278/1279)

Followed General procedure M using 4-(2-methoxycarbonylethyl)phenylboronic acid and 2-eclogite-1-it. Connection 1278 (mixture of 2 isomers): LC-MS (method B): RT = 4,66, [M+H]+= 430,2. Connection 1279 (mixture of 3 isomers): LC-MS (method B): RT = 4,66, [M+H]+= 430,1.

Example 243:N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanesulfonamide (connection 1280/1281)

Followed General procedure M using 4-(methanesulfonamido)phenylboronic acid and 2-cyclohepten-1-it. Connection 1280 (mixture of isomers): LC-MS (method B): RT = 4,36, [M+H]+= 437,1, [M-H]-= 434,9. Connection 1281 (mixture of isomers): LC-MS (method B): RT = 4,37, [M+H]+= 437,1, [M-H]-= 434,9.

Example 244:{3-[4-(morpholine-4-sulfonyl)phenyl]cycloheptyl}-((R)-1-naphthalene-1-retil)amine (compound 1282)

Followed General procedure M using 4-(4-morpholinylcarbonyl)phenylboronic acid and 2-cyclohepten-1-it. Connection 1282 (mixture of isomers): LC-MS (method B): RT = 4,47, [M+H]+= 493,2.

Example 245:{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanol (compound 1283)

Followed General procedure M using 4-(hydroxymethyl)phenylboronic acid and 2-cyclohepten-1-it. Connection 1283 (mixture of isomers): LC-MS (method B): RT = 4,32, [M+H]+= 374,2.

General procedure N

To a solution of 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056, 1.5 mmol) in 6 ml of dry DMF was added CDI (1.8 m is ol). After stirring the solution for 4 hours at K.T. was added the alcohol (22 mmol, 15 equiv.) and stirring was continued over night at K.T. the Solvent was removed under reduced pressure, and the residue was purified by chromatography.

Example 246:methyl ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1284)

Followed General procedure N, using methanol. Chromatography (CH2Cl2-MeOH 100:0 to 95:5) gave specified in the header of the connection.13C NMR (75 MHz, DMSO) δ 166,13, 153,14, 147,17, 142,50, 133,54, 130,88, 129,04, 128,64, 126,99, 126,48, 125,66, 125,60, 125,20, 123,16, 123,03, 51,86, 51,24, 50,22, 38,57, 37,15, 32,82, 29,04, 24,64, 20,26.

Example 247:ethyl ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1285)

Followed General procedure N, using ethanol. Chromatography (CH2Cl2-MeOH 100:0 to 97:3) gave specified in the title compound in the form of oil.13C NMR (75 MHz, DMSO) δ 165,58, 153,03, 142,44, 133,50, 130,85, 128,97, 128,60, 127,26, 126,90, 126,44, 125,61, 125,55, 125,16, 123,11, 122,98, 60,35, 51,16, 50,15, 38,51, 37,12, 32,85, 28,98, 24,59, 20,21, 14,10.

Example 248:the dihydrochloride of 2-morpholine-4-Eletropaulo of ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1286)

Followed General procedure N, using N-(2-hydroxyethyl)orfelin. Chromatography (CH2Cl2-MeOH 100:0 to 97:3) gave an oil which was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.13C NMR (75 MHz, DMSO) δ 165,07, 150,89, 133,85, 133,32, 130,24, 129,60, 128,92, 128,84, 126,99, 126,89, 126,09, 125,50, 124,80, 122,29, 63,07, 58,87, 54,40, 51,88, 51,25, 50,42, 35,91, 33,45, 30,81, 25,66, 20,94, 19,28.

Example 249:hydrochloride of 2-(2-methoxyethoxy)of ester ethyl 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1287)

Followed General procedure N, using onomatology simple ether of diethylene glycol. Chromatography (CH2Cl2-MeOH 100:0 to 80:20) gave an oil which was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ 9,54 (sh, 2H), 8,35 (d, 1H), to 8.20 (d, 1H), 8,03-7,94 (m, 2H), a 7.85 (d, 2H), 7,60 (dt, 3H), 7,32 (d, 2H), 5,56-5,42 (m, 1H), to 4.41-4,34 (m, 2H), 3,78-3,70 (m, 2H)and 3.59 (DD, 2H), 3.46 in (DD, 2H), 3,36-3,26 (m, 1H), 3,24 (s, 3H), 3,19-of 3.07 (m, 1H), 2,12-to 1.37 (m, 11H).

Example 250:hydrochloride of 2-[2-(2-methoxyethoxy)ethoxy]ethyl complex ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1288)

Followed General procedure N, using onomatology simple ether of triethylene glycol. Chromatography(CH 2Cl2-MeOH 100:0 to 80:20) gave an oil which was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ 9,48 (s, 2H), 8,35 (d, 1H), 8,17 (d, 1H), 7,99 (t, 2H), 7,86 (d, 2H), 7.62mm (DD, 3H), 7,31 (d, 2H), 5,57-5,42 (m, 1H), 4,42-to 4.33 (m, 2H), 3,78-3,70 (m, 2H), 3,62 of 3.56 (m, 2H), 3,55-3,47 (m, 4H), 3.45 points-to 3.36 (m, 2H), 3.33 and-3,26 (m, 1H), 3,20 (s, 3H), 3,18-is 3.08 (m, 1H), 2,11-to 1.37 (m, 11H).

Example 251:hydrochloride of 2-[2-(2-ethoxyethoxy)ethoxy]ethyl complex ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1289)

Followed General procedure N, using monotropy simple ether of triethylene glycol. Chromatography (CH2Cl2-MeOH 100:0 to 80:20) gave an oil which was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ for 9.47 (sh, 2H), 8.34 per (d, 1H), 8,15 (d, 1H), 7,99 (t, 2H), 7,86 (d, 2H), to 7.61 (DD, 3H), 7,31 (d, 2H), 5,48 (sh, 1H), 4,43-to 4.33 (m, 2H), 3,79-3,70 (m, 2H), 3,63 is 3.57 (m, 2H), 3,56-3,47 (m, 4H), of 3.46 3.21-in (m, 5H), 3,20-to 3.09 (m, 1H), 2,09 to 1.37 (m, 11H), of 1.05 (t, 3H).

Example 252:hydrochloride of 2,3-dihydroxypropyl of ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1290)

Followed General procedure N, using D-α,β-isopropylidene glaze is in. Intermediate acetonide was purified by chromatography (CH2Cl2-MeOH 100:0 to 80:20)to give oil, which was dissolved in EtOAc and treated with HCl in dioxane (4 M). After adding diethyl simple ether the precipitate was filtered, getting listed at the beginning of the connection.13C NMR (75 MHz, DMSO) δ 165,53, 150,34, 133,82, 133,32, 130,24, 129,28, 128,91, 127,63, 127,01, 126,88, 126,09, 125,49, 124,70, 122,28, 69,28, 66,11, 62,51, 51,93, 50,42, 35,89, 33,40, 30,81, 25,80, 20,83, 19,29.

Example 253:hydrochloride tetrahydrofuran-2-Eletropaulo of ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1291)

Followed General procedure N, using tetrahydrofurfurylamine alcohol. Chromatography (CH2Cl2-MeOH 100:0 to 80:20) gave an oil which was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ 9,45 (sh, 2H), 8,35 (d, 1H), 8,16 (d, 1H), 7,99 (t, 2H), a 7.85 (d, 2H), to 7.61 (dt, 3H), 7,32 (d, 2H), 5,56-5,42 (m, 1H), or 4.31-4,10 (m, 3H), 3,79 (dt, 1H), of 3.73-3,63 (m, 1H), 3,36-is 3.21 (m, 1H), 3,20-is 3.08 (m, 1H), 2,12-to 1.37 (m, 15H).

General procedure O

[Rh(R-BINAP)(nbd)]BF4or [Rh(S-BINAP)(nbd)]BF4, (Tani, K.; Yamagata, T.; Akutagawa, S.; Kumobayashi, H.; Taketomi, T.; Takaya, H.; Miyashita, A.; Noyori, R.; Otsuka, S.J. Am. Chem. Soc.1984,106,5208) (0.03 mmol) and arylboronic acid (1.5 mmol) was added into the flask of 25 ml, containing a magnetic core of mascalchi diaphragm valve. The flask was flushed with argon and downloaded it water 1,4-dioxane (6/1, 3 ml). Then was added triethylamine (1.5 mmol) and 2-cyclopenten-1-he (1.0 mmol). The mixture was stirred for 6 h at 25°C. was Added a saturated salt solution, and the mixture was extracted with ethyl acetate. If necessary, the product was purified by chromatography on silica gel.

Preparation 6:3R-(4-hydroxyphenyl)Cyclopentanone

Followed the General procedure Of using 4-hydroxyphenylarsonic acid and [Rh(R-BINAP)(nbd)]BF4.1H NMR (300 MHz, DMSO) δ 9,19 (s, 1H), 7,10 (d, 2H), 6,70 (d, 2H), 3.33 and-3,19 (m, 1H), 2,44 (d, 1H), 2,34 with 2.14 (m, 4H), 1.91 a to 1.76 (m, 1H).

Example 254:4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenol (compound 1292)

Followed General procedure A, using 3-(4-hydroxyphenyl)Cyclopentanone (preparation 6). Two diastereoisomer obtained were divided by preparative chiral HPLC on a column Chiralpak AD-H 250×20 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with a mixture of n-heptane:ethanol:NEt3:CH3COOH(75:25:0,1:0,1); consumption = 17,0 ml/min Connection 1292: RT = 17,15.1H NMR (300 MHz, DMSO) δ 8.34 per-8,24 (m, 1H), of 7.96-7,87 (m, 1H), 7,82-to 7.68 (m, 2H), EUR 7.57-the 7.43 (m, 3H), 7.03 is-6,94 (m, 2H), 6,67-6,59 (m, 2H), 4,67 (K, 1H), 3,05-of 2.93 (m, 1H), 2,80-of 2.66 (m, 1H), 2.13 and of 1.99 (m, 1H), 1,88-1,52 (m, 4H), 1.41 to 1,22 (m, 4H).

General procedure P:

4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenol (Obedinenie 1292) (0.1 mmol) was weighed in a vessel and dissolved in 1 ml of acetonitrile. To this solution was added allylbromide or carbamoylated (0,12-0,15 mmol) and K2CO3(0.15 to 0.2 mmol). The vessel was sealed and the reaction mixture was heated up to 80°C and was stirred for 16 hours. The conversion was monitored by LC/MS. The reaction mixture was filtered through a pad of celite and concentrated in vacuum. The crude product was purified preparative HPLC.

Example 255:ethyl ester 2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1293)

Followed General procedure R using ethyl ester 2-bromoethanol acid as allylbromide. A mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ 8,33 is 8.25 (m, 1H), to $ 7.91 (DD, 1H), to 7.77 (d, 1H), 7,72 (d, 1H), 7,56-7,44 (m, 3H), 7,11 (d, 2H), 6.75 in (d, 2H), 4,71-br4.61 (m, 2H), 4,13 (K, 2H), 3,05-of 2.93 (m, 1H), 2,85-2,70 (m, 1H), 2,17-2,01 (m, 1H), 1.93 and-of 1.55 (m, 7H), 1.41 to of 1.26 (m, 4H), of 1.18 (t, 3H), of 0.96 (t, 3H).

Example 256:2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1294)

Followed General procedure J, using ethyl ester 2-{4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid. A mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ of 8.25 (d, 1H), 8,00-to 7.93 (m, 1H), 7,87 (t, 2H), 7,63-of 7.48 (m, 3H), 7,09-7,00 (m, 1H), 6,97 (d, 1H), 6.75 in (DD, 2H), 5,12-to 4.98 (m, 1H), 4,42-to 4.33 (m, 1H), 3,22-of 3.06 (m, 1H), 2,83-to 2.65 (m, 1H), 2,22-to 2.06 (m, 1H), 2,03-of 1.42 (m, 10H)to 0.97 (t, 3H).

Example 257:2-{4-[1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid (compound 1295)

Followed General procedure R using ethyl 2-bromopropionate as allylbromide. The intermediate ester hydrolyzed following General procedureJ. a Mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ 8,24 (d, 1H), 8,02-7,74 (m, 3H), 7,63-7,44 (m, 3H), 7,00 (DD, 2H), 6,82-only 6.64 (m, 2H), of 5.05-4,88 (m, 1H), 4,60-of 4.44 (m, 1H), 3,15-2,96 (m, 1H), 2.82 from 2.63 in (m, 1H), 2,20-2,02 (m, 1H), 1,96 of 1.28 (m, 11H).

Example 258:3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}dihydrofuran-2-on (compound 1296)

Followed General procedure R using α-bromo-butyrolactone as allylbromide. A mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), 7,95 (DD, 1H), a 7.85 (d, 1H), 7,80 to 7.75 (m, 1H), 7,62-7,47 (m, 3H), 7,21-7,11 (m, 2H), 6,99-of 6.90 (m, 2H), 5,26 (DD, 1H), 4,87 (K, 1H), 4,42 (TD, 1H), 4,34-4,22 (m, 1H), 3,17 (DK, 1H), 2,92-to 2.67 (m, 2H), 2,21 (DDT, 2H), 1,96 is 1.60 (m, 4H), 1,55-of 1.40 (m, 4H).

Example 259:(S)-{3R-[4-(2-ethoxyethoxy)phenyl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine (compound 1297)

Followed General procedure R using 2-ethoxyethylene as allylbromide.1H NMR (300 MHz, DMSO) δ 8,33 is 8.25 (m, 1H), 7,98-a 7.92 (m, 1H), a 7.85 (d, 1H), 7,82-7,76 (m, 1H), 7,60-of 7.48 (m, 3H), 7,15-7,07 (m, 2H), 6.87 in-6,79 (m, 2H), 4,89 (K, 1H), was 4.02 (DD, 2H), 3,70-3,63 (m, 2H), 3,48 (K, 2H), 3,24-3,11 (m, 1H), 2,89-of 2.72 (m, 1H), 2,24 and 2.13 (m, 1H), 1,92-to 1.59 (m, 4H), 1,55-of 1.41 (m, 4H), of 1.12 (t, 3H).

Example 260:ethyl ester of 3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}prop is about acid (compound 1298)

Followed General procedure R using ethyl 3-bromopropionate as allylbromide.1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), 7,94 (DD, 1H), 7,82 (d, 1H), to 7.77-7,72 (m, 1H), to 7.59-7,47 (m, 3H), 7,11 (d, 2H), PC 6.82 (d, 2H), 4,79 (K, 1H), 4,14 (t, 2H), 4.09 to (K, 3H), 3,17 totaling 3.04 (m, 1H), 2,88 was 2.76 (m, 1H), by 2.73 (t, 2H), 2.21 are of 2.08 (m, 1H), 1,92-of 1.57 (m, 4H), 1,49 is 1.34 (m, 4H), of 1.18 (t, 3H).

Example 261:4-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxymethyl}benzonitrile (connection 1299)

Followed General procedure R using 4-cyanobenzeneboronic as allylbromide.1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), to 7.93 (DD, 1H), 7,89 for 7.78 (m, 3H), of 7.75 (d, 1H), 7.62mm (d, 2H), 7,58-7,46 (m, 3H), 7,13 (d, 2H), 6.90 to (d, 2H), by 5.18 (s, 2H), 4,78 (K, 1H), 3,16-3,03 (m, 1H), 2,89-a 2.71 (m, 1H), 2,19-2,07 (m, 1H), 1,91-of 1.57 (m, 4H), 1,47-of 1.33 (m, 4H).

Example 262:(S)-((R)-1-naphthalene-1-retil)-{3R-[4-(pyridine-3-ylethoxy)phenyl]cyclopentyl}amine (compound 1300)

Followed General procedure R using hydrogen bromide 3-(methyl bromide)pyridine as allylbromide.1H NMR (300 MHz, DMSO) δ 8,65 (d, 1H), 8,53 (DD, 1H), 8,29 (d, 1H), 7,97-of 7.90 (m, 1H), 7,88-7,79 (m, 2H), of 7.75 (d, 1H), to 7.59-7,47 (m, 3H), 7,44-7,38 (m, 1H), 7,14 (d, 2H), 6,93 (d, 2H), 5,10 (s, 2H), 4,79 (K, 1H), 3,16 totaling 3.04 (m, 1H), 2,89-a 2.71 (m, 1H), 2.21 are of 2.08 (m, 1H), 1,91-of 1.56 (m, 4H), 1,48 is 1.34 (m, 4H).

Example 263:(S)-((R)-1-naphthalene-1-retil)-{3R-[4-(2-pyrazole-1-ylethoxy)phenyl]cyclopentyl}amine (compound 1301)

Followed a total of proced the re P, using 1-(2-bromacil)-1H-pyrazole as allylbromide.1H NMR (300 MHz, DMSO) δ of 8.28 (d, 1H), 7,94 (DD, 1H), 7,82 (d, 1H), of 7.75 (DD, 2H), to 7.59-7,47 (m, 3H), 7,46-the 7.43 (m, 1H), 7,10 (d, 2H), 6,79 (d, 2H), 6,23 (t, 1H), 4,81 (K, 1H), 4,46 (t, 2H), 4,27 (t, 2H), 3,19-3,05 (m, 1H), 2,88-2,70 (m, 1H), 2.21 are of 2.08 (m, 1H), 1,92-of 1.55 (m, 4H), 1,49-of 1.32 (m, 4H).

Example 264:(S)-(3R-{4-[2-(1H-indol-3-yl)ethoxy]phenyl}cyclopentyl)-((R)-1-naphthalene-1-retil)amine (compound 1302)

Followed General procedure R using 3-(2-bromacil)indole as allylbromide.1H NMR (300 MHz, DMSO) δ 10,86 (s, 1H), 8,29 (d, 1H), 7,97-to $ 7.91 (m, 1H), 7,82 (d, 1H), of 7.75 (d, 1H), to 7.61-7,46 (m, 4H), 7,34 (d, 1H), 7.23 percent (d, 1H), 7,15-6,94 (m, 4H), 6,85 (d, 2H), 4,81 (K, 1H), 4,16 (t, 2H), 3,17-a 3.06 (m, 3H), 2,88-a 2.71 (m, 1H), 2.21 are of 2.09 (m, 1H), 1,92-of 1.56 (m, 4H), 1,49 is 1.35 (m, 4H).

Example 265:hydrochloride of 2-methyl-2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid (compound 1303)

Followed General procedure R using ethyl 2-bromo-2-methylpropionate as allylbromide. The intermediate ester hydrolyzed following General procedureJ, acid to neutral. Neutral acid was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting listed at the beginning of the connection.1H NMR (300 MHz, DMSO) δ 12,96 (sh, 1H), 10,18-10,02 (sh, 1H), 9,49 was 9.33 (sh, 1H), 8.30 to (d, 1H), 8,08-7,94 (m, 3H), 7,69-rate of 7.54 (m, 3H), 7,12 (d, 2H), 6.75 in (d, 2H), 5,38-5,24 (m, 1H), 3,53-,43 (m, 1H), 2,98-and 2.79 (m, 1H), 2,46 of-2.32 (m, 1H), 2,20-2,04 (m, 1H), 1,97-of 1.65 (m, 7H), of 1.47 (s, 6H).

Example 266:4-hydroxy-2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1304)

Followed General procedure J, using 3-{4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}dihydrofuran-2-on (compound 1296). A mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ 8,24 (d, 1H), 8,02-7,94 (m, 1H), 7,93-of 7.82 (m, 2H), 7,63-7,49 (m, 3H), 7,08-of 6.90 (m, 2H), 6,80 is 6.67 (m, 2H), 5,16-5,02 (m, 1H), 4,58-4,47 (m, 1H), 3,66-to 3.50 (m, 2H), 3,22-is 3.08 (m, 2H), 2,83-2,65 (m, 1H), 2,22-of 1.84 (m, 4H), 1,81-of 1.44 (m, 7H).

Example 267:hydrochloride of 2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid (compound 1305)

Followed General procedure R using ethyl 2-bromopropionate as allylbromide. The intermediate ester hydrolyzed following General procedureJ, acid to neutral. Neutral acid was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting mentioned in the title compound as a mixture of two isomers.1H NMR (300 MHz, DMSO) δ 9,65 (sh, 1H), 9,27 (sh, 1H), 8.30 to (d, 1H), 8,02 (t, 2H), to 7.93 (d, 1H), 7,71-7,56 (m, 3H), 7,13 (d, 2H), 6,80 (d, 2H), 5.40 to-the 5.25 (m, 1H), a 4.83-4,71 (m, 1H), 3,63 is-3.45 (m, 1H), 2,92 (s, 1H), 2,53 to 2.35 (m, 1H), 2,14-of 1.85 (m, 3H), at 1.73 (m, 5H), of 1.47 (d, 3H).

Example 268:hydrochloride {4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopen the Il]phenoxy}phenylacetic acid (compound 1306)

Followed General procedure R using ethyl bromophenylacetate as allylbromide. The intermediate ester hydrolyzed using General procedure J. the Product was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting mentioned in the title compound as a mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ 9,65 (sh, 1H), 9,27 (sh, 1H), 8.30 to (d, 1H), 8.07-a of 7.97 (m, 2H), to 7.93 (d, 1H), 7,70-7,56 (m, 3H), 7,13 (d, 2H), 6,80 (d, 2H), 5,39-of 5.26 (m, 1H), 4.75 in (K, 1H), 3,62-3,47 (m, 1H), 2,92 (s, 1H), of 2.51-of 2.36 (m, 1H), 2,13-of 1.85 (m, 3H), 1,80-to 1.63 (m, 5H), of 1.47 (d, 3H).

Example 269:2-methyl-1-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propan-2-ol (compound 1307)

To a solution of ester ethyl {4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1180) (150 mg, 360 μmol) in dry THF (2 ml) was added bromide Metalmania (3.0 M in THF, 0.6 ml) at -78°C. After stirring for 5 hours at -78°C to -40°C, the reaction mixture was extinguished aqueous NaHCO3and were extracted with ethyl acetate. The organic phase was concentrated in vacuum and purified HPLC, getting listed at the beginning of the connection.13C NMR (75 MHz, DMSO) δ 157,00, 141,09, 137,34, 133,38, 130,78, 128,60, 127,59, 126,74, 125,76, 125,53, 125,25, 123,13, 122,83, 114,20, 76,07, 68,52, 56,45, 51,23, 42,52, 41,92, 32,12, 31,41, 26,53, 23,65.

Example 270:3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine is)cyclopentyl]phenoxymethyl}pentane-3-ol (compound 1308)

To a solution of ester ethyl {4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1180) (150 mg, 360 μmol) in dry THF (2 ml) was added bromide of etermine of (1.0 M in THF, 718 μl) at -78°C. After stirring for 2.5 hours at this temperature, additional bromide of etermine added (360 μl) and the reaction mixture was stirred for another hour before quenching aqueous NaHCO3and extraction with ethyl acetate. The organic phase was concentrated in vacuum and purified HPLC, getting listed at the beginning of the connection.13C NMR (75 MHz, DMSO) δ 156,92, 142,08, 137,61, 133,39, 130,88, 128,56, 127,60, 126,44, 125,59, 125,53, 125,12, 122,96, 122,91, 114,14, 72,12, 71,80, 56,60, 51,34, 42,54, 42,47, 32,21, 31,89, 28,68, 24,18, 7,40.

Example 271:4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl ester dimethylcarbinol acid (compound 1309)

Followed General procedure R using N,N-dimethylcarbamoyl.1H NMR (300 MHz, DMSO) δ 8.30 to (d, 1H), to $ 7.91 (DD, 1H), of 7.75 (DD, 2H), EUR 7.57-the 7.43 (m, 3H), 7,21 (d, 2H), 6,97 (d, 2H), 4,67 (K, 1H), to 3.02 (s, 3H), 2,89 (s, 4H), 2,18-to 2.06 (m, 1H), 1.93 and is 1.58 (m, 4H), 1,47-of 1.30 (m, 4H). Signal (1H), probably invisible under signal of water at 3,32 ppm

Example 272:3-ethyl-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}pentane-3-ol (compound 1310)

To a solution of ester methyl 3-{-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1183) (150 mg) in dry THF (2 ml) was slowly added to the bromide of etermine (1.8 ml of 1.0 M solution in THF) at -78°C. The reaction mixture was stirred for 5 hours with slow warming to -40°C. ethyl Acetate was added to the mixture, and the product was purified HPLC.1H NMR (300 MHz, DMSO) δ 8.30 to (d, 1H), 7,97-7,89 (m, 1H), 7,81 (d, 1H), of 7.75 (d, 1H), to 7.59-7,46 (m, 3H), 7,03 (s, 4H), 4.75 in (K, 1H), 3.27 to 3,10 (m, 2H), 2,50-of 2.38 (m, 2H), 2,09-to 1.79 (m, 3H), 1.70 to a 1.46 (m, 4H), 1,45-of 1.30 (m, 8H), of 0.79 (t, 6H).

Example 273:2-methyl-4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}butane-2-ol (compound 1311)

To a solution of ester methyl 3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1183) (150 mg) in dry THF (2 ml) was added bromide Metalmania (0.6 ml of 3M solution in THF) at -78°C. the Reaction mixture was stirred for 5 hours with slow warming to -40°C. ethyl Acetate (0.5 ml) was added and the mixture was purified HPLC, getting listed at the beginning of the connection.13C NMR (75 MHz, DMSO) δ 142,76, 141,00, 140,11, 133,40, 130,77, 128,63, 127,90, 126,81, 126,63, 125,81, 125,54, 125,29, 123,19, 122,84, 68,54, 56,20, 50,83, 45,71, 42,42, 40,71, 33,17, 32,65, 29,68, 29,17, 23,61.

Example 274:3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propane-1,2-diol (compound 1312)

Followed General procedure R using 3-bromo-propane-1,2-diol as allylbromide. Connection 1312 (mixture of 2 isomers): LC-MS (method A): RT = 2,44, [M+H]+= is 406.5.

Example 275:hydrochloride (2-forfinal)-{4-[(1R,3S)-3-((R)-1-naphthalene-1-retirementality]phenoxy}acetic acid (compound 1313)

Followed General procedure R using methyl ester bromo-(2-forfinal)acetic acid as allylbromide. The intermediate ester hydrolyzed following General procedureJ, acid to neutral. Neutral acid was dissolved in ethyl acetate and treated with HCl in dioxane (4 M) and diethyl simple ether. The precipitate was filtered, getting mentioned in the title compound as a mixture of 2 isomers.1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), 8,12 (d, 1H), 8,04-7,94 (m, 2H), to 7.67-to 7.50 (m, 4H), of 7.48 and 7.36 (m, 1H), 7,30-7,19 (m, 2H), 7,14 (d, 2H), to 6.88 (d, 2H), of 5.89 (s, 1H), 5,35-5,22 (m, 1H), 4.53-in was 4.42 (m, 1H), 2,94-and 2.79 (m, 1H), 2,41-of 2.09 (m, 2H), 1.91 a-to 1.67 (m, 7H).

Example 276:formate 2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}ethanol (compound 1314)

To a solution of ester ethyl {4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1180) (180 mg) in dry diethyl simple ether (3 ml) was added LiAlH4(0,52 ml of 1 M solution in THF) at 0°C. After 30 min the reaction mixture was extinguished with water and was purified preparative HPLC, getting mentioned in the title compound in the form of butter.1H NMR (300 MHz, DMSO) δ 8,33-8,24 (m, 2H), 7,98-a 7.92 (m, 1H), a 7.85 (d, 1H), 7,78 (d, 1H), to 7.61-of 7.48 (m, 3H), 7,11 (d, 2H), PC 6.82 (d, 2H), 4,88 (K, 1H), 3,93 (t, 2H), 3,69 (t, 2H), 3,23-3,11 (m, 1H), 2,88-by 2.73 (m, 1H), 2,19 (dt, 1H), 1,92-to 1.59 (m, 4H), 1,55-of 1.40 (m, 4H).

Preparation 7:4-(3-oxocyclohexa is)benzaldehyde

Followed General procedure K using 4-formylphenylboronic acid.13C NMR (75 MHz, DMSO) δ 209,52, 192,53, 151,70, 134,67, 129,75, 127,46, 47,42, 43,72, 40,32, 31,66, 24,80.

General procedure Q

To a solution of 4-(3-oxocyclohexyl)benzaldehyde (0,082 mmol) in DCE (1 ml) was added amine (165 μl of a 0.5 mm solution in DCE) and NaBH(OAc)3(0.24 mmol, 3 EQ.). After stirring the reaction mixture overnight at K.T. was added (+)-(R)-1-naphthalene-1-ylethylamine (0,090 mmol) in 0.5 ml of DCE, and stirring was continued over night at K.T. Solvents were removed in vacuum. The residue was re-dissolved in DMSO and was purified preparative HPLC.

Example 277:(1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}pyrrolidin-2-yl)methanol (compound 1315)

Followed General procedure Q, using (S)-(+)-2-(hydroxymethyl)pyrrolidin. LC-MS (method B): RT = 3,67, [M+HCOO]-= 487,3.

Example 278:1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}pyrrolidin-3-ol (compound 1316)

Followed General procedure Q using (R)-3-hydroxypyrrolidine. LC-MS (method B): RT = 3,67, [M+H]+= 429,2.

Example 279:ethyl ester 1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}piperidine-3-carboxylic acid (compound 1317)

Followed General procedure Q, ispolzuemyy ester piperidine-3-carboxylic acid. LC-MS (method B): RT = 3,86, [M+H]+= 499,3.

Example 280:[3-(4-{[methyl-(tetrahydrofuran-2-ylmethyl)amino]methyl}phenyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1318)

Followed General procedure Q using N-methyltetrahydrofuran. LC-MS (method B): RT = 3,76, [M+H]+= 457,3.

Preparation 8:ethyl ester of 3-[4-((1S)-3-oxocyclopent)phenyl]propionic acid

Followed the General procedure Of using [4-(2-ethoxycarbonylethyl)phenyl]Bronevoy acid and [Rh(S-BINAP)(nbd)]BF4.1H NMR (300 MHz, DMSO) δ 7,26-7,20 (m, 2H), 7,19-7,13 (m, 2H), 4.04 the (K, 2H), 3,43-3,24 (m, 1H), 2,82 (t, 2H), 2.63 in at 2.45 (m, 3H), 2,35-of 2.21 (m, 4H), 1,96-to 1.77 (m, 1H)and 1.15 (t, 3H).

Preparation 9:ethyl ester of 3-[4-((1S,3R)-3-acetoxyacetyl)phenyl]propionic acid

To a solution of ester ethyl 3-[4-(3-oxocyclopent)phenyl]propionic acid (preparation 8) (26,2 g, 100 mmol) in ethanol (300 ml) was added NaBH4(5.7 g, 151 mmol) in portions. The mixture was stirred at K.T. within 1 hour, and then the solvent was removed in vacuum. To the residue was added water, and the mixture was extracted several times with dichloromethane. The combined organic extracts were dried over MgSO4and concentrated in vacuum. To the crude Cyclopentanol (25,7 g, 98,0 mmol) in dry n-hexane (340 ml) was added to ylacetic (340 ml, 50 equiv.) molecular sieves (4Å) and PPL (lipase from porcine pancreas, EC 3.1.1.3, 30,1 units/mg, 20 g). The mixture was stirred in an argon atmosphere for 2 hours, filtered through celite and concentrated under reduced pressure. Chromatography (EtOAc-PE 0:100 to 50:50) and picking up the less polar fractions gave specified in the title compound in the form of oil.1H NMR (300 MHz, DMSO) δ 7,20-to 7.09 (m, 4H), 5,16-of 5.06 (m, 1H), 4.04 the (K, 2H), 3,09-to 2.94 (m, 1H), 2,80 (t, 2H), 2,58 (t, 2H), 2,52-2,39 (m, 1H), 2,04-is 1.51 (m, 8H)and 1.15 (t, 3H).

Preparation of 10:ethyl ester of 3-[4-((1S,3R)-3-hydroxycyclopent)phenyl]propionic acid

To a solution of ester ethyl 3-[4-(3-acetoxyacetyl)phenyl]propionic acid (preparation 9) (23.1 g, 75,9 mmol) in dry ethanol (1.1 l) in an argon atmosphere was added K2CO3(31,5 g, 228 mmol). The mixture was heated at 50-60°C for 3 hours, then filtered through celite and concentrated under reduced pressure. The residue is suspended in water and was extracted with dichloromethane. The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was used without further purification.1H NMR (300 MHz, DMSO) δ 7,17 (d, 2H), 7,11 (d, 2H), br4.61-4,56 (m, 1H), 4,24-to 4.14 (m, 1H), 4.04 the (K, 2H), 2,99-to 2.85 (m, 1H), 2,80 (t, 2H), 2.57 m (t, 2H), 2,32-2,19 (m, 1H), 1,96 is 1.58 (m, 4H), 1,52-to 1.38 (m, 1H), 1,20-of 1.10 (m, 3H).

Preparation 11:ethyl with whom you can ether 3-[4-((1S,3R)-3-methanesulfonylaminoethyl)phenyl]propionic acid

To a solution of ester ethyl 3-[4-(3-hydroxycyclopent)phenyl]propionic acid (preparation 10) (3,16 g, 12.1 mmol) in dry CH2Cl2(30 ml) in an argon atmosphere was added NEt3(3,66 g, 36,1 mmol) and methanesulfonamide (1,38 g, 24,1 mmol) at 0°C. After stirring the resulting solution for 1 hour at 0°C the reaction mixture was extinguished with water and was extracted with CH2Cl2. The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The crude product was used immediately without further purification.1H NMR (300 MHz, DMSO) δ 7,21-to 7.09 (m, 4H), 5,22-5,13 (m, 1H), 4.04 the (K, 2H), 3,17 (s, 3H), 3,13-of 2.93 (m, 1H), of 2.81 (t, 2H), 2,63-2,52 (m, 3H), 2,08-of 1.93 (m, 3H), 1,86-to 1.61 (m, 2H)and 1.15 (t, 3H).

General procedure R

To a suspension of ester ethyl 3-[4-(3-methanesulfonylaminoethyl)phenyl]propionic acid (preparation 11) (1.20 mmol) in propionitrile (3 ml) was added K2CO3(3.6 mmol) and amine (1.20 mmol) and the reaction mixture was heated at 80°C during the night. The mixture was filtered and the filtrate was concentrated under reduced pressure. The product was purified preparative HPLC, 10 → 80% ethyl acetate in hexano.

Example 281:ethyl ester of 3-(4-{(1S,3S)-3-[(R)-1-(4-fluoro-3-methoxyphenyl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1319)

SL is followed General procedure R, using 1-(4-fluoro-3-methoxyphenyl)ethylamine.1H NMR (300 MHz, DMSO) δ 7,22 (DD, 1H), 7,10 (m, 5H), 6,94 (m, 1H), 4,03 (K, 2H), 3,85 (m, 4H), 3.15 in (m, 2H), 2,78 (t, 2H), has 2.56 (t, 2H), 1,99 (m, 2H), 1,78 (m, 1H), 1.70 to about 1.35 (m, 3H), of 1.30 (d, 3H), 1.14 in (t, 3H).

Example 282:ethyl ester of 3-(4-{(1S,3S)-3-[(R)-1-(3-cyanophenyl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1320)

Followed General procedure R using 1-(3-cyanophenyl)ethylamine.1H NMR (300 MHz, DMSO) δ of 7.82 (s, 1H), 7,69 (m, 2H), 7,52 (t, 1H), 7,07 (m, 4H), 4,03 (K, 2H), 3,82 (K, 1H), 3.15 in (m, 1H), 2,98 (m, 1H), 2,78 (t, 2H), by 2.55 (t, 2H), 2,01 (m, 1H), 1.91 a (m, 1H), 1,70 (DDD, 1H), of 1.57 (m, 1H), 1,45 (m, 2H), 1,25 (d, 3H), 1.14 in (t, 3H).

Example 283:ethyl ester of 3-{4-[(1S,3S)-3-((R)-1-benzo[b]thiophene-3-ylethylamine)cyclopentyl]phenyl}propionic acid (compound No. 1321)

Followed General procedure R using 1-benzo[b]thiophene-3-ylethylamine.1H NMR (300 MHz, DMSO) δ 8,03 (DD, 1H), of 7.97 (DD, 1H), 7,65 (s, 1H), 7,38 (m, 2H), was 7.08 (m, 4H), 4,36 (K, 1H), 4,03 (K, 2H), or 3.28 (m, 1H), 3,17 (m, 1H), 2,77 (t, 2H), by 2.55 (t, 2H), 2,00 (m, 2H), of 1.84 (m, 1H), of 1.59 (m, 2H), 1,45 (d, 3H), of 1.40 (m, 1H), 1.14 in (t, 3H).

Example 284:ethyl ester of 3-(4-{(1S,3S)-3-[1-((R)-2,3-dihydrobenzo[1,4]dioxin-6-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1322)

Followed General procedure R using 1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethylamine.1H NMR (300 MHz, DMSO) δ 7,09 (2, 4H), 6,92 (s, 1H), 6,85 (d, 1H), 6,8 (d, 1H), 4,22 (s, 4H), 4,03 (K, 2H), 3,84 (K, 1H), 3.15 in (m, 2H), 2,78 (t, 2H), has 2.56 (t, 2H), 2,00 (m, 2H), of 1.85 (m, 1H), 1,68 (m, 1H), and 1.56 (m, 1H), 1,45 (m, 1H), of 1.30 (d, 3H), 1.14 in (t, 3H),

Example 285:ethyl ester of 3-{4-[(1S,3S)-3-((R)-1-phenylethylamine)cyclopentyl]phenyl}propionic acid (compound 1323)

Followed General procedure R using 1-phenylethylamine.1H NMR (300 MHz, DMSO) δ to 7.3 (m, 4H), 7,22 (TT, 1H), 7,07 (DD, 4H), 4,03 (K, 2H), 3,82 (K, 1H), 3.15 in (m, 1H), 3,05 (m, 1H), 2,77 (t, 2H), by 2.55 (t, 2H), 2,01 (m, 1H), 1.93 and (m, 1H), 1,76 (m, 1H), 1,65-of 1.35 (m, 3H), of 1.29 (d, 3H), 1.14 in (t, 3H).

Example 286:ethyl ester of 3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzofuran-5-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1324)

Followed General procedure R using 1-(2,3-dihydrobenzofuran-5-yl)ethylamine.1H NMR (300 MHz, DMSO) δ 7.18 in (d, 1H), 7,06 (m, 5H), of 6.65 (d, 1H), 4,47 (t, 2H), 4,03 (K, 2H), 3,66 (K, 1H), 3,14 (m, 3H), of 3.00 (m, 1H), 2,78 (t, 2H), has 2.56 (t, 2H), 2,01 (m, 1H), 1,89 (m, 1H), 1,70 (m, 1H), of 1.57 (m, 1H), 1,44 (m, 2H), 1,21 (d, 3H), 1.14 in (t, 3H).

Example 287:hydroformed 3-(4-{1S,3S)-3-[(R)-1-(1H-indol-7-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1325)

Followed General procedure J, using ethyl 3-(4-{3-[1-(1H~indol-7-yl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ 11,20 (s, 1H), 8,32 (s, 1H), 7,46 (d, 1H), 7,35 (m, 1H), 7,20 (m, 1H), was 7.08 (d, 2H),? 7.04 baby mortality (d, 2H), 7,01 (t, 1H), 6,45 (DD, 1H), 4,54 (DD, 1H), 3,23 (m, 1H), 3,18 (m, 1H), 2,74 (t, 2H), the 2.46 (t, 2H), 2,02 (m, 1H),was 1.94 (m, 2H), by 1.68 (m, 2H), 1,49 (d, 3H), of 1.42 (d, 1H).

Example 288:hydroformed 3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzo[1,4]dioxin-5-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1326)

Followed General procedure J, using ethyl 3-(4-{3-[1-(2,3-dihydrobenzo[1,4]dioxin-5-yl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ of 8.25 (s, 1H), 7,11 (d, 2H), was 7.08 (d, 2H), 7,00 (DD, 1H), 6,83 (DD, 1H), 6,76 (DD, 1H), 4,28 (m, 2H), 4,23 (m, 2H), 3,20 (m, 1H), and 3.16 (m, 1H), 2,75 (m, 2H), 2,47 (m, 2H), 2,02 (m, 1H), a 1.96 (m, 1H), of 1.88 (m, 1H), 1,71 (m, 1H), 1,59 (m, 1H), 1,46 (m, 1H), 1,33 (d, 3H).

Example 289:hydroformed 3-(4-{(1S,3S)-3-[(R)-1-(1H-indol-4-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1327)

Followed General procedure J, using ethyl 3-(4-{3-[1-(1H-indol-4-yl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ to 11.28 (s, 1H), with 8.33 (s, 1H), 7,39 (m, 1H), 7,37 (d, 1H), 7,24 (d, 1H),7,14 (m, 1H), to 7.09 (d, 2H), 7,05 (d, 2H), of 6.71 (m, 1H), br4.61 (K, 1H), or 3.28 (m, 1H), 3,23 (m, 1H), 2,75 (t, 2H), 2,47 (t, 2H), 2,00 (m, 3H)and 1.83 (m, 1H), 1,74 (m, 1H), equal to 1.59 (d, 3H), of 1.41 (m, 1H).

Example 290:hydroformed 3-(4-{(1S,3S)-3-[(R)-1-(3-cyanophenyl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1328)

Followed General procedure J, using ethyl 3-(4-{3-[1-(3-cyanophenyl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ 8,18 (s, 1H), 7,86 (s, 1H), 7,74 (s, 1H), 7,71 (d, 1H), 7,55 (t, 1H), to 7.09 (d, 2H), 7,06 (d, 2H), 3,92 (who, 1H), 3.15 in (m, 1H), 3.04 from (m, 1H), 2,74 (t, 2H), 2,48 (t, 2H), 2,02 (m, 1H), was 1.94 (m, 1H), 1,75 (m, 1H), 1,62 (m, 1H), of 1.52 (m, 1H), USD 1.43 (m, 1H), of 1.30 (d, 3H).

Example 291:hydroformed 3-(4-{(1S,3S)-3-[(R)-1-(3-pyrrolidin-1-ylphenyl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1329)

Followed General procedure J, using ethyl 3-(4-{3-[1-(3-pyrrolidin-1-ylphenyl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ compared to 8.26 (2, 1H), 7,07 (m, 4H), 6,60 (d, 1H), 6,55 (s, 1H), 6,40 (d, 1H), of 3.77 (s, 1H), 3,21 (m, 4H), 3.15 in (m, 1H), 3,11 (m, 1H), 2,74 (t, 2H), 2,47 (t, 2H), 2,01 (m, 1H), 1,94 (m, 5H), to 1.79 (m, 1H), 1,64 (m, 1H), 1,53 (m, 1H), USD 1.43 (m, 1H), 1,29 (d, 3H).

Example 292:hydroformed 3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzofuran-5-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1330)

Followed General procedure J, using ethyl 3-(4-{3-[1-(2,3-dihydrobenzofuran-5-yl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ 8,23 (s, 1H), 7,24 (s, 1H), was 7.08 (m, 5H), 6,69 (m, 1H), 4,49 (m, 2H), 3,79 (m, 1H), and 3.16 (m, 3H), to 3.09 (m, 1H), 2,75 (t, 2H), 2,47 (t, 2H), 2,00 (m, 1H), 1,95 (m, 1H), 1.77 in (m, 1H), to 1.63 (m, 1H), of 1.52 (m, 1H), 1,44 (m, 1H), 1.27mm (d, 3H).

Example 293:3-(4-{(1S,3S)-3-[(R)-1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1331)

Followed General procedure J, using ethyl 3-(4-{3-[1-(2,3-dihydrobenzo[1,4]dioxin-6-yl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ 7,1 (m, 5H), of 6.99 (d, 1H), 6.87 in (d, 1H), 4,24 (m, 4H), 4.09 to (m, 1H), 3,26 (m, 2H), was 2.76 (t, 2H), 2,48 (t, 2H), 2,04 (m, 3H), of 1.78 (m, 2H), 1,47 (m, 4H).

Example 294:3-(4-{(1S,3S)-3-[(R)-1-(4-fluoro-3-methoxy-1-ylphenyl)ethylamino]cyclopentyl}phenyl)propionic acid (compound 1332)

Followed General procedure J, using ethyl 3-(4-{3-[1-(4-fluoro-3-methoxy-1-ylphenyl)ethylamino]cyclopentyl}phenyl)propionate.1H NMR (300 MHz, DMSO) δ 7,33 (d, 1H), 7,17 (DD, 1H), was 7.08 (DD, 4H), of 6.99 (m, 1H), 3,99 (m, 1H), 3,84 (s, 3H), 3,19 (m, 2H), 2,75 (t, 2H), 2,18 (t, 2H), 2,01 (m, 2H), 1,89 (m, 1H), 1,68 (m, 1H), 1,62 (m, 1H), the 1.44 (m, 1H), 1,38 (d, 3H).

Example 295:hydrochloride 3-{4-[(1S,3S)-3-((R)-1-benzo[b]thiophene-3-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1333)

Followed General procedure J, using ethyl 3-{4-[3-(1-benzo[b]thiophene-3-ylethylamine)cyclopentyl]phenyl}propionate.1H NMR (300 MHz, DMSO) δ 8,29 (s, 1H), 8,12 (d, 1H), 8,07 (d, 1H), 7,47 (DDD, 2H), 7,10 (DD, 4H), 4,94 (K, 1H), 3,52 (m, 1H), and 3.31 (m, 1H), 2,19 (t, 2H), 2,47 (t, 2H), 2,24 (m, 1H), 2.05 is (m, 2H), 1,96 (m, 1H), to 1.87 (m, 1H), 1,73 (d, 3H), 1,47 (m, 1H).

Example 296:3-{4-[(1S,3S)-3-((R)-1-phenylethylamine)cyclopentyl]phenyl}propionic acid (compound 1334)

Followed General procedure J, using ethyl 3-{4-[3-(1-phenylethylamine)cyclopentyl]phenyl}propionate.1H NMR (300 MHz, DMSO) δ 7,94 (d, 2H), 7,37 (t, 2H), 7,29 (m, 1H), to 7.09 (DD, 4H), 3,99 (m, 1H), 3,17 (m, 2H), 2,75 (t, 2H), 2,47 (t, 2H), 2,02 (m, 2H), of 1.84 (m, 1H), 1.69 in (m, 1H), 1,60 (m, 1H), 1,44 (m, 1H), 1,37 (W.is, 3H).

Preparation 12:ethyl ester of 4-(3S-oxocyclopent)benzoic acid

Followed the General procedure Of using 4-ethoxycarbonylphenyl acid and [Rh(S-BINAP)(nbd)]BF4.1H NMR (300 MHz, CDCI3) δ 8,05-7,98 (m, 2H), was 7.36-7,29 (m, 2H), to 4.38 (K, 2H), 3,55 is 3.40 (m, 1H), of 2,75 2,63 (m, 1H), 2,55-to 2.41 (m, 2H), 2,41 was 2.25 (m, 2H), 2,08-of 1.92 (m, 1H), 1.39 in (t, 3H).

Example 297:ethyl ester 4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1335/1336)

Followed General procedure, But using the ethyl ester of 4-(3S-oxocyclopent)benzoic acid (preparation 12) and (+)-(R)-1-naphthalene-1-ylethylamine. Received two diastereoisomer was shared by preparative chiral HPLC on a column Chiralpak AD-H 250×20 mm, 5 µm at 25°C, UV detection at 280 nm. Isocratic separation with a mixture of n-heptane:ethanol NEt3:CH3COOH(75:15:0,1:0,1); consumption = 17,0 ml/min 1335 Connection: RT = 8,82.1H NMR (300 MHz, DMSO) δ 8,29 (d, 1H), 7.95 is-7,89 (m, 1H), 7,86 (d, 2H), 7,82-of 7.70 (m, 2H), 7,55-7,44 (m, 3H), 7,39 (d, 2H)and 4.65 (K, 1H), 4,29 (K, 2H), 3,11-is 2.88 (m, 2H), 2,41-of 2.27 (m, 1H), 2.26 and with 2.14 (m, 1H), 1,98-of 1.42 (m, 5H), to 1.37 (d, 3H), of 1.31 (t, 3H). Connection 1336: RT = 12,04.1H NMR (300 MHz, DMSO) δ 8.30 to (d, 1H), 7.95 is-7,88 (m, 1H), 7,85-of 7.69 (m, 4H), 7,56 was 7.45 (m, 3H), 7,28 (d, 2H), with 4.64 (K, 1H), 4,27 (t, 2H), 3,35 is 3.23 (m, 1H), 3,21-3,11 (m, 1H), 2,33-of 2.20 (m, 1H), 2,17-2,02 (m, 1H), 1,98-to 1.79 (m, 2H), 1,71-of 1.41 (m, 3H), of 1.38 (d, 3H), of 1.29 (t, 3H).

Example 298:4-[3-((R)-1-naphthalene-1-ylethylamine)qi is lipantil]benzoic acid (compound 1337)

Followed General procedure J, using ethyl ester 4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1335).1H NMR (500 MHz, DMSO) δ 8.30 to (d, 1H), 8,24 (s, 1H), 7,94 (d, 1H), 7,82 (t, 3H), 7,76 (d, 1H), 7,52 (dt, 3H), 7,28 (d, 2H), 4,80 (K, 1H), 3,37 of 3.28 (m, 1H), 3.25 to 3,19 (m, 1H), 2,16-of 2.09 (m, 1H), 2,08-of 1.95 (m, 2H), 1,66 is 1.58 (m, 1H), 1.56 to of 1.41 (m, 5H).

Example 299:4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1338)

Followed General procedure J, using ethyl ester 4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1336).1H NMR (500 MHz, DMSO) δ 8,31 (d, 1H), 8,23 (s, 1H), 7,94 (d, 1H), 7,85-7,79 (m, 3H), to 7.77 (d, 1H), 7,58 is 7.50 (m, 3H), 7,26 (d, 2H), 4,81 (K, 1H), 3,35 is 3.23 (m, 2H), 2,13-2,05 (m, 1H), 1,97-1,89 (m, 2H), 1,76-1,63 (m, 2H), 1,52-of 1.42 (m, 4H).

Example 300:methyl ester 3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoylamine}propionic acid (compound 1339)

To a solution of 4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1338) (100 mg) in DMF (1 ml) was added CDI (53 mg) and DIPEA (33 mg). After stirring the solution at K.T. over 4.5 h was added the hydrochloride of the methyl complex ester of β-alanine (105 mg). The mixture was stirred over night, filtered and purified preparative HPLC-MS (re-analyzed by LC/MS method A).1H NMR (300 MHz, MSO) to 8.41 δ (t, 1H), 8.30 to (d, 1H), 7.95 is-7,87 (m, 1H), 7,81-to 7.64 (m, 4H), EUR 7.57 was 7.45 (m, 3H), 7,21 (d, 2H)and 4.65 (K, 1H)and 3.59 (s, 3H), of 3.46 (DD, 2H), 3,32-3,11 (m, 2H), 2.57 m (t, 2H), 2,28 (sh, 1H), 2,15 for 2.01 (m, 1H), 1,98-1,77 (m, 2H), 1.70 to of 1.41 (m, 3H), of 1.38 (d, 3H).

Example 301:hydrochloride of 1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoyl}piperidine-4-carboxylic acid (compound 1340)

A solution of 4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1338) (104 mg, 0.29 mmol), CDI (56 mg, 0.35 mmol) and DIPEA (50 μl, 0.29 mmol) in dry DMF (2 ml) was stirred at K.T. during the night. Was added ethyl ester piperidine-4-carboxylic acid (168 mg, 0.87 mmol) and the resulting suspension was stirred at K.T. within 3 days. The reaction mixture was filtered, re-suspended in DMSO and was purified preparative HPLC.

The intermediate ethyl ester hydrolyzed to the specified in the title compound following the General procedureJ.13C NMR (151 MHz, DMSO) δ 175,38, 168,84, 145,41, 133,95, 133,83, 133,33, 130,15, 128,90, 128,86, 126,96, 126,83, 126,78, 126,10, 125,54, 124,70, 122,35, 55,41, 50,32, 46,38, 42,61, 39,99, 36,66, 32,97, 29,96, 28,14, 20,50.

Example 302:hydrochloride 3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoylamine}propionic acid (compound 1341)

Followed General procedure J, using methyl ester 3-{4-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]benzoylamine}propionic acid (compound 1339).1H the Mr (600 MHz, DMSO) δ 10,08 (sh, 2H), 8,48 (t, 1H), with 8.33 (d, 1H), with 8.05 (d, 1H), 8,01 (d, 1H), of 7.96 (d, 1H), 7,74 (d, 2H), 7,60 (dt, 3H), 7,25 (d, 2H), 5,28-by 5.18 (m, 1H), 3,50-to 3.35 (m, 4H), 2,53-2,48 (m, 2H), 2,28-2,19 (m, 1H), 2,11-2,04 (m, 1H), 2.00 in to 1.86 (m, 3H), 1.69 in (d, 3H), 1,52 was 1.43 (m, 1H).

Preparation 13:methyl ester of 4-((1S,4S)-4-acetoxysilane-2-enyloxy)benzoic acid

Methyl ester of 4-hydroxybenzoic acid (6 mmol), (1R,4S)-CIS-4-acetoxy-2-cyclopenten-1-ol (4 mmol) and triphenylphosphine (4.8 mmol) were placed in a flask in an argon atmosphere. Dry THF (15 ml) was added through a diaphragm valve, and the resulting solution was cooled to 0°C. DIAD was added dropwise, undiluted, within 20 minutes the Reaction mixture was left overnight. THF was removed in vacuo, and the residue was taken in MTBE, 10 ml, and diluted to double volume PE. After settling for 2 hours in the cold precipitate triphenylphosphine was removed on the filter. The filtrate was concentrated in vacuo and purified by chromatography with a gradient from 0 to 20% EtOAc in heptane.

Preparation 14:methyl ester of 4-((1S,4S)-4-hydroxycyclopent-2-enyloxy)benzoic acid

Methyl ester of 4-(4-acetoxysilane-2-enyloxy)benzoic acid (preparation 13) (3 mmol) and potassium carbonate (3 mmol) were placed in a flask in an argon atmosphere. Was added dry methanol (15 ml) and the resulting suspension was heated at tempera is ur boil with the return of phlegmy within 1 hour when TLC showed complete conversion of substances. The reaction mixture was concentrated in vacuo and purified by chromatography with a gradient from 0 to 90% EtOAc in heptane.13C NMR (75 MHz, CDCl3) δ 166,86, 161,87, 139,76, 133,01, 131,68, 122,64, 114,79, 81,73, 76,01, 51,88, 41,04.

Preparation 15:methyl ester of 4-((1S,4R)-4-harcelement-2-enyloxy)benzoic acid

Methyl ester of 4-(4-hydroxycyclopent-2-enyloxy)benzoic acid (preparation 14) (2 mmol), Teilhard (2.5 mmol) and DMAP (200 µmol) were placed in a vessel. DCM (1 ml) was added through a diaphragm valve followed by the addition of triethylamine (250 Microm). The reaction mixture was left at K.T. at night. The reaction mixture was concentrated in vacuo and purified by chromatography with a gradient from 0 to 60% EtOAc in heptane.13C NMR (75 MHz, CDCl3) δ 166,75, 161,50, 137,52, 132,48, 131,70, 122,95, 114,87, 80,52, 59,82, 51,89, 41,61.

Preparation 16:methyl ester 4-[(1S,4S)-4-((R)-1-naphthalene-1-ylethylamine)cyclopent-2-enyloxy]benzoic acid

Methyl ester of 4-(4-harcelement-2-enyloxy)benzoic acid (preparation 15) (630 mmol), (+)-(R)-1-naphthalene-1-ylethylamine (630 mmol) and potassium carbonate (630 μmol) was placed in a vessel. Was added dry DMF (1 ml) and the resulting suspension was heated at 50°C for 72 hours. The reaction mixture was diluted in the water (25 ml) and was extracted twice with ethyl acetate. The extract was dried, concentrated in vacuo and purified by chromatography with a gradient from 0 to 40% EtOAc in heptane.13C NMR (75 MHz, CDCl3) δ 166,82, 161,93, 140,94, 134,00, 131,64, 131,57, 131,24, 130,32, 129,03, 127,38, 125,86, 125,67, 125,37, 123,23, 122,79, 122,35, 114,76, 81,98, 61,10, 52,01, 51,79, 39,23, 24,10.

Example 303:methyl ester 4-[(1R,3R)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid (compound 1342)

Methyl ester of 4-[4-(1-naphthalene-1-ylethylamine)cyclopent-2-enyloxy]benzoic acid (preparation 16) was diluted to 0.05 M in isopropanol. This solution was passed through the apparatus for hydrogenation H-Cube at a hydrogen pressure of 1 ATM. and the flow rate 1 ml/min over 10% Pd on carbon. The product was concentrated and purified by chromatography with a gradient from 0 to 40% EtOAc in heptane.13C NMR (75 MHz, CDCl3) δ 166,91, 161,78, 141,58, 133,99, 131,57, 131,50, 131,23, 129,00, 127,22, 125,81, 125,63, 125,35, 122,85, 122,79, 122,15, 114,92, 78,33, 56,02, 52,09, 51,78, 40,71, 31,86, 31,06, 24,03.

Example 304:formate 4-[(1R,3R)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid (compound 1343)

Followed General procedure J, using methyl ester 4-[3-(1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid (compound 1342).13C NMR (75 MHz, DMSO) δ 167,01, 163,75, 160,88, 140,56, 133,38, 131,14, 130,68, 128,63, 126,96, 125,87, 125,52, 125,34, 123,19, 122,97, 122,81, 114,79, 77,87, 55,23, 51,22, 38,71, 30,41, 30,36, 23,33.

Preparation 17:ethyl ester of 3-((1S,4S)-4-acetoxysilane-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid

Ethyl ester 5-methyl-1H-imidazole-4-carboxylic acid (6 mmol), (1R,4S)-CIS-4-acetoxy-2-cyclopenten-1-ol (4 mmol) and triphenylphosphine (4.8 mmol) were placed in a flask in an argon atmosphere. Dry THF (15 ml) was added through a diaphragm valve and the resulting solution was cooled to 0°C. DIAD was added dropwise, undiluted, within 20 minutes the Reaction mixture was left overnight, the THF was removed in vacuum and the residue was taken in MTBE, 10 ml, and diluted to double volume PE. After settling for 2 hours in the cold precipitate triphenylphosphine was removed on the filter. The filtrate was concentrated in vacuo and purified by chromatography with a gradient from 0 to 20% EtOAc in heptane.1H NMR (300 MHz, CDCl3) δ the 7.43 (s, 1H), 6,28 (m, 1H), 6,17 (m, 2H), of 5.83 (m, 1H), 4,34 (K, 2H), 2,58 (DDD, 1H), 2.49 USD (s, 3H), of 2.16 (DDD, 1H), 2.05 is (s, 3H), of 1.39 (t, 3H).

Preparation 18:ethyl ester of 3-((1S,4S)-4-hydroxycyclopent-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid

Ethyl ester of 3-(4-acetoxysilane-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid (preparation 17) (3 mmol) and potassium carbonate (3 mmol) were placed in a flask in an argon atmosphere. Dry methanol (15 ml) was added and the resulting suspension was heated at is the temperature of boiling with the return of phlegmy within 1 hour when TLC showed complete conversion of substances. The reaction mixture was concentrated in vacuo and purified by chromatography with a gradient from 0 to 90% EtOAc in heptane.1H NMR (300 MHz, CDCl3) δ 7,41 (s, 1H), 6,28 (m, 1H), 6,12 (m, 1H), 6,04 (m, 1H), 5,08 (m, 1H), 4,34 (K, 2H), 3,62 (sh, 1H), 2,47 (s, 3H), 2,42 (m, 1H)m, and 2.14 (m, 1H), 1.39 in (t, 3H).

Preparation 19:ethyl ester of 3-((1S,4R)-4-harcelement-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid

Ethyl ester of 3-(4-acetoxysilane-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid (preparation 18) (2 mmol), Teilhard (2.5 mmol) and DMAP (200 µmol) were placed in a vessel. DCM (1 ml) was added through a diaphragm valve followed by the addition of triethylamine (250 Microm). The reaction mixture was left at K.T. at night. The reaction mixture was concentrated in vacuo and purified by chromatography with a gradient from 0 to 60% EtOAc in heptane.1H NMR (300 MHz, CDCl3) δ to 7.61 (s, 1H), 6,29 (m, 1H), 6,09 (m, 1H), 6,01 (m, 1H), 4.95 points (m, 1H), 4,34 (K, 2H), 3,20 (m, 1H), 2,48 (s, 3H), of 2.15 (m, 1H), 1,38 (t, 3H).

Preparation of 20:ethyl ester 5-methyl-3-[(1S,4S)-4-((R)-1-naphthalene-1-ylethylamine)cyclopent-2-enyl]-3H-imidazole-4-carboxylic acid

Ethyl ester of 3-(4-harcelement-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid (preparation 19) (630 mmol), (+)-(R)-1-naphthalene-1-ylethylamine (630 mmol) and potassium carbonate (630 is KMOL) was placed in a vessel. Dry DMF (1 ml) was added and the resulting suspension was heated at 50°C for 72 hours. The reaction mixture was diluted with water (25 ml) and was extracted twice with ethyl acetate. The extract was dried, concentrated in vacuo and purified by chromatography with a gradient from 0 to 40% EtOAc in heptane.1H NMR (300 MHz, CDCl3) δ 8,19 (d, 1H), a 7.85 (d, 1H), 7,71 (m, 2H), 7,47 (m, 3H), 7,30 (s, 1H), 6,16 (m, 1H), 6,04 (m, 1H), 5,88 (m, 1H), 4,74 (K, 1H), 4,33 (K, 2H), 3,94 (m, 1H), of 2.45 (s, 3H), 2,35 (m, 1H), 2.05 is (m, 1H), to 1.48 (d, 3H), of 1.38 (t, 3H).

Example 305:5-methyl-3-[(1R,3R)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]-3H-imidazole-4-carboxylic acid (compound 1344)

Stage 1:

Ethyl ester 5-methyl-3-[4-(1-naphthalene-1-ylethylamine)cyclopent-2-enyl]-3H-imidazole-4-carboxylic acid (preparation 20) was diluted to 0.05 M in isopropanol. This solution was passed through the apparatus for hydrogenation H-Cube at a hydrogen pressure of 1 ATM. and the flow rate 1 ml/min over 10% Pd on carbon. The product was concentrated and purified by chromatography with a gradient from 0 to 40% EtOAc in heptane, getting ethyl ester 5-methyl-3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]-3H-imidazole-4-carboxylic acid.

Stage 2:

Followed General procedure J, using ethyl ester 5-methyl-3-[3-(1-naphthalene-1-ylethylamine)cyclopentyl]-3H-imidazole-4-carboxylic acid.1H NMR (300 MHz, DMSO) δ of 8.27 (m, 1H), 7,95 (m, 1H), 7,86 (m, 1H), 7,78 (m, 1H), 7,71 (m, 1H), rate of 7.54 (m, 3H), 5,43 (m, 1H), 4,87 (m, 1H), 3,37 (m, 1H), 2,31 (s, 3H), of 2.20 (m, 2H), 2.05 is-of 1.55 (m, 4H), for 1.49 (d, 3H).

Example 306:(3S,4S-diphenylthiophene)-((R)-1-naphthalene-1-retil)amine (compound 1345)

Followed General procedure A, using the 3S,4S-diphenylcyclopropane and (+)-(R)-1-naphthalene-1-ylethylamine.1H NMR (300 MHz, CDCl3) δ 8,19 (d, 1H), to $ 7.91-to 7.84 (m, 1H), 7,76 (d, 1H), 7,72-to 7.64 (m, 1H), 7,55-7,42 (m, 3H), 7.23 percent-6,97 (m, 10H), 4,84-to 4.73 (m, 1H), 3,48 of 3.28 (m, 2H), 3,05 of 2.92 (m, 1H), 2,52-of 2.38 (m, 1H), 2,17-2,00 (m, 2H), 1,89-1,70 (m, 1H), and 1.54 (d, 3H).

Example 307:5-(4-ethoxyphenyl)-2-propylcyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1346)

A solution of 3-(4-ethoxyphenyl)6-propylcyclohexyl-2-Aenon (100 mg) in isopropanol (8 ml) was hydrogenosomal in the H-CUBE (catalyst: Pd/C, flow rate: 1 ml/min, pressure H2: 1 bar, and the outline size: 5 ml). Conjugated double bond was hydrogenosomal 2 run (~80% conversion). Evaporation of the isopropanol was the result of a colorless oil, which was dissolved in acetonitrile (3 ml). (R)-1-naphthalene-1-ylethylamine and NaBH(OAc)3was added and the reaction mixture was stirred over night at room temperature. The reaction mixture was extracted with EtOAc/NaHCO3aq. The organic phase was dried (MgSO4) and evaporated after filtration. The oil was dissolved in methanol and was purified preparative HPLC-MS. LC/MS (method B): RT = 3.72 points, [M+H]+= 416,6.

Example 308:

A mixture of [2-(4-forfinal)-5-oxocyclopent-1-enyl]acetic acid and 10% Pd/C in methanol was left in an atmosphere of H2for 3 days. The reaction mixture was filtered through celite and evaporated to an oil. The oil was dissolved in acetonitrile. (R)-1-naphthalene-1-ylethylamine and NaBH(OAc)3was added and the reaction mixture was stirred over night at room temperature. The reaction mixture was extracted with EtOAc/NaHCO3aq. The organic phase was isolated, dried (MgSO4) and evaporated after filtration. The oil was dissolved in methanol and was purified preparative HPLC-MS, receiving the desired product. The desired product was dissolved in acetonitrile. Was added HCl in dioxane (1 EQ.), and has precipitated salt with HCl product (specified in the header of the connection), and the product was collected by filtration.1H NMR (300 MHz, DMSO) δ 12,37 (sh, 1H), 9,71 (sh, 2H), 8,28 (d, 1H), 8,09-of 7.96 (m, 3H), 7,69-7,56 (m, 3H), 7,38-7,28 (m, 2H), 7,12 (t, 2H), 5,43-of 5.29 (m, 1H), a 3.87-to 3.73 (m, 1H), 2,86-a 2.71 (m, 1H), 2,58 at 2.45 (m, 1H), 2,44-of 2.36 (m, 2H), 2,14 of-1.83 (m, 4H), of 1.75 (d, 3H).

Example 309:3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propan-1-ol (compound 1348)

To a solution of ester methyl 3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1183) (215 mg, 0.54 mmol) in dry diethyl simple ether (3 ml) was added LiAlH4(of 0.62 ml of 1 M solution in THF) PR is 0°C. After 30 min the reaction mixture was extinguished with water and was purified preparative HPLC, getting mentioned in the title compound in the form of butter.1H NMR (300 MHz, DMSO) δ 8.30 to (d, 1H), 7.95 is-7,87 (m, 1H), 7,80-to 7.68 (m, 2H), EUR 7.57-7,44 (m, 3H), 7,03 (s, 4H), with 4.64 (K, 1H), 4,42 (t, 1H), 3.46 in-3,29 (m, 2H), 3,24-is 3.08 (m, 2H), 2,59-2,47 (m, 2H), 2,35-of 1.30 (m, 11H).

Example 310:Functional analysis of whole cells

On the day of analysis cells were collected and re-suspended until 13.106cells/ml in a stimulating buffer (containing: Hepes l0 mm MgCl20.5 mm, KCl 4.2 mm, 146 mm NaCl, 5.5 mm glucose, LiCl 50 mm, pH 7,4). Five μl of the cell solution was transferred by pipette into the hole (white 384-well plate, Perkin Elmer Optiplate), followed by adding 5 μl of compound diluted in containing Ca2+the buffer (to a final concentration of 2 mm). After stimulation with compound for 1 hour at 37°C was added 10 μl of reagents for the analysis of IP-One and carried out the incubation in the next 1 hour at room temperature. And finally, the tablet was read using a Perkin Elmer EnVision, according to the Protocol supplied by the manufacturer of the test kit IP-One. The ratio of FRET was calculated by dividing the emission signal at 665 nm signal at 615 nm.

The molar concentration of the compound that gave 50% of the maximum agonist response (IC50 value), calculated according to the equation total sigmoid is Riva and with the slope of the hill from a to d (equation 1). This model describes a sigmoidal curve with a matched reference line, a. The equation can be applied to align the curves, where the response is either increasing, or decreasing, taking into account the independent variable, X.

Equation 1. y = (a - d)/(1 + (x/c)Λb) + d

Parameters:

x = concentration of the test compounds

y = response (%)

a = minimum response when the concentration approaches 0

d = the maximum response when the concentration of the test compounds increasing

c = IC50 curve

b = hill coefficient or the slope of the curve

These tests of the compounds of this invention show that the compounds according to this invention are strong CaSR modulators, which makes them potentially applicable for the treatment of diseases related to the kidneys or bones. See table 1 below.

Table 1
In vitrotest compounds in CaSR functional analysis of whole cells
connectionIC50 (nm)
Cinacalcet (cinacalcet)630
connection 1056250
connection 1115 50
connection 113640
connection 114250
connection 114650
connection 118640
connection 118820
connection 11908
connection 133816

Example 311:Screening for inhibition of P450 2D6

The analysis provides rapid screening of potential inhibitors of the catalytic activity of P450 2D6 person when using recombinant P450 2D6 person. Determination of IC50 performed twice at eight concentrations.

Incubation was performed in 96-well titration microplate-based method described by BD Biosciences. In the first well of each row was added regenerating system NADPH and tested the connection. The second hole, and all remaining wells were added to the recycling system of NADPH and acetonitrile (final concentration 2%). Final analytical concentration of the regenerating system NADPH was of 8.2 μm NADP+, 0,41 mm glucose-6-phosphate, 0,41 mm uranyl magnesium chloride and 0.4 units/ml glucose dehydrogenase-6-fo the veil and 0.01 mg/ml of the control of cell membrane protein insects. The solution of the test compounds serially diluted 1:3 in eight holes. The final concentration of the tested compounds was in the range of from 100 μm-45.7 nm in eight rows. Wells 9 and 10 did not contain the test compounds (only regenerating system NADPH and the mixture of the enzyme/substrate) and the wells 11 and 12 were used as controls for background fluorescence (enzyme and substrate was added after termination of the reaction). The tablet is then subjected to pre-incubation at 37°C for 10 min and the reaction was initiated by addition of pre-heated mixture of the enzyme/substrate. Analytical concentration of the mixture of the enzyme/substrate was 100 mm potassium phosphate, pH of 7.4, 1.5 pmol of recombinant P450 CYP2D6 man and 1.5 μm fluorescent substrate 3-[2-(N,N diethyl-N-methylamino)ethyl]-7-methoxy-4-methylcoumarin (AMMC). The analysis was performed in duplicate in a final volume of 200 µl per well. Reactions were stopped after 30 min by addition of a mixture of 4:1 acetonitrile:0.5 M solution of Tris base. Quinidine was used as a positive control, 0.5 µm as the highest concentration. Fluorescence per well was measured using an apparatus for reading fluorescence tablet (excitation: 390 nm, emission: 460 nm). The IC50 value was calculated.

These tests of the compounds of this invention show that the compounds according to this invention detects the weak inhibition or no inhibition against P450 2D6 (pIC50 value below 6). See table 2 below.

Table 2
In vitrothe test compounds in the analysis of inhibition of CYP 2D6 and CYP 3A4
ConnectionIC50 (μm)
Cinacalcet (Cinacalcet)0,050
Connection 118650
Connection 119079
Connection 1338100
Connection 114616
Connection 114225
Connection 113610
Connection 111513
Connection 105610

Example 312:Profiling of compounds according to this invention on non-coupled receptors G-protein

The connection according to this invention along with Cinacalcet sent to CEREP for functional tests on cell membrane receptors. All experiments were performed on the receptors of the man who expressed to glue the hands of a mammal. ECSO(agonism) and IC50(antagonism) was calculated on a 6-point curve with concentrations between 0.01-100 mm.

The results of functional screening on a cellular basis showed that the compound of this invention was significantly less severe on the opiate receptor (MOR), the serotonin receptor 5-HT1A and Transporter uptake of norepinephrine compared to Cinacalcet.

Example 313:Profiling of compounds according to this invention in relation to the heart of ion channels in vitro

The compounds of this invention were tested in vitro on three cardiac ion channels, which are responsible for the three major components of potential cardiac activity. These channels are:

1. Cloned hERG potassium channels (encoded gene KCNH2 and expressed in embryonic kidney human HEK293 cells), responsible for the IKg

2. Cloned hNavl.5 sodium channel (encoded gene SCN5A person and expressed in HEK293 cells), responsible INafast current sodium

3. Cloned calcium channels, L-type (hCavl.2 encoded gene CACNA1C person in CHO cells), responsible for the ICa,L; high threshold calcium current.

The effect of the compounds of this invention were evaluated in ChanTest Corporation, Ion Channel Company, Cleveland, Ohio, USA. The compound was tested at room temperature, is using the PatchXpress 7000A (Molecular Devices) on the channels, listed above, and were evaluated at 0,01, 0,1, 1, 10 and 100 μm, with each concentration tested in 2-6 cells (n ≥ 2) within 5 min. the Effect of compounds on hNavl.5 was determined by applying a repetitive stimulation of 5 Hz for 5 minutes

The value of the IC50for the test compounds were >100 μm in the analysis of hERG channels and hCavl.2. No-dependent application of inhibition was not observed when konzentrierte up to 100 μm channel hNav1.5. The results of positive controls (E-4031 for hERG, lidocaine for hNav1.5 and nifedipine for hCav1.2) confirmed the sensitivity of the test system. In General, found no significant effects on three of the cardiac ion channel that is responsible for the three major components of potential cardiac activity.

Example 314:In vivo test in normal rats

Various compounds were injected with normal male rats Sprague Dawley, in order to investigate the pharmacological effects on the levels of serum total calcium and hormone parathyroid (PTH). The experiments were performed by oral administration of a single dose of the corresponding compounds when compared with animals that were injected carrier, or the animals that received competitive connection Cinacalcet.

As standard, the group of six animals were given orally 1 mg/kg compound in the form of su whom pensii in 1% methylcellulose and two hours later the blood was collected retrogression exsanguination under anesthesia, and measured the levels of serum calcium and PTH. The percentage suppression of PTH and calcium, respectively, in comparison with animals treated with the carrier, shown in table 3.

In some cases, rats were administered orally with different doses of this compound in 1% methylcellulose (six rats/dose), and blood was collected retrogression exsanguination after two hours. The curves of changes in response to the dose to suppress the levels of serum PTH and serum calcium these compounds are given in figures 1-4. Using the software GraphPad Prism® 5, expected value ED50for Cinacalcet, connections, 1056, 1186 connection and connection 1190, with regard to suppression of PTH, they were 0.9 mg/kg, 0.1 mg/kg, 0.04 mg/kg and 0.002 mg/kg, respectively.

When testing some compounds to rats did bloodletting at different time points after oral administration (six rats/time point), and suppressed levels of serum PTH was observed over time. The results are shown in figures 5-8.

Table 3
The percentage suppression of PTH and calcium, respectively, the compounds according to this invention in comparison with the animals treated with the media.
Connection Dose p.o.Suppression of PTHSuppression of Ca2+

Cinacalcet1 mg/kg48%5%
Connection 10561 mg/kg85%1%
Connection 11151 mg/kg50%3%
Connection 11361 mg/kg61%7%
Connection 11461 mg/kg84%0%
Connection 11861 mg/kg98%6%
Connection 11881 mg/kg97%12%
Connection 11901 mg/kg93%18,5%
Connection 1338 1 mg/kg85%29%

Example 315:In vivo test using the model of 5/6 nephrectomy in rats.

Lowering the effects of various compounds on serum PTH was investigated in vivo in a rat model of 5/6 nephrectomy, which is an accepted animal model of hyperparathyroidism.

Two-thirds of the left kidney of rats (Sprague Dawley, age at least 8 weeks) were surgically removed, followed by removal of the right kidney in a week. Immediately after this procedure, the rodent diet was changed from the standard diet (Altromin, 0.9% of Ca2+, 0.7% of Pi) to diets with a high content of phosphorus (Altromin, 0.9% of Ca2+, 1.2% of Pi), and animals were monitored for 3 weeks, during which they developed severe secondary hyperparathyroidism.

After iniciirovanie diseases of the blood was collected retrogression by phlebotomy and urine were collected using metabolic cages. Serum PTH, calcium, phosphorus, albumin, creatinine and BUN, and creatinine and albumin in the urine was measured. Rats were then divided into different treatment groups (9-12 rats/group) on the basis of the obtained results. One group of normal rats without surgery served as controls ("control"), and one group of rats underwent nephrectomy treated with vehicle (1% methylcellulose)was used as another control ("5/6 NEPX"). All other group is s were treated orally with the test compound at various doses once a day for two weeks, and these parameters were monitored on a weekly basis.

As shown in figure 9, the effect of lowering PTH test compounds was confirmed. The calculated values of the ED50for Cinacalcet, connections, 1056, 1186 connection and connection 1190 were approximately 20 mg/kg, 2 mg/kg, 0.3 mg/kg and 0.01 mg/kg, respectively.

1. The compound of General formula I

where
the groupis cycloalkyl containing 4-7 carbon atoms, optionally substituted by one or more, same or different substituents selected from R2, R3, R4or R5;
A represents 1-naphthyl;
R1represents methyl, ethyl or n-propyl,
each of which is optionally substituted by one or more, same or different substituents selected from halogen and hydroxy;
R2and R3represent hydrogen;
R4represents hydrogen, halogen, hydroxy or C1-6alkyl;
each R5is independently one or more identical or different substituents represented by hydrogen or C1-6by alkyl;
G represents-C(O)NH2With3-8cycloalkyl, C1-6heteroseksualci, C1-6geteroseksualen,3-8cycloalkenyl,6-14aryl, C1-10heteroaryl,
With6-10arylamino, hydroxyaminoindan is l, With6-10allumination,
C1-4aminocarbonyl, C1-6geterotsiklicheskikh,
C1-10heteroarylboronic,
With6-10arylsulfonamides,6-14aryloxy, or
C1-4alkoxycarbonyl,
where specified-C(O)NH2With3-8cycloalkyl, C1-6heteroseksualci, C1-6geteroseksualen,3-8cycloalkenyl,6-14aryl, C1-10heteroaryl,6-10arylamino, hydroxyaminobuteroyl,6-10allumination, C1-4aminocarbonyl, C1-6geterotsiklicheskikh, C1-10heteroarylboronic,6-10arylsulfonamides,6-14aryloxy, C1-4alkoxycarbonyl
are optionally additionally substituted by one or more identical or different substituents, such as halogen, cyano, carboxy, -NH2mono - or di(C1-6alkyl) amino, aminomethyl, gidroksilaminami, amidino, hydroxy, mercapto, -S(O)H, -C(O)NH2, nitro, oxo, trifluoromethyl, C1-6alkyl, C2-4alkenyl,2-4quinil, C1-4hydroxyalkyl, amino1-3alkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4alkylsulphonyl, C1-4aminocarbonyl, hydroxyaminobuteroyl,3-6cycloalkylcarbonyl, C1-6heterocyclizations,3-63-6cycloalkenyl, C1-6cyclooctylamino, C1-6heteroseksualci, C1-6geteroseksualen, C1-6geterotsiklicheskikh,6-14aryl, carboxy6-10aryl, C1-6heteroaryl, C1-6heteroarylboronic, -S(O)2NH2C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic, C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-6heterocyclizations, C1-4alkylthio, C1-4aminosulfonyl,
C1-4aminocarboxylate, C1-4alkylsulfonamides,6-10arylamino,
With6-10allumination,6-10aryloxyalkyl, C1-4alkoxycarbonyl,
With6-10arylcarboxamide,6-10arylsulfonamides, C1-4alkylcarboxylic, C1-4alkenylamine,3-6cycloalkylcarbonyl,
With3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl,
C1-6geterotsiklicheskikh, C1-4alkylsulfonyl,
C1-6heterocyclisation or
C1-3alkylsulfonamides,
where specified carboxy, mono - or di(C1-6alkyl)amino, aminomethyl, gidroksilaminami, -C(O)NH2C1-6alkyl, C2-4alkenyl,2-4quinil,
C1-4hydroxyalkyl, amino1-3alkyl, C1-6halogenated, C1-4alkoxy,
C1-4aldoxycarb the Nile, C1-4alkylsulphonyl, C1-4aminocarbonyl, hydroxyaminobuteroyl,3-6cycloalkylcarbonyl,
C1-6heterocyclizations,3-6cycloalkyl,
With3-6cycloalkenyl, C1-6cyclooctylamino, C1-6heteroseksualci,
C1-6geteroseksualen, C1-6geterotsiklicheskikh,6-14aryl, carboxy6-10aryl, C1-6heteroaryl, C1-6heteroarylboronic,
-S(O)2NH2C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic,
C1-4alkoxycarbonyl, C1-4alkoxycarbonyl,
C1-6heterocyclizations, C1-4alkylthio, C1-4aminosulfonyl,
C1-4aminocarboxylate, C1-4alkylsulfonamides,6-10arylamino,6-10allumination,6-10aryloxyalkyl, C1-4alkoxycarbonyl,
With6-10arylcarboxamide,6-10arylsulfonamides,
C1-4alkylcarboxylic, C1-4alkenylamine,
With3-6cycloalkylcarbonyl,3-6cycloalkylcarbonyl,
C1-4alkoxycarbonyl, C1-6geterotsiklicheskikh,
C1-4alkylsulfonyl, C1-6heterocyclisation or
C1-3alkylsulfonamides
are optionally additionally substituted by one or more, identical is mi or different substituents, selected from such as hydroxy, -NH2mono - or di-(C1-6alkyl)C1-6amino, aminomethyl, gidroksilaminami, carboxy, trifluoromethyl, halogen, oxo, mercapto, cyano, -C(O)NH2, nitro, C1-6alkyl, C2-4alkenyl,2-4quinil, C1-4hydroxyalkyl,
C1-6halogenated, C1-3alkoxy, C1-4alkoxycarbonyl,
C1-4alkylsulphonyl,3-8cycloalkyl,3-8cycloalkenyl,
C1-6heteroseksualci,6-12aryl, C1-10heteroaryl, C1-3alkoxyl6-10aryl, C1-10heterocollateral, C1-6geteroseksualen, -S(O)2NH2,
-S(O)2OH, -S(O)2CH3C1-6ureido, C1-6toureiro,
C1-4alkylcarboxylic, C1-4alkoxycarbonyl,
C1-4alkoxycarbonyl, C1-4alkoxycarbonyl,
C1-4aminocarbonyl, C1-6geterotsiklicheskikh, C1-4alkylthio,
C1-4aminosulfonyl, C1-4aminocarboxylate,
C1-4alkylsulfonamides,6-14arylsulfonyl,
With6-10arylsulfonamides, gidroksilaminami,
C1-4alkylcarboxylic or C1-4alkylsulfonyl,
where specified-C(O)NH2mono - or di(C1-6alkyl)amino, C1-6alkyl, C2-4alkenyl,
With2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-3alkoxy,
C14 alkoxycarbonyl,3-8cycloalkyl,3-8cycloalkenyl,
C1-6heteroseksualci, C6-12aryl, C1-10heteroaryl, C1-3alkoxyl6-10aryl, C1-10heterocollateral, C1-6geteroseksualen, -S(O)2NH2, S(O)2OH, C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic,
C1-4alkoxycarbonyl, C1-4alkoxycarbonyl,
C1-4alkoxycarbonyl, C1-4aminocarbonyl,
C1-6geterotsiklicheskikh, C1-4alkylthio, C1-4aminosulfonyl, C1-4aminocarboxylate, C1-4alkylsulfonamides,6-14arylsulfonyl,
With6-10arylsulfonamides, gidroksilaminami,
C1-4alkylcarboxylic or C1-4alkylsulfonyl
are optionally additionally substituted by one or more, same or different substituents selected from such as hydroxy, oxo, cyano, halogen, trifluoromethyl,
C1-3alkoxy, C1-3alkoxy, C1-3alkoxy, mono - or di-(C1-6alkyl)amino, mercapto, carboxy, -C(O)NH2, nitro, C1-6alkyl, C1-3hydroxyalkyl, C1-4alkoxycarbonyl, C1-3alkylcarboxylic, C1-6heteroseksualci,6-12aryl, C1-6heteroaryl, -S(O)2NH2, -S(O)2OH;
or G with R4forms oxoprop;
provided that Obedinenie is not so, as
N-(3,5-bis(trifluoromethyl)benzyl)-3-((1-(naphthalen-1-yl)ethyl)amino)cyclopentanecarboxylic,
or its pharmaceutically acceptable salt or in vivo hydrolyzable ester.

2. The compound according to claim 1, where the connection is

3. The compound according to claim 1 or 2, where a group of the formulais

4. The compound according to claim 1 or 2, where G is-C(O)R6where R6represents-NH2mono - or di-(C1-6alkyl)amino, hydroxy, mercapto, C(O)NH2, trifluoromethyl, carboxy, C1-6alkyl, C2-4alkenyl,2-4quinil,
C1-4hydroxyalkyl, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-4aminocarbonyl,3-6cycloalkyl,3-6cycloalkenyl,
C1-6geteroseksualen,3-6cyclooctylamino, C1-6heteroseksualci,
C1-6geterotsiklicheskikh,6-14aryl, C1-6heteroaryl,6-10arylamino, carboxy C6-10aryl, C1-4alkylcarboxylic, C1-4alkoxycarbonyl,
C1-4alkoxycarbonyl, C1-4alkylthio, C1-4aminocarboxylate,
C1-4alkylsulfonyl, C1-4alkylcarboxylic,
C1-4alkenylamine,3-6cycloalkylcarbonyl,
With3-6cycloalkylcarbonyl, C1-4 alkoxycarbonyl,
With6-10arylcarboxamide or6-10arylsulfonamides,
where mentioned mono - or di-(C1-6alkyl)amino, C1-6alkyl, C2-4alkenyl,2-4quinil, C1-4hydroxyalkyl, C1-6halogenated, C1-4alkoxy,
C1-4alkoxycarbonyl, C1-4aminocarbonyl,3-6cycloalkyl,
With3-6cycloalkenyl, C1-6geteroseksualen,3-6cyclooctylamino,
C1-6heteroseksualci, C1-6geterotsiklicheskikh,6-14aryl,
C1-6heteroaryl,6-10arylamino, carboxy6-10aryl,
C1-4alkylcarboxylic,C1-4alkoxycarbonyl,
C1-4alkoxycarbonyl, C1-4alkylthio, C1-4aminocarboxylate,
C1-4alkylsulfonyl, C1-4alkylcarboxylic,
C1-4alkenylamine,3-6cycloalkylcarbonyl,
With3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl,
With6-10arylcarboxamide or6-10arylsulfonamides can be further optionally substituted by one or more identical or different substituents, such as hydroxy, halogen, C1-4alkyl, C1-3alkoxy, C1-4alkoxycarbonyl, C1-6heteroseksualci,6-12aryl or oxo,
where specified C1-4alkyl, C1-3alkoxy, C1-4 alkoxycarbonyl,
C1-6heteroseksualci or6-12aryl are optionally additionally substituted by trifluoromethyl, halogen, C1-4the alkyl, C1-3alkoxy or C1-4alkoxycarbonyl.

5. The compound according to claim 4, where G represents-C(O)NH2C1-4aminocarbonyl, C4-5geterotsiklicheskikh, C6-10allumination, C6-10arylsulfonamides,
where specified C1-4aminocarbonyl, C4-5geterotsiklicheskikh,6-10allumination,6-10arylsulfonamides are optionally substituted by one or more, same or different substituents selected from oxo, hydroxy, C1-4of alkyl,
C1-3alkoxy, C1-3alkoxycarbonyl, C4-5geterotsiklicheskie,6-10aryl,
where specified C1-4alkyl, C1-3alkoxy, C1-3alkoxycarbonyl,4-5heteroseksualci or6-10aryl are optionally substituted by one or more identical or different substituents, such as halogen, trifluoromethyl, C1-3alkoxy or C1-3alkoxycarbonyl.

6. The compound according to claim 5, where G represents methylpiperazine, cyclopropanecarbonyl, isopropylaminocarbonyl, propylaminoethyl, morpholinoethyl, dimethylaminoethyl, isobutylparaben, atilim noncarbonyl, N-methoxy-N-methylaminomethyl, methoxycarbonylaminophenyl, methoxyethylamine, ethoxycarbonylpyrimidine, dimethyldithiocarbamic, morpholinepropanesulfonic, ethoxycarbonylpyrimidine, chlorobenzenesulfonyl, phenylhydroxylamine, ethoxycarbonylmethylene, triftormetilfullerenov, hydroxyindoleacetic, phenylmethanesulfonyl, methoxyacetophenone, triptoreline, methoxycarbonylaminophenyl, methylphenylethylamine or carboxymethylaminomethyl.

7. The compound according to claim 1 or 2, where G represents phenyl, optionally substituted by one or more, same or different substituents selected from such as-C(O)H, -C(O)NH2, hydroxy, halogen, cyano, nitro, amidino, carboxy, trifluoromethyl,
C1-6alkyl, C2-4alkenyl,2-4quinil, C1-4hydroxyalkyl, C1-6amino, amino1-3alkyl, iminomethyl, gidroksilaminami, C1-6halogenated, C1-4alkoxy, C1-4alkoxycarbonyl, C1-3alkoxycarbonyl,
C1-4aminocarbonyl, C1-3alkylsulfonamides, hydroxyaminobuteroyl, C1-6heterocyclizations,
C1-6heterocyclizations,3-6the cycle is alkylaminocarbonyl, With6-10allumination, C1-10heteroarylboronic,3-6cycloalkyl,
C1-6heteroseksualci, C1-6geteroseksualen,
C1-6geterotsiklicheskikh, C1-4alkylcarboxylic,
C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkylthio,3-6cycloalkenyl, C1-4aminosulfonyl, C1-4aminocarboxylate,
C1-4alkylsulfonyl, C1-10heteroaryl,6-10arylamino,
With6-10aryloxyalkyl,6-10arylcarboxamide,
With6-10arylsulfonamides, C1-4alkylcarboxylic,
C1-4alkenylamine,3-6cycloalkylcarbonyl,
With3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl,
C1-6geterotsiklicheskikh, C1-4alkylsulfonyl or
C1-4heterocyclisation,
where these C(O)NH2C1-6alkyl, C2-4alkenyl,2-4quinil,
C1-4hydroxyalkyl, C1-6amino, amino1-3alkyl, iminomethyl, gidroksilaminami, C1-6halogenated, C1-4alkoxy,
C1-4alkoxycarbonyl, C1-3alkoxycarbonyl, C1-4aminocarbonyl,
C1-3alkylsulfonamides, hydroxyaminobuteroyl,
C1-6heterocyclizations, C1-6heterocyclizations,
With3-6cycloalkyl aminocarbonyl, With6-10allumination,
C1-10heteroarylboronic,3-6cycloalkyl,
C1-6heteroseksualci, C1-6geteroseksualen,
C1-6geterotsiklicheskikh, C1-4alkylcarboxylic,
C1-4alkoxycarbonyl, C1-4alkoxycarbonyl, C1-4alkylthio,3-6cycloalkenyl, C1-4aminosulfonyl, C1-4aminocarboxylate,
C1-4alkylsulfonyl, C1-10heteroaryl,6-10arylamino,
With6-10aryloxyalkyl,6-10arylcarboxamide,
With6-10arylsulfonamides, C1-4alkylcarboxylic,
C1-4alkenylamine,3-6cycloalkylcarbonyl,
With3-6cycloalkylcarbonyl, C1-4alkoxycarbonyl,
C1-6geterotsiklicheskikh, C1-4alkylsulfonyl or
C1-4heterocyclisation
are optionally additionally substituted by one or more, same or different substituents selected from the group consisting of such substituents as hydroxy, -NH2,
mono - or di-(C1-6alkyl)amino, aminomethyl, gidroksilaminami, carboxy, trifluoromethyl, halogen, oxo, mercapto, cyano, -C(O)NH2, nitro,
C1-6alkyl, C2-4alkenyl,2-4quinil, C1-4hydroxyalkyl,
C1-6halogenated, C1-3alkoxy, C 1-4alkoxycarbonyl,
C1-6geterotsiklicheskikh,3-6cycloalkyl,3-6cycloalkenyl,
C1-6heteroseksualci, C6-12aryl, C1-10heteroaryl, C1-3alkoxyl6-10aryl, C1-10heterocollateral, C1-6geteroseksualen, -S(O)2NH2, S(O)2OH, C1-6ureido, C1-6toureiro, C1-4alkylcarboxylic,
C1-4alkoxycarbonyl, C1-4alkoxycarbonyl,
C1-4alkoxycarbonyl, C1-4aminocarbonyl, C1-4alkylthio,
C1-4aminosulfonyl, C1-4aminocarboxylate,
C1-4alkylsulfonamides; C6-12arylsulfonyl,
With6-10arylsulfonamides, C1-4alkylcarboxylic or
C1-4alkylsulfonyl,
where specified3-8cycloalkyl, C1-6alkyl, C1-3alkoxy,
C1-4alkoxycarbonyl, C1-6heteroseksualci,6-10aryl or
C1-10heteroaryl can be optionally substituted by carboxy, halogen, hydroxy, cyano, C1-6heterocyclization, one or more C1-6alkilani, C1-3alkoxy, C1-3alkoxyl1-3alkoxy, C1-4alkoxycarbonyl, C1-3hydroxyalkyl or6-10Allami.

8. The connection according to claim 7, where G is phenyl, substituted by one or more identical or different substituents, vibrancies such as cyano, carboxy, -C(O)H, -C(O)NH2, hydroxyl, halogen, amidino, iminomethyl, gidroksilaminami,
C1-6alkyl, C2-4quinil, aminos1-3alkyl, C1-3alkoxy,
C1-3alkoxycarbonyl, C1-4alkoxycarbonyl, C1-3aminocarbonyl,
With3-6cycloalkyl, C1-6heteroseksualci,
C1-6geterotsiklicheskikh, C1-6heterocyclizations,
C1-3aminocarboxylate, C1-10heteroaryl,6-10arylamino,
With6-10aryloxyalkyl,C1-3alkylsulfonamides, hydroxyaminobuteroyl, C1-3alkylsulfonyl,
C1-6heterocyclisation,
C1-6heterocyclizations,3-6cycloalkylcarbonyl,6-10allumination, C1-3aminosulfonyl,
C1-10heteroarylboronic, C1-3alkylcarboxylic,
C1-3alkylsulfonate or6-10arylsulfonamides,
each of which is optionally substituted by one or more identical or different substituents selected from such as hydroxy, -NH2mono - or di-(C1-6alkyl)amino, aminomethyl, carboxy, trifluoromethyl, cyano, fluorine, chlorine, iodine, oxo, mercapto, C1-4alkyl,
C1-3hydroxyalkyl, C1-3alkoxy, C1-4alkoxycarbonyl,
With3-6cycloalkyl,3-6heteroseksualci,
C geterotsiklicheskikh,6-10aryl, C1-10heteroaryl,
C1-3alkoxyl6-10aryl, C1-3alkylsulfonyl, -S(O)2OH or
C1-3alkylcarboxylic,
where specified3-6cycloalkyl, C1-4alkyl, C1-2alkoxy,
C1-4alkoxycarbonyl, C1-6heteroseksualci,6-10aryl or
C1-10heteroaryl are optionally additionally substituted carboxy, halogen, hydroxy, cyano, C1-6heterocyclization, one or more C1-6alkilani, C1-3alkoxy, C1-3alkoxyl1-3alkoxy, C1-4alkoxycarbonyl, C1-3hydroxyalkyl or6-10Allami.

9. The connection according to claim 7, where G represents phenyl, substituted with such substituents as iodine, fluorine, hydroxyethylpyrrolidine, ethylaminomethyl, dimethylaminoethylmethacrylate, pyrrolidinedione, amidino, aminohydrocinnamic, methoxycarbonyl, etoxycarbonyl, hydroxyethylaminomethyl, N-hydroxyethyl-N-methylaminomethyl, N-hydroxymethyl-N-propylaminoethyl, bishydroxycoumarin, dihydroxy-tert-butylaminoethyl, N-hydroxyethyl-N-ethylaminomethyl, cyanoethylation, morpholinosydnonimine, teretiarikare, differentillumination, methoxycarbonylaminophenyl, N-pyridylmethyl-N-methylamino boil, benzyloxycarbonyl, methylcarbamoylmethyl, iodinedeeciency, methoxyethylmercury, mercaptoethylamine, ethoxycarbonylmethylene, sulfoaluminate, dimethylaminoethyl, diethylaminoethylamine, dimethylaminopropylamine, piperidinylcarbonyl, methylpiperazine, hydroxyethylpiperazine, morpholinoethyl, hydroxypiperidine, imidazolidinylideneamino, carboxymethylaminomethyl, tert-butoxycarbonylmethylene, tert-butoxycarbonyloxyimino, methoxycarbonylaminophenyl, carboxymethylaminomethyl, methoxycarbonylaminophenyl, carboxypolymethylene, N-ethoxycarbonylmethyl-N-cyclohexyloxycarbonyl, diethoxycarbonylcyclohexaneoxime, tert-butoxycarbonyloxyimino, carboxymethylaminomethyl, carboxymethylaminomethyl, methoxyisobutylisonitrile, N,N-diterbakicinternational, carboxyethylgermanium, carboxymethylaminomethyl, carboxymethylaminomethyl, ethylcarboxylate, carboxylcontaining, carboxymethylaminomethyl, carboxybenzeneboronic, N-methyl-N-carboxymethylamino boil, carboxypropylbetaine, ethoxycarbonylpyrimidine, carboxypeptidases, N-ethoxycarbonylmethyl-N-cyclohexyloxycarbonyl, N-carboxymethyl-N-cyclohexyloxycarbonyl, externalinternal, cyanomethaemoglobin, cyanodithioiminocarbonate, phenylmethanesulfonyl, methoxycarbonylaminophenyl, ethoxycarbonylpyrimidine, carboxyhydroxymethyl, carboxyhydroxymethyl, tert-butoxycarbonyl, methoxyaminomethyl, tetrahydroquinoxaline, N-methoxy-N-methylaminomethyl, phenylmethanesulfonyl, hydroxyaminobuteroyl, morpholinobenzenediazonium, methylsulfonylmethane, methoxycarbonylpropionyl, carboxyhydroxymethyl, ethoxycarbonylmethoxy, methoxycarbonylethyl, carboxymethoxy, carboxyethyl, ethoxycarbonylmethyl, carboxymethoxy, oxopyrrolidin, oxoacridine, methylcobalamine, hydroxyethylaminophenol, imidazolyl, hydroxycyclopent, methylcarbamic, hydroxymethyl, hydroxycinnamates, diethoxycarbonyl, ethoxycarbonylmethyl, carboxymethyl, peroxyacyl, aminomethylphenol, cyclopropyl[1,2,4]oxadiazolyl, cyclopentyl[1,2,4]oxadiazolyl, methyl[1,2,4]oxadiazolyl, isopropyl[1,2,4]what xavator, tert-butyl[1,2,4]oxadiazolyl, cyclohexyl[1,2,4]oxadiazolyl, methylbutyl[1,2,4]oxadiazolyl, dioxoimidazolidin[1,2,4]oxadiazolyl, methoxazole[1,2,4]oxadiazolyl, dimethyloxazole[1,2,4]oxadiazolyl, cyanometallates, carboxymethylated, methylsulphonyl, methoxycarbonyl, hydroxymethyl, methylsulfonylamino, morpholinylcarbonyl, methylcarbamoylmethyl, hydroxyethylaminomethyl, methylsulfonylamino, morpholinylcarbonyl, methoxyethoxyethoxy, methoxyethoxyethoxy, ataxiatelangiectasia, dihydroxyprogesterone, tetrahydropyranyloxy, hydroxy, ethoxycarbonylmethoxy, carboxypropyl, carboxymethoxy, oxodegradable, ethoxyethoxy, ethoxycarbonylmethoxy, cyanophenylacetic, pyridyloxy, pyrazolidone, indolylacetic, carboxymethylate carboxyphenoxypropane, carboxyphenoxy, hydroxymethylpropane, hydroxycitrate dimethylaminocarbonylmethyl, hydroxymethylpropane, hydroxymethyluracil, dihydroxypropane, carboxypeptidase, hydroxyethoxy, hydroxyethylpyrrolidine, hydroxypyrrolidine, ethoxycarbonylmethyl, methyltetrahydrofolate, carboxy, ethoxy or hydroxypropyl.

10. The connection according to claim 9, where, when G is phenyl, optionally someseni is, Deputy attached to the phenylene ring in the meta or paraprotein towards the place where the phenyl ring attached to cycloalkyl represented by the formula.

11. The compound according to claim 1 or 2, where G represents C1-10heteroaryl or C1-6heteroseksualci and where specified C1-10heteroaryl or C1-6heteroseksualci is optionally substituted carboxy, C1-6the alkyl, C6-10the aryl, C1-3alkoxycarbonyl, which can be further optionally substituted by trifluoromethyl, halogen, C1-3the alkyl, C1-3alkoxy, C1-10heteroaryl, where C1-10heteroaryl can be optionally substituted C1-3the alkyl or oxo.

12. The connection section 12, where G represents tortenelem[1,2,4]oxadiazolyl, phenyl[1,2,4]oxadiazolyl, isopropyl[1,2,4]oxadiazolyl, triptoreline[1,2,4]oxadiazolyl, methyl[1,2,4]oxadiazolyl, methylthiazolidine[1,2,4]oxadiazolyl, propyl[1,2,4]oxadiazolyl, oxopyridine[1,2,4]oxadiazolyl, methoxyphenyl[1,2,4]oxadiazolyl, methylcarbamoylmethyl, ethoxycarbonylmethyl, ethoxycarbonylphenyl, pyridyl, carboxymethyl or carboxyphenyl.

13. The compound according to claim 1 or 2, where G is phenylamino or phenyloxy, optionally substituted by cyano, carboxy, C1-4alkoxycarbonyl or trifluoromethyl which M.

14. The compound according to claim 1 or 2, where R2, R3, R4and R5represent hydrogen.

15. The compound according to claim 1 or 2, where R1represents methyl.

16. The compound according to claim 1 or 2, where G represents C6-10aryl,
C1-3aminocarbonyl6-10aryl or C1-4alkyls6-10aryl, optionally substituted carboxy, C1-3alkoxy or C1-3alkoxycarbonyl, R4and R5represent hydrogen and R1represents methyl.

17. The compound according to claim 1, selected from the group consisting of these compounds, as
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid (compound 1000),
cyclobutyl-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1001),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, dimethylamide (compound 1002),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid amide (compound 1003),
(4-methylpiperazin-1-yl)[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano, hydrochloride (compound 1004),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, cyclopropylamine (compound 1005),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, Isopropylamine (compound 1006),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, propylamide (compound 1007),
morpholine-4-yl-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1008),
3-((R-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, tert-butylamide (compound 1009),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, ethylamide (compound 1010),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid methoxy-methyl-amide, hydrochloride (compound 1011),
[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)cyclobutyl]((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1012),
((R)-1-naphthalene-1-retil){3-[3-(3-triptoreline)[1,2,4]oxadiazol-5-yl]cyclobutyl}amine, hydrochloride (compound 1013),
[3-(3-methyl[1,2,4]oxadiazol-5-yl)cyclobutyl]((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1014),
((R)-1-naphthalene-1-retil)[3-(3-phenyl[1,2,4]oxadiazol-5-yl)cyclobutyl]amine, hydrochloride (compound 1015),
((R)-1-naphthalene-1-retil){3-[3-(4-triptoreline)[1,2,4]oxadiazol-5-yl]cyclobutyl}amine, hydrochloride (compound 1016),
{3-[3-(4-methoxyphenyl)[1,2,4]oxadiazol-5-yl]cyclobutyl)-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1017),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, 4-Chlorobenzilate (compound 1018),
{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}acetic acid, methyl ester (compound 1019),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (2-methoxyethyl)amide (compound 1020),
4-{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}benzoic acid, ethyl ester (compound 1021),
(2,6-dimethylmorpholine-4-yl)[3-((R)-naphtalen-1 ylethylamine)cyclobutyl]metano (compound 1022),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (3-morpholine-4-ylpropyl)amide (compound 1023),
1-[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]piperidine-4-carboxylic acid, ethyl ester (compound 1024),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (2-hydroxy-2-phenylethyl)amide (compound 1025),
3-{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}propionic acid ethyl ester (compound 1026),
[3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl][4-(3-triptoreline)piperazine-1-yl]metano (compound 1027),
{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid, methyl ester (compound 1028),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, (2-hydroxyine-1-yl)amide (compound 1029),
[4-(2-methoxyethyl)piperazine-1-yl][3-((R)-1-naphthalene-1-ylethylamine)cyclobutyl]metano (compound 1030),
3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl acid, 2,3,6-triptoreline (compound 1031),
3-({[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}methyl)benzoic acid, methyl ester (compound 1032),
4-({[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}methyl)benzoic acid, methyl ester (compound 1033),
{[3-((R)-1-naphthalene-1-ylethylamine)cyclobutanecarbonyl]amino}phenylacetic acid (soedinenii),
((R)-1-naphthalene-1-retil)(3-phenylcyclohexyl)amine (compound 1035 and 1036 connection),
{3-[3-(4-forfinal)[1,2,4]oxadiazol-5-yl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1037),
((R)-1-naphthalene-1-retil)-[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]amine, hydrochloride (compound 1038),
[3-(3-isopropyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1039),
((R)-1-naphthalene-1-retil)-{3-[3-(4-triptoreline)[1,2,4]oxadiazol-5-yl]cyclopentyl}amine, hydrochloride (compound 1040),
[3-(3-methyl-[1,2,4]oxadiazol-5-yl)cyclopentyl]((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1041),
{3-[3-(5-methylthiazole-2-ylmethyl)-[1,2,4]oxadiazol-5-yl]cyclopentyl}((R)-1-naphthalene-1-retil)amine (compound 1042),
((R)-1-naphthalene-1-retil)[3-(3-propyl[1,2,4]oxadiazol-5-yl)cyclopentyl]amine, hydrochloride (compound a and 1043b),
1-{5-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]-[1,2,4]oxadiazol-3-ylmethyl}-1H-pyridine-2-it, hydrochloride (compound 1044),
{3-[3-(4-methoxyphenyl)[1,2,4]oxadiazol-5-yl]cyclopentyl}((R)-1-naphthalene-1-retil)amine, hydrochloride (compound 1045),
3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid amide (compound 1046),
4-methyl-N-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl]benzosulfimide (connection a, the connection 1047b, the connection s and connection 1047d),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzene is home to the thrill (connection 1048/1049/1050),
N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1051),
N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1052),
N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection a and connection 1053b),
{3-[4-(aminopyrrolidine-1-ylmethyl)phenyl]cyclohexyl}((R)-1-naphthalene-1-retil)amine (compound 1054),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1055),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1056),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1057),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1058, a),
3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, ethyl ester (compound 1059),
N-(2-hydroxyethyl)-3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1060),
3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid (compound 1061/1062),
((R)-1-naphthalene-1-retil)-(3(S)-phenylcyclohexyl)amine (compound 1063),
((R)-1-naphthalene-1-retil)-(3(R)-phenylcyclohexyl)amine (compound 1064),
N-((R)-1-naphthalene-1-retil)-N'-phenylcyclohexane-1,3-diamine (compound 1065),
N-((R)-1-naphthalene-1-retil)-N'-(3-triptoreline)cyclohexane-1,3-diamine (compound 1066),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexylamino]benzonitrile (connection 1067),
((R)-1-naphthalene-1-retil)-(3-pyridin-2-illlogical)amine (compound 1069/1070),
5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]thiophene-2-carboxylic acid, ethyl ester (compound 1071),
5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]thiophene-2-carboxylic acid (compound 1072),
5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carboxylic acid, ethyl ester (compound 1073),
5-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]furan-2-carboxylic acid (compound a, the connection 1074b and connection s),
{3-[3-(4-forfinal)[1,2,4]oxadiazol-5-yl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1075),
((R)-1-naphthalene-1-retil){3-[3-(4-triptoreline)[1,2,4]oxadiazol-5-yl]cyclohexyl}amine (compound 1076),
((R)-1-naphthalene-1-retil)[3-(3-phenyl-[1,2,4]oxadiazol-5-yl)cyclohexyl]amine (compound 1077),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1078),
N-benzyloxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1079),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 4-itfinally ester (compound 1080),
2-{4-[3-((R)-1-naphthalene-1-ylethylamine) cyclohexyl]benzoylamine}econsultancy acid (compound 1081),
N-((R)-1-hydroxymethylpropane)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1082),
N-((S)-1-hydroxymethylpropane)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]ansamed (connection 1083),
N-(2-cyanoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1084),
N-(2-morpholine-4-retil)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1085),
N-(2-foradil)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1086),
N-(2,2-dottorati)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1087),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1088),
N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-pyridin-4-ylmethylene (connection 1089),
N-(2-dimethylaminoethyl)-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1090),
(2-hydroxyethylpyrrolidine-1-yl){4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1091),
N-(2-acetylamino)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1092),
N-ethyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1093),
N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1094),
N-(2-hydroxy-1-hydroxymethyl-1-methylethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1095),
N-(2-methoxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine) cyclohexyl] benzamide (connection 1096),
N-(2-mercaptoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1097),
{4-[3-((R)-1-naphtha is Jn-1 ylethylamine)cyclohexyl]benzoylamine}acetic acid, ethyl ester (compound 1098),
N,N-dimethyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1099),
N-(2-hydroxyethyl)N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1100),
N-ethyl-N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1101),
N,N-bis-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1102),
N-(2-dimethylaminoethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1103),
N-(3-dimethylaminopropyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1104),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}piperidine-1-ylmethanone (connection 1105),
(4-methylpiperazin-1-yl){4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1106),
[4-(2-hydroxyethyl)piperazine-1-yl]{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1107),
morpholine-4-yl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1108),
(4-hydroxypiperidine-1-yl){4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}mechanon (connection 1109),
N-(3-imidazol-1-ylpropyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (compound 1110),
3-((R)-1-naphthalene-1-ylethylamine)cyclopentanecarbonyl acid (compound 1111),
{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine)acetic sour is a (connection 1115),
(S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid, 4-tert-butyl ester, 1-methyl ester (compound 1116),
(S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}succinic acid, 4-tert-butyl ester (compound 1117),
(R)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid, methyl ester (compound 1118),
(R)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid (compound 1119),
(S)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid, methyl ester (compound 1120),
(S)-2-[4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}-3-phenylpropionate acid, hydrochloride (compound 1121),
(S)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1122),
(S)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1123),
(R)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1124),
(R)-3-(1H-indol-3-yl)-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1125),
(Ziklag the KSIL-{4-[3-(1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid, ethyl ester (compound 1126),
2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}malonic acid diethyl ester (compound 1127),
(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid tert-butyl ester (compound 1128),
5-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}nicotinic acid (compound 1129),
4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid (compound 1130),
4-methoxy-3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid, methyl ester, hydrochloride (compound 1131),
2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}benzoic acid, hydrochloride (compound 1132),
(carboxymethyl-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid, hydrochloride (compound 1133),
1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}methyl)cyclopentanecarbonyl acid (compound 1134),
1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopentanecarbonyl acid, hydrochloride (compound 1135),
3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid hydrochloride (compound 1136),
(1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cycle is hexyl)acetic acid, hydrochloride (compound 1137),
1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopropanecarbonyl acid, ethyl ester (compound 1138),
1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}cyclopropanecarbonyl acid (compound 1139),
1-({4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}methyl)cyclopropanecarbonyl acid (compound 1140),
2-methyl-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid (compound 1141),
1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}azetidin-3-carboxylic acid (compound 1142),
(methyl-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1143),
4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}butyric acid (compound 1144),
1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid, ethyl ester (compound 1145),
1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}piperidine-4-carboxylic acid (compound 1146),
(cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid ethyl ester (compound 1147),
(cyclohexyl-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}amino)acetic acid (compound 1148),
4-[(1S,3S)-3-((R)-1-naphthalene-1-Iletisim the but)cyclohexyl]-N-((R)-2-oxitetraciclina-3-yl)benzamide (connection 1149),
N-cyanomethyl-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1150),
N-(4-cyano-1H-pyrazole-3-yl)-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1151),
(R)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid, benzyl ester (compound 1152),
(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid, benzyl ester (compound 1153),
(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1154),
(R)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid methyl ester (compound 1155),
(S)-3-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid, ethyl ester, hydrochloride (compound 1156),
3-hydroxy-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}propionic acid hydrochloride (compound 1157),
(R)-4-hydroxy-2-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoylamine}butyric acid (compound 1158),
N-tert-butoxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, formate (compound 1159),
N-tert-butoxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, formate (compound 1160),
N-m is toxi-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine) cyclohexyl]benzamide, formate (compound 1161),
N-methoxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide; formate (compound 1162),
4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-(tetrahydrofuran-3-ylethoxy)benzamide (connection 1163),
4-[3-(R)-1-naphthalene-1-ylethylamine)cyclohexyl]-N-(tetrahydrofuran-3-ylethoxy)benzamide (connection 1164),
N-methoxy-N-methyl-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide, isformat (connection 1165),
N-methoxy-N-methyl-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1166),
N-benzyloxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1167),
N-benzyloxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1168),
N-hydroxy-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1169),
N-hydroxy-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1170),
N-(2-morpholine-4-yl-2-oksidoksi)-4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1171),
N-(2-morpholine-4-yl-2-oksidoksi)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzamide (connection 1172),
N-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}methanesulfonamide (connection 1173),
4R-hydroxy-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2S-carboxylic acid, methyl ester (compound 1174),
4R-hydroxy-1-{4-[(1S,3S)-3-(R)-1-Naftali is-1 ylethylamine)cyclohexyl]benzoyl}pyrrolidin-2S-carboxylic acid (compound 1175),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoyl}methanesulfonamide, hydrochloride (compound 1176),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid ethyl ester (compound 1177/1178),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid ethyl ester (compound 1179/1180),
3-{4-[(3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid methyl ester (compound 1181/1182/1183/1184),
{4-[3-(R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1185),
{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1186),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1187),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1188),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1189),
3-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1190),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1191),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1192),
{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid ethyl ester (compound 1193/1194/1195/1196),
3-{3-[3-((R)-1-naphthalin-ylethylamine)cyclopentyl]phenyl}propionic acid, ethyl ester (compound 1197/1198/1198/1200),
{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid, hydrochloride (compound 1201),
{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1202),
{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid (compound 1203),
3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1204),
3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1205),
3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1206),
3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid (compound 1207),
3-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propionic acid hydrochloride (compound 1208),
[3-(4-itfinal)cyclohexyl]((R)-1-naphthalene-1-retil)amine (compound 1209),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}pyrrolidin-2-on (compound 1210),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxazolidin-2-on (compound 1211),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}ndimethylacetamide (connection 1212),
4-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydropyran-4-ol (compound 1213),
[3-(4-imidazol-1-ylphenyl)cyclohexyl]((R)-1-naphthalene-1-retil)amine (compound 1214),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)C is clohessy]phenyl}Cyclopentanol (connection 1215),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}Etalon (connection 1216),
4-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}tetrahydropyran-4-ol, hydrochloride (compound 1217),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanol (compound 1218),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}cyclobutanol (connection 1219),
2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}malonic acid diethyl ester (compound 1220),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid ethyl ester (compound 1221),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}acetic acid (compound 1222),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}oxetan-3-ol (compound 1223),
{3-[4-(3-fluoro-oxetan-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1224),
{3-[4-(3-amino-3-methylbut-1-inyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1225),
{3-[4-(5-cyclopropyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1226),
{3-[4-(5-cyclopentyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1227),
{3-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1228),
{3-[4-(5-isopropyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1229),
{3-[4-(5-tert-butyl[1,2,4]about sedesol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1230),
{3-[4-(5-cyclohexyl-[1,2,4]oxadiazol-3-yl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine(compound 1231),
(3-{4-[5-(3-methylbutyl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1232),
5-(3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}-[1,2,4]oxadiazol-5-ylmethyl)imidazolidin-2,4-dione (compound 1233),
(3-{4-[5-(4-methoxazole-5-yl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1234),
(3-{4-[5-(2,5-dimethyloxazole-4-yl)-[1,2,4]oxadiazol-3-yl]phenyl}cyclohexyl)-((R)-1-naphthalene-1-retil)amine (compound 1235),
2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionitrile (connection 1236/1237),
2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1238),
2-methyl-2-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1239),
[3-(4-methanesulfonyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1240),
2-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, methyl ester (compound 1241),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanol (compound 1242),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}methanesulfonamide (connection 1243),
{3-[4-(morpholine-4-sulfonyl)phenyl]cyclohexyl}-((R)-1-naphthalene-1-retil)amine (compound 1244/1245),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]b is nil}ndimethylacetamide (connection 1246/1247),
3-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, methyl ester (compound 1248),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanesulfonamide (connection 1249/1250),
N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}methanesulfonamide (1251 connection),
N-(2-hydroxyethyl)-4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzosulfimide (connection 1252/1253),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenyl}propionic acid (compound 1254),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]phenoxy}acetic acid (compound 1255),
[3-(4-methanesulfonyl)cyclopentyl]-((R)-1-naphthalene-1-retil)amine (compound 1256/1257),
N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}methanesulfonamide (connection 1258/1259),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}ndimethylacetamide (connection 1260/1261),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzyl}ndimethylacetamide (connection 1262/1263),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzyl}methanesulfonamide (connection 1264/1265),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}methanesulfonamide (connection 1266/1267),
[3-(4-methanesulfonyl)cycloheptyl]-((R)-1-naphthalene-1-retil)amine (compound 1268),
2-fluoro-4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzoic acid, methyl ester (compound 1269),
N-{3-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]enyl}methanesulfonamide (connection 1270),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}ndimethylacetamide (connection 1271/1272),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzyl}ndimethylacetamide (connection 1273/1274),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]benzyl}methanesulfonamide (connection 1275/1276),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenoxy}acetic acid ethyl ester (compound 1277),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}propionic acid methyl ester (compound 1278/1279),
N-{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanesulfonamide (connection 1280/1281),
{3-[4-(morpholine-4-sulfonyl)phenyl]cycloheptyl}-((R)-1-naphthalene-1-retil)amine (compound 1282),
{4-[3-((R)-1-naphthalene-1-ylethylamine)cycloheptyl]phenyl}methanol (compound 1283),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, methyl ester (compound 1284),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, ethyl ester (compound 1285),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-morpholine-4-jatiluwih ester, dihydrochloride (compound 1286),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-(2-methoxyethoxy)ethyl ester, hydrochloride (compound 1287),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-[2-(2-methoxyethoxy)ethoxy]ethyl ester, hydrochloride (connection 1288),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2-[2-(2-ethoxyethoxy)ethoxy]ethyl ester, hydrochloride (compound 1289),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, 2,3-dihydroxypropyl ester, hydrochloride (compound 1290),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzoic acid, tetrahydrofuran-2-ymetray ester, hydrochloride (compound 1291),
4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenol (compound 1292),
2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid, ethyl ester (compound 1293),
2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1294),
2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid (compound 1295),
3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}dihydrofuran-2-on (compound 1296),
(S)-{3R-[4-(2-ethoxyethoxy)phenyl]cyclopentyl}-((R)-1-naphthalene-1-retil)amine (compound 1297),
3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid, ethyl ester (compound 1298),
4-(4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxymethyl}benzonitrile (connection 1299),
(S)-((R)-1-naphthalene-1-retil)-{3R-[4-(pyridine-3-ylethoxy)phenyl]cyclopentyl}amine (compound 1300),
(S)-((R)-1-naphthalene-1-retil)-{3R-[4-(2-pyrazole-1-ylethoxy)f the Nile]cyclopentyl}amine (compound 1301),
(S)-(3R-{4-[2-(1H-indol-3-yl)ethoxy]phenyl}cyclopentyl)-((R)-1-naphthalene-1-retil)amine (compound 1302),
2-methyl-2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid hydrochloride (compound 1303),
4-hydroxy-2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}butyric acid (compound 1304),
2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propionic acid hydrochloride (compound 1305),
{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}phenylacetic acid, hydrochloride (compound 1306),
2-methyl-1-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propan-2-ol (compound 1307),
3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxymethyl}pentane-3-ol (compound 1308),
dimethyl-karamanova acid 4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl ester (compound 1309),
3-ethyl-1-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}pentane-3-ol (compound 1310),
2-methyl-4-{4-[(1S,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}butane-2-ol (compound 1311),
3-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}propane-1,2-diol (compound 1312),
(2-forfinal)-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}acetic acid, hydrochloride (compound 1313),
2-{4-[(1R,3S)-3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenoxy}ethanol, formate (compound 1314),
(1-{4-[-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}pyrrolidin-2-yl)methanol (compound 1315),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}pyrrolidin-3-ol (compound 1316),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclohexyl]benzyl}piperidine-3-carboxylic acid, ethyl ester (compound 1317),
[3-(4-{[methyl(tetrahydrofuran-2-ylmethyl)amino]methyl}phenyl)cyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1318),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid, ethyl ester (compound 1335/1336),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1337),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoic acid (compound 1338),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoylamine}propionic acid methyl ester (compound 1339),
1-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoyl}piperidine-4-carboxylic acid, hydrochloride (compound 1340),
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]benzoylamine}propionic acid hydrochloride (compound 1341),
4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid, methyl ester (compound 1342),
4-[3R-((R)-1-naphthalene-1-ylethylamine)cyclopentyloxy]benzoic acid, formate (compound 1343),
5-methyl-3-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]-3H-imidazole-4-carboxylic acid (compound 1344),
5-(4-ethoxyphenyl-2-propylcyclohexyl]-((R)-1-naphthalene-1-retil)amine (compound 1346)
what do
3-{4-[3-((R)-1-naphthalene-1-ylethylamine)cyclopentyl]phenyl}propan-1-ol (compound 1348).

18. Intermediate compound for producing compounds according to claim 1, selected from the group consisting of these compounds, as
3-[3-(3-triptoreline)-[1,2,4]oxadiazol-5-yl]cyclobutanol (connection 1112),
4-methyl-N-(3-oxocyclopentanecarboxylate)benzosulfimide (connection 1113),
3-(3-triptoreline)amino-cyclohexanone (compound 1114),
3-((R)-1-naphthalene-1-ylethylamine)cyclohexanecarbonyl acid (preparation 4),
3-(4-itfinal)cyclohexane-1-he (preparation 5),
4-(3-oxocyclohexyl)benzaldehyde (preparation 7),
3-[4-((1S)-3-oxocyclopent)phenyl]propionic acid, ethyl ester (preparation 8),
3-[4-((1S,3R)-3-acetoxyacetyl)phenyl]propionic acid, ethyl ester (preparation 9),
3-[4-((1S,3R)-3-hydroxycyclopent)phenyl]propionic acid, ethyl ester (preparation 10),
3-[4-((1S,3R)-3-methanesulfonylaminoethyl)phenyl]propionic acid, ethyl ester (preparation 11),
4-((1S,4S)-4-acetoxysilane-2-enyloxy)benzoic acid, methyl ester (preparation 13),
4-((1S,4S)-4-hydroxycyclopent-2-enyloxy)benzoic acid, methyl ester (preparation 14),
4-((1S,4R)-4-harcelement-2-enyloxy)benzoic acid, methyl ester (preparation 15),
4-[(1S,4S)-4-((R)-1-naftol the n-1 ylethylamine)cyclopent-2-enyloxy]benzoic acid, methyl ester (preparation 16),
3-((1S,4S)-4-acetoxysilane-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 17),
3-((1S,4S)-4-hydroxycyclopent-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 18),
3-((1S,4R)-4-harcelement-2-enyl)-5-methyl-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 19) or
5-methyl-3-[(1S,4S)-4-((R)-1-naphthalene-1-ylethylamine)cyclopent-2-enyl]-3H-imidazole-4-carboxylic acid, ethyl ester (preparation 20).

19. The use of compounds according to any one of claims 1 to 17 as a medicinal product having the properties of CaSR modulator.

20. The use of compounds according to any one of claims 1 to 17 for the treatment, alleviation or prophylaxis of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism.

21. The use of compounds according to any one of claims 1 to 17 for the manufacture of a medicinal product for the prevention, cure or relief of physiological disorders or diseases associated with disturbances of CaSR activity, such as hyperparathyroidism.

22. Pharmaceutical composition having the properties of a CaSR modulator, containing an effective amount of a compound according to any one of claims 1 to 17 or its pharmaceutically acceptable salt or hydrolyzable in vivo ester in the natural with a pharmaceutically acceptable carrier or excipient.

23. A method of preventing, treating or alleviating cancer of the parathyroid gland, adenoma of the parathyroid gland, the primary hyperplasia of the parathyroid gland, heart, kidney or intestinal dysfunctions, diseases of the Central nervous system, chronic renal failure, chronic renal disease associated with podocyte disease, primary hyperparathyroidism, secondary hyperparathyroidism, tertiary hyperparathyroidism, anemia, cardiovascular diseases, fibrotic generalized Ostia, adinamicheskoy disease of bone, osteoporosis caused by steroid osteoporosis, senile osteoporosis, postmenopausal osteoporosis, osteomalacia and related bone disorders, bone loss after kidney transplantation, gastrointestinal diseases, endocrine and neurodegenerative diseases, cancer, Alzheimer's disease, hypercalcemia or bone diseases associated with kidney disease, comprising administration to a patient in need, an effective amount of a compound according to any one of claims 1 to 17.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I and formula IV wherein the radical values are such as specified in cl. 1 and 4 of the patent claim, as well as to their therapeutically acceptable salts. Besides, the invention refers to a composition for treating cancer on the basis of the compounds of formula I, to using the compounds of formula I for preparing the therapeutic agent for treating cancer, as well as to using it for treating cancer.

EFFECT: there are prepared and described the new compounds which inhibit anti-apoptotic Bcl-2 and Bcl-x protein activity.

17 cl, 481 ex

.FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I) and their physiologically acceptable salts also possessing properties for decrease the blood sugar content. In compound of the formula (I) A means phenyl wherein phenyl residue can be substituted up to three times with fluorine (F), chlorine (Cl) and bromine (Br) atoms; R1 and R2 mean hydrogen atom (H); R3, R4, R5 and R6 mean independently of one another H, F, Cl, Br, -NO2, -O-(C1-C6)-alkyl, (C1-C6)-alkyl, -COOH; R7 means H, (C1-C6)-alkyl wherein alkyl can be substituted up to three times with -OH, -CF3, -CN, COOH, -COO-(C1-C6)-alkyl, -CO-NH2, -NH2, -NH-(C1-C6)-alkyl, -N-[(C1-C6)-alkyl]2, -NHCO-(C1-C6)-alkyl, -NHCOO-(C1-C6)-alkyl or -NHCOO-(C1-C4)-alkylenephenyl; in (CH2)m m can mean 0-6 and aryl means phenyl, O-phenyl, CO-phenyl, benzo[1,3]dioxolyl, pyridyl, indolyl, piperidinyl, tetrahydronapthyl, 2,3-dihydrobenzo[1,4]dioxynyl, benzo[1,2,5]thiadiazolyl, pyrrolidinyl, morpholinyl wherein aryl residue can be substituted mono- or multiple with R9 wherein R9 means F, Cl, Br, -OH, -NO2, -CF3, -OCF3, (C1-C6)-alkyl, (C1-C6)-alkyl-OH, -O-(C1-C6)-alkyl, -COOH, -COO-(C1-C6)-alkyl. Also, invention relates to a pharmaceutical composition and a method for preparing a medicinal agent.

EFFECT: valuable medicinal properties of derivatives and pharmaceutical composition.

7 cl, 2 sch, 1 tbl, 293 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to novel [(heterylonio)-methylcarbonyloxypoly(alkyleneoxy)]-[(ammonio)methylcarbonyloxypoly(alkyleneoxy)]propane trichlorides of the general formula: wherein: at X+ = Y+ means X+ means -N+R1R2R3 wherein R1 = R2 means hydrogen atom (H); R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e (total degree of oxypropylation) = 49; b + d + f (total degree of oxyethylation) = 9; at X+ = Y+ means Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 10; at X+ means Y+ = Z+ means -N+R1R2R wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 49; b + d + f = 9; at X+ means Y+ = Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 10; at X+ means Y+ = Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 49; b + d + f = 0; at X+ means Y+ = Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 0; at X+ = Y+ means Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 49; b + d + f = 0; at X+ = Y+ means Z+ means -N+R1R2R3 wherein R1 = R2 means H; R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms; a + c + e = 55; b + d + f = 0, and to a method for their synthesis. Method involves interaction of 1,2,3-tris-[hydroxypoly(alkyleneoxy)]propane of the formula: wherein a + c + e = 55; b + d + f = 0-10 with monochloroacetic acid in the presence of acid catalysts, in organic solvent medium and with azeotropic removal of formed water and the following treatment at heating of the synthesized reaction productwith a mixture of morpholine and aliphatic amine in the molar ratio of reagents - hydroxyl derivative of propane: monochloroacetic acid : morpholine : aliphatic amine = 1:(3.0-3.2):(1.0-2.1):(1.0-2.1), respectively and wherein the total amount of morpholine and aliphatic amine is 3.0-3.2 mole. Novel compounds possess emulsifying properties for aqueous-bitumen and aqueous-mazut emulsions.

EFFECT: improved method of synthesis, valuable properties of compounds.

6 cl, 2 tbl, 8 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to novel 1,2,3-tris-[(ammonio)methylcarbonyloxypoly(alkyleneoxy)]-propane trichlorides of the general formula:

wherein at -X+ as -N+R1RR, R1 = R2 mean hydrogen atom (H), R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e (the general degree of oxypropylation) = 49,b + d + f (the general degree of oxyethylation) = 0; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e = 55, b + d + f = 0; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e = 80, b + d + f = 24; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, a + c + e = 90, b + d + f = 27; at -X+ as -N+R1R2R3, R1 = R2 means H, R3 means phenyl, a + c + e = 80, b + d + f = 24; at -X+ as -N+R1R2R3, R1 = R2 mean H, R3 means phenyl, a + c + e = 90, b + d + f = 27; at -X+ as , a + c + e = 80, b + d + f = 24; at -X+ as , a + c + e = 90, b + d + f =27. Also, invention relates to a method for synthesis of these compounds. Method involves interaction of 1,2,3-tris-[hydroxypoly(alkyleneoxy)]-propane of the formula:

wherein a + c + e = 49-90, b + d + f = 0-27 with monochloroacetic acid in the presence of acidic catalyst, in boiling organic solvent medium with azeotropic removal of water formed and the following treatment of synthesized reaction product in polar solvent medium at heating with amino-compounds of the formula: NR1R2R3 wherein R1 = R2 mean H, R3 means aliphatic hydrocarbon radical comprising 10-16 carbon atoms, phenyl, or morpholine of the formula:

in the following mole ratios of reagents - propane hydroxyl derivative : monochloroacetic acid : amino-compound or morpholine = 1:(3.0-3.2):(3.0-3.2), respectively. New compounds show the bactericidal and fungicide activity and properties of demulsifying agents for petroleum emulsions.

EFFECT: improved method of synthesis, valuable properties of compounds.

7 cl, 3 tbl, 8 ex

The invention relates to new derivatives benzoylpyridine General formula (I), where R1means alkyl with 1-8 carbon atoms, a represents a group represented by the formula of the invention, means (-CH2-)aor (-CO-)band means an integer of 0 to 8, preferably 1, 2, 3 or 4, b means of 0,1 or 2, preferably 1, R2means unsubstituted or substituted alkyl with 1-8 carbon atoms, unsubstituted phenyl, NR3R4or preferably the five-membered heterocycle represented in the claims, in which U, V, W, X and Z can mean CH, NH, O or S, R3and R4denote alkyl with 1-8 carbon atoms

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to novel compounds of formula (V), compounds of formula (IX), compounds of formula (XIII) or their tautomers or pharmaceutically acceptable salts, which are capable of inducing Hsp70, as well as to pharmaceutical composition, which contains claimed compounds.

Value of substituents in formulas (V), (IX) and (XIII) are such, as claimed in invention formula.

EFFECT: obtaining pharmaceutically acceptable salts, which have possibility of inducing Hsp70.

12 cl, 12 ex, 36 dwg, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new phenyl derivatives with the formula (I) where # symbol indicates two carbon atoms of the phenyl ring bearing R1, R2 and R3; to each of the latter components the A group can be linked; and where A represents or where asterisks indicate the link through which the formula (I) is linked to the phenyl ring bearing R1, R2 and R3; R1 represents hyndrogen or C1-3-alkyl; R2 represents C2-5-alkyl or C1-4-alkoxy group; R3 represents hydrogen, and in case when the A group is linked in the para-position in relation to the phenyl ring of the formula (I) bearing R1, R2 and R3, R3 can additionally represent the methyl group; R4 represents hydrogen; R5 represents C1-3-alkyl; R6 represents a hydroxy group, di-(hydroxy-C1-4-alkyl)-C1-4-alkoxy group, 2,3-dihydroxypropoxy group, -OCH2-CH(OH)-CH2-NR61R62 or -OCH2-CH(OH)-CH2-NHCOR64; R61 represents hydrogen; R62 represents hydrogen; R64 represents hydroxymethyl; and R7 represents C1-3-alkyl; and to its salt. The invention also refers to the pharmaceutical composition that is agonistic in relation to S1P1/EDG1 receptor on the basis of the mentioned compounds.

EFFECT: new compounds and the pharmaceutical composition based on them that may find their application in medicine as immunomodulating agents.

18 cl, 2 tbl, 28 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I): where R1 and R2 represent hydrogen and a group which is hydrolysed in a physiological environment, optionally substituted lower alkanoyl or aroyl; X represents a methylene group; Y represents oxygen atom; n represents the number 0, 1, 2 or 3 and m represents the number 0 or 1; R3 represents a group of pyridine N-oxide according to formula A, B or C which is attached as shown by an unmarked linking: where R4, R5, R6 and R7 independently represent aryl, heterocycle, hydrogen, C1-C6-alkyl, C1-C6-alkylthio, C6-C12-aryloxy or C6-C12-arylthio group, C1-C6-alkylsulphonyl or C6-C12-arylsulphonyl, halogen, C1-C6-haloalkyl, trifluoromethyl, or heteroaryl group; or where two or more residues R4, R5, R6 and R7 taken together represent an aromatic ring, and where P represents a central part, preferentially chosen from regioisomers 1,3,4-oxadiazol-2,5-diyl, 1,2,4-oxadiazol-3,5-diyl, 4-methyl-4H-1,2,4-triazol-3,5-diyl, 1,3,5-triazine-2,4-diyl, 1,2,4-triazine-3,5-diyl, 2H-tetrazol-2,5-diyl, 1,2,3-thiadiazol-4,5-diyl, 1-alkyl-3-(alkoxycarbonyl)-1R-pyrrol-2,5-diyl, where alkyl is presented by methyl, thiazol-2,4-diyl, 1H-pyrazol-1,5-diyl, pyrimidine-2,4-diyl, oxazol-2,4-diyl, carbonyl, 1H-imidazol-1,5-diyl, isoxazol-3,5-diyl, furan-2,4-diyl, benzole-1,3-diyl and (Z)-1-cyanoethene-1,2-diyl, and where the regioisomers of the central part include both regioisomers produced by exchanging the nitrocatechol fragment and the -(X)n-(Y)m-R3 fragment. Also, the invention refers to a method for making a compound of formula I, as well as to a method for treating an individual suffering central and peripheral nervous system disorders, to a pharmaceutical composition based on the compounds of formula I, and also to their application for preparing the drug and as COMT inhibitor.

EFFECT: there are produced and described new compounds which show a potentially effective pharmaceutical properties in treating a number of central and peripheral nervous system disorders.

25 cl, 64 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula as well as separate enantiomers, diastereomers, racemic mixures and pharmaceutically acceptable salts thereof, having mitotic kinesin KSP inhibiting activity, as well as inhibitory action on tumour cells, use thereof in preparing a medicinal agent and a pharmaceutical composition based on said compounds. In said formula, R denotes Z-NR2R3, Z-OH, Ar1 and Ar2 independently denote a phenyl which, if needed, is substituted with one or more groups independently selected from: F, CI, Br, I, OH, Z denotes an alkylene having 1-6 carbon atoms which, if needed, is substituted with C1-6alkyl, and R1 assumes values given in the claim.

EFFECT: improved method.

16 cl, 3 dwg, 124 ex

FIELD: medicine.

SUBSTANCE: invention relates to novel compounds of formula or to its pharmaceutically acceptable salts, where n is 0 or 1; R1 represents H or F; R2 represents C1-4alkyl; R7 represents H or C1-4alkyl; and Z represents hydroxyl C1-6alkyl or C1-6alkoxycarbonyl, or 5- or 6-member heteroaromatic ring, which belongs to aromatic rings which have given number of atoms, of which at least one is N, O or S, the remaining being carbon atoms, and which also optionally has methyl substituting group. Invention also relates to pharmaceutical composition, to application of compounds, as well as to method of obtaining formula I compounds.

EFFECT: obtaining novel biologically active compounds, possessing activity of receptor 5-HT2A antagonists.

9 cl, 25 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a malononitrile compound with formula (I): where one of X1, X2, X3 and X4 stands for CR100, where R100 is a group with formula (II) each three of the other X1, X2, X3 and X4 is nitrogen or CR5, under the condition that, from one to three of X1, X2, X3 and X4 stands for nitrogen, Z is oxygen, sulphur or NR6. The malononitrile compound can be used a pesticide in agriculture.

EFFECT: obtaining a new pest control compound and its use as an active ingredient of a pesticide composition.

18 cl, 180 ex

FIELD: organic chemistry, chemistry of heterocyclic compounds.

SUBSTANCE: invention relates to heterocyclic compounds possessing the potential biological activity, in particular, to a method for synthesis of 2-methyl-5-substituted 1,3,4-oxadiazoles. Invention describes a method for synthesis of 2-methyl-5R-substituted 1,3,4-oxadizoles wherein R means aryl, hetaryl or alkyl by the cyclization reaction of tributylstannyl derivatives of tetrazole in the presence of aliphatic acid anhydrides by the following scheme: . Method provides preparing 2-methyl-1,3,4-oxadiazoles substituted with bulky substitutes at position 5 by simplified technology.

EFFECT: improved and simplified method of synthesis.

8 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivatives of 5-amidino-2-hydroxybenzenesulfonamide of the general formula (I): wherein R2 means hydrogen atom (H), lower alkyl that can comprise a substitute chosen from the group (A): wherein (A) means -COORA, -CONRBRC, 3-7-membered monocyclic heterocycloalkyl group comprising one or two heteroatom in ring chosen from atoms N, O, S that can comprise oxo-group and 5-6-membered monocyclic aromatic heterocyclic group comprising one-three heteroatoms in ring chosen from atoms N, O, S that can comprise oxo-group or lower alkyl wherein RA means hydrogen atom (H), 3-7-membered monocyclic aliphatic alkyl group, lower alkyl that can comprises a substitute chosen from the group (i) wherein (i) means -COORA1 wherein RA1 means hydrogen atom (H), -OCORA2 wherein RA2 means lower alkyl group, -OCOORA3 wherein RA3 means lower alkyl, -ORA4 wherein RA4 means hydrogen atom (H), lower alkyl -CONRA5RA6 wherein RA5 and RA6 mean independently hydrogen atom (H), lower alkyl, or -NRA5RA6 forms 5-6-membered monocyclic amino-group comprising one heteroatom in ring chosen from atoms N, O, S and another one distinct from nitrogen atom (N) instead a bond; wherein RB and RC mean independently hydrogen atom (H), lower alkyl that can comprise a substitute chosen from the group (ii), or -NRBRC forms 5-6-membered monocyclic amino-group comprising one heteroatom in ring chosen from atoms N, O, S and another one distinct from nitrogen atom (N) instead a bond; (ii) means -COORB1 wherein RB1 means hydrogen atom (H), lower alkyl; T means oxygen atom (O), sulfonyl group; or TR1 means -SO2NRB3RC3 wherein RB3 and RC3 means independently hydrogen atom (H), lower alkyl; R2 means lower alkyl, phenyl that can comprise one-three substitutes chosen from the group (B) wherein (B) means halogen atom, -COORE, sulfamoyl, lower alkylsulfonyl wherein RE means lower alkyl; Q means hydrogen atom (H), lower alkyl that can comprise a substitute chosen from the group (D) wherein (D) means 5-6-membered monocyclic aromatic heterocyclic group that can comprise one-three heteroatom chosen from atoms N, O, S that can comprise a substitute chosen from the group (iv) wherein (iv) means oxo-group, lower alkyl; Z means hydrogen atom (H), hydroxyl group (OH), -COORN wherein RN means lower alkyl that can comprise a substitute chosen from the group (viii) wherein (viii) means -OCOR5 wherein RN5 means lower alkyl that can comprise -OCORN51 wherein RN51 means lower alkyl; or its pharmaceutically acceptable salt. Compounds of the formula (I) inhibit activated factor X in blood coagulation system that allows their using in pharmaceutical composition. Also, invention describes intermediate compounds.

EFFECT: valuable medicinal properties of compounds and compositions.

12 cl, 5 tbl

The invention relates to new substituted phenyl derivatives, which are strong blockers chlorine ion channels and as such are useful in the treatment of sickle cell anemia, cerebral edema that accompanies ischemia or tumor, diarrhea, hypertension (diuretic), osteoporosis and to reduce the intraocular pressure for the treatment of disorders such as glaucoma

The invention relates to a new above-mentioned compounds, method of their production and the means of containing this compound, useful for combating fungi and insect pests

FIELD: chemistry.

SUBSTANCE: present invention describes novel compounds of formula (I), where substitutes R1, R2, R3, Ar and A are described in the formula of invention, having histone deacetylase inhibiting activity, use thereof and methods for synthesis of said compounds.

EFFECT: improved composition properties.

15 cl, 72 ex, 9 tbl, 6 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to compound of formula (I), in which A1, A2, A3 and A4 independently on each other stand for C-X; each X independently stands for hydrogen; R1 and R2 independently on each other stand for hydrogen; G1 and G2 stand for oxygen; Q1 stands for phenyl or phenyl, containing from 1 to 2 substituents R3, which can be similar or different, or Q1 stands for pyridyl, containing one substituent R3; Q2 stands for phenyl or phenyl, containing from 1 to 2 substituents R4, which can be similar or different; each R3 independently stands for halogen, cyanogroup; each R4 independently stands for halogen, C1-C4-alkyl, C1-C4-halogenalkyl; R5 stands for C1-C4-perfluoroalkyl; Y1 and Y4 independently on each other stand for halogen, C1-C4-alkyl; and Y2 and Y3 stand for hydrogen; or its salt or N-oxide. Invention also relates to formula (II') compound. Formula (I) compounds are often used in insecticidal, acaricidal, nematocidal or molluskocidal compositions and methods of fighting insects, mites and ticks, nematodes or mollusks and their extermination.

EFFECT: bisamide derivatives as insecticidal compounds.

5 cl, 4 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an improved method of producing phenylalanine with a quinazolinedione ring of formula (1) or a pharmaceutically acceptable salt thereof, which can be used to produce a medicinal agent for treating inflammatory diseases whose pathology involves an α-4-integrin-dependent adhesion process, such as arthritis, inflammatory enteritis,multiple sclerosis etc. In formula (1), R1 is a phenyl group which can contain a substitute; R2 is an alkyl group which can contain a substitute; R3 is an alkyl group which is substituted with a dialkylamino group, an alkyl group which is substituted with a monoalkylamino group or an alkyl group which is substituted with an amino group; and R4 is a hydrogen atom, an alkyl group or a benzyl group which can contain a substitute. The method involves the following steps: (a) reaction of an acylphenylalanine derivative of formula (2), (3), with a reactant which introduces a carbonyl group or an anthranilic acid derivative of formula (3), where R1 and R2 have values given above, and R3' has values R3 which can have a protective group to form a urea derivative with asymmetrically lying carboxy group of formula (4), or a chemically acceptable salt thereof: (4), (5), (b) converting the urea derivative with asymmetrically lying carboxy groups of formula (4) to a quinazolinedione derivative of formula (5), or a pharmaceutically acceptable salt thereof, in the presence of an agent which activates the carboxyl group, where R1-R3' assume the same values given above; and (c) subsequent N alkylation of the compound of formula (5) and removing the protective group if necessary. The invention also relates to novel intermediate products.

EFFECT: method simplifies the process by cutting the number of steps and enables to obtain products with high output.

9 cl, 22 ex

FIELD: pharmaceutics.

SUBSTANCE: invention concerns novel compounds of the formula I , where R3 is (4-methylpiperazinyl)methyl and the other four radicals R1, R2, R4, and R5 are independently hydrogen; cyano; lower alkyl; hydroxy- or amino-substituted simple alkyl; trifluoromethyl; free or etherified hydroxy-group; (lower)alkoxy; (lower)alkanoyloxy; free, alkylated or acylated amino group; mono- or di(lower)alkylamino; (lower)alkanoylamino; benzoylamino; free or etherified carboxy-group; (lower)alkoxycarbonyl, and halogen; R6 is halogen, NH2, NO2, NHC(O)CF3, NHC(O)CH3 or NHC(NH)NH2, R7 is methyl, and R8 is hydrogen; or the compound salt, or crystalline form, method of obtainment, application in obtaining compound of the formula IV, and pharmaceutical composition for leukemia treatment, based on the claimed compounds.

EFFECT: novel compounds applicable in obtaining compounds inhibiting tyrosine kynase of epidermal growth factor (EGF) receptor.

13 cl, 12 ex

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