Heteroaryl-substituted piperidine derivatives as hepatic carnitine palmitoyltransferase (l-cpt1) inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) , where X is C(R8R9), NR10, O, S; R1 is phenyl which is substituted with 1-3 substitutes selected from a group which includes halogen, hydroxy group, lower alkyl, hydroxy-lower alkyl and CN; R2 is hydrogenor lower alkyl; R3 and R4 are hydrogen; R5 and R6 are hydrogen; R7 is oxadiazolyl or triazolyl, where oxadiazolyl or triazolyl is substituted with R11; R8 and R9 denote hydrogen; R10 denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl, R11 denotes aryl or hetearyl, selected from a group comprising pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-one, oxadiazolyl, indazolyl, 1,3-dihydrobenzimidazol-2-one, 1,3-dihydroindol-2-one, benzotriazolyl, imidazopyridinyl, triazolepyridinyl, tetrazolepyridinyl, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidin-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidin-2,4-one, benzoxazin-3-one, 1,4-dihydrobenzoxazin-2-one, indolyl, thiophenyl, oxazolyl, benzooxazin-2-one; 3,4-dihydroquinazolin-2-one, pyridazinyl, quinoxalinyl, benzothiazolyl, benzothiadiazolyl, naphthyridinyl, cinnolinyl, 1,4-dihydroquinoxalin-2,3-dione and 1,2-dihydroindazol-3-one, where the aryl or heteroaryl is optionally substituted with 1-3 substitutes selected from a group which includes lower alkyl, hydroxy group, B(OH)2, carboxy-lower alkoxy group, carbamoyl-lower alkoxy group, cyano group, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxy group, halogen, S(O2)R13, C(O)R14, NO2, NR15R16, phenyl-lower alkoxy group, [1,3,4]oxadiazol-2-one, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl, where imidazolyl is optionally substituted with lower alkyl, and where isoxazolyl is substituted with lower alkyl; R12 denotes hydrogen or lower alkyl; R13 denotes lower alkyl, NR17R18 or fluoro-lower alkyl; R14 denotes NR19 R20, lower alkoxy group, lower alkenyl-oxy group or lower alkyl; R15 and R16 independently denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or NR15R16 denotes heterocyclyl selected from a group which includes morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, piperidinyl, piperidin-2-one, piperazin-2-one, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperazinyl, pyrrolidinyl, 1,1-dioxoisothiazolidinyl, pyrrolidin-2-one, imidazolidine-1,4-dione, 2,4-dihydro[1.2.4]triazol-3-one, pyrrolidine-2,5-dione, azetidin-2-one and 1,3-dihydroimidazol-2-one, where the heterocycle is optionally substituted with hydroxy-lower alkyl or lower alkyl-carbonyl; R17 and R18 independently denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl; or NR17 R18 denotes morpholinyl; R19 and R20 independently denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxy group-lower alkyl or cyano-lower alkyl; or NR19 R20 denotes heterocyclyl selected from a group which includes morpholinyl, pyrrolidinyl, 8-oxa-3-aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinyl, piperazin-2-one, thiazolidinyl, thiomorpholinyl, 1,3,8-triaza-spiro[4.5]decane-2,4-dione and spiro(1- phthalan)piperidin-4-yl, where the heterocyclyl is optionally substituted with a hydroxy group, lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl or lower alkoxy group, carboxyl group, carbamoyl, cyano group and phenyl; and to their pharmaceutically acceptable salts. Invention also pertains to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds which inhibit hepatic carnitine palmitoyltransferase 1 (L-CPT1).

35 cl, 565 ex, 10 tbl

 

The text descriptions are given in facsimile form.

1. The compounds of formula (I)
,
where X is C(R8R9), NR10, O, S;
R1denotes phenyl, optionally substituted from 1 to 3 substituents selected from the group comprising halogen, a hydroxy-group, lower alkyl, hydroxy-lower alkyl and CN;
R2indicates vodor the d or lower alkyl;
R3and R4represent hydrogen;
R5and R6represent hydrogen;
R7means oxadiazolyl or triazolyl, while oxadiazolyl or triazolyl substituted R11;
R8and R9represent hydrogen;
R10denotes hydrogen, lower alkyl, lower alkyl-carbonyl or lower alkyl-sulfonyl;
R11denotes aryl or heteroaryl selected from the group including pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-it, oxadiazolyl, indazoles, 1,3-dehydrobenzperidol-2-he, 1,3-dihydroindol-2-it, benzotriazolyl, imidazopyridines, triazolopyridines, tetrasulphides, benzimidazolyl, 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidine-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzoxazin-3-one, 1,4-dihydrobenzoic-2-he, indolyl, thiophenyl, oxazolyl, benzoxazin-2-it, 3,4-dihydroquinazolin-2-it, pyridazinyl, honokalani, benzothiazolyl, benzotriazolyl, naphthyridine, cinnoline, 1,4-dihydroquinoxaline-2,3-dione and 1,2-dihydroindol-3-one, where the aryl or heteroaryl optionally substituted from 1 to 3 substituents selected from the group comprising lower alkyl, hydroxy-group, IN(OH)2, carboxy-lower alkoxygroup, carbarnoyl-lower alkoxygroup, cyano, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxygroup, halogen, S(O2R13C(O)R14N 2, NR15R16, phenyl-lower alkoxygroup, [1,3,4]oxadiazol-2-it, oxadiazolyl, triazolyl and isoxazolyl, imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl where imidazolyl optionally substituted lower alkyl, and where isoxazolyl substituted lower alkyl;
R12denotes hydrogen or lower alkyl;
R13denotes lower alkyl, NR17R18or fluoro-lower alkyl;
R14denotes NR19R20, lower alkoxygroup, lower alkenyl-oxygraph or lower alkyl;
R15and R16independently of one another denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl and lower alkyl-NH-carbonyl; or
NR15R16means heterocyclyl selected from the group comprising morpholinyl, thiomorpholine, 1,1-dioxothiazolidine, piperidine, piperidine-2-it, piperazine-2-it, 8-oxa-3-Aza-bicyclo[3.2.1]octyl, piperazinil, pyrrolidinyl, 1,1-dioxothiazolidine, pyrrolidin-2-it, imidazolidin-2,4-dione, 2,4-dihydro[1,2,4]triazole-3-one, pyrrolidin-2,5-dione, azetidin-2-he and 1,3-dihydroimidazole-2-it, where heterocyclyl optionally substituted hydroxy-lower alkyl or lower alkyl-carbonyl;
R17and R18independently of one another denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxygroup-lower alkyl; or
NR17R18 denotes morpholinyl;
R19and R20independently of one another denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxygroup-lower alkyl or cyano-lower alkyl; or
NR19R20means heterocyclyl selected from the group comprising morpholinyl, pyrrolidinyl, 8-oxa-3-Aza-bicyclo[3.2.1]octyl, piperidinyl, piperazinil, piperazine-2-it, diazolidinyl, thiomorpholine, 1,3,8-triaza-Spiro[4,5]decane-2,4-dione and Spiro(1-phthalan)piperidine-4-yl, where heterocyclyl optionally substituted by a hydroxy-group, the lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl or lower alkoxygroup,
a carboxyl group, carbamoyl, cyano and phenyl;
and their pharmaceutically acceptable salts.

2. Compounds according to claim 1,
where X denotes C(R8R9), NR10, O, S, S(O), S(O2);
R1denotes phenyl, optionally substituted from 1 to 3 substituents selected from the group comprising halogen, a hydroxy-group, lower alkyl, hydroxy-lower alkyl and CN;
R2denotes hydrogen or lower alkyl;
R3and R4represent hydrogen;
R5and R6represent hydrogen;
R7means oxadiazolyl or triazolyl, while oxadiazolyl or triazolyl substituted R11;
R8and R9represent hydrogen;
R10denotes hydrogen, lower alkyl, lower alkyl-it is bonil or lower alkyl-sulfonyl;
R11denotes aryl or heteroaryl selected from the group including pyridinyl, pyrazinyl, pyrimidinyl, pyridinyl-2-it, oxadiazolyl, indazoles, 1,3-dehydrobenzperidol-2-he, 1,3-dihydroindol-2-it, benzotriazolyl, imidazopyridines, triazolopyridines, tetrasulphide and benzimidazolyl, where the aryl or heteroaryl optionally substituted from 1 to 3 substituents selected from the group comprising lower alkyl, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxygroup, halogen, S(O2R13C(O)R14, NO2, NR15R16imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl and phenyl-lower alkoxygroup where imidazolyl optionally substituted lower alkyl;
R12denotes hydrogen or lower alkyl;
R13denotes lower alkyl, NR17R18or fluoro-lower alkyl;
R14denotes NR19R20, lower alkoxygroup or lower alkenyl-oxygraph;
R15and R16independently of one another denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxy-carbonyl, lower alkyl-NH-carbonyl; or
NR15R16means heterocyclyl selected from the group comprising morpholinyl, thiomorpholine, 1,1-dioxothiazolidine, piperidine, piperidine-2-it, piperazine-2-it, 8-oxa-3-Aza-bicyclo[3.2.1]octyl, piperazinil and pyrrolidinyl, DG is heterocyclyl optionally substituted hydroxy-lower alkyl or lower alkyl-carbonyl;
R17and R18independently of one another denote hydrogen, lower alkyl, hydroxy-lower alkyl, lower alkoxygroup-lower alkyl; or
NR17R18denotes morpholinyl;
R19and R20independently of one another denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl or lower alkoxygroup-lower alkyl; or
NR19R20means heterocyclyl selected from the group comprising morpholinyl, pyrrolidinyl, 8-oxa-3-Aza-bicyclo[3.2.1]octyl where heterocyclyl optionally substituted by a hydroxy-group, lower alkyl-S(O2);
and their pharmaceutically acceptable salts.

3. Compounds according to claim 1 or 2, where R1denotes phenyl, optionally substituted with halogen, hydroxy-group, hydroxy-lower alkyl or CN.

4. Compounds according to claim 1 or 2, where R1denotes phenyl.

5. Compounds according to claim 1 or 2, where R2denotes hydrogen.

6. Compounds according to claim 1 or 2, where R7does
,,,,
or,
where R11and R12defined in claim 1.

7. Compounds according to claim 1 or 2, where R7does
or,
where R11and R12defined in claim 1.

8. Soy is inane according to claim 1 or 2, where R7does
,
where R11defined in claim 1.

9. Compounds according to claim 1 or 2, where X denotes C(R8R9or NR10where R8, R9and R10defined in claim 1.

10. Compounds according to claim 1 or 2, where R10denotes hydrogen.

11. Compounds according to claim 1 or 2, where R11denotes phenyl or heteroaryl selected from the group including pyridinyl, pyrazinyl, pyridinyl-2-it, indazoles, 1,3-dehydrobenzperidol-2-he, 1,3-dihydroindol-2-it, benzotriazolyl and benzimidazolyl, with phenyl or heteroaryl optionally substituted from 1 to 2 substituents selected from the group comprising lower alkyl, hydroxy-lower alkyl, fluoro-lower alkyl, lower alkoxygroup, halogen, S(O2R13C(O)R14, NO2, NR15R16imidazolyl, pyrazolyl, tetrazolyl, pyrrolyl and phenyl-lower alkoxygroup, imidazolyl optionally substituted lower alkyl, where R13, R14, R15and R16defined in claim 1.

12. Compounds according to claim 1 or 2, where R11denotes phenyl or heteroaryl selected from the group including pyridinyl, pyridinyl-2-it, indazoles, 1,3-dehydrobenzperidol-2-he, 1,3-dihydroindol-2-it, benzotriazolyl and benzimidazolyl, with phenyl or heteroaryl optionally substituted from 1 to 2 substituents selected from the group comprising fluorine-lower al the sludge, halogen, C(O)R14and NR15R16where R14, R15and R16defined in claim 1.

13. Compounds according to claim 1 or 2, where R11denotes a 1H-indazol-5-yl, 1H-indazol-6-yl, 1,3-dihydroindol-2-on-6-yl, 1,3-dehydrobenzperidol-2-he-5-yl, 1,3-dihydroindol-2-he-5-yl, 1H-benzotriazol-5-yl, 1H-benzimidazole-5-yl, 1H-pyridin-2-he-4-yl, 4-forfinal, 3-triptoreline, 1H-benzimidazole-5-yl, 3-benzamid A 5-nicotinamide, 3-(N-ndimethylacetamide)phenyl or 3-(N-methanesulfonamide)phenyl.

14. Compounds according to claim 1 or 2, where R11denotes phenyl or heteroaryl selected from the group comprising 2-oxo-2,3-dihydro-1H-indol-5-yl, pyrimidine-4-one, furanyl, thiadiazolyl, pyrazolyl, isoxazolyl, pyrimidine-2,4-dione, benzoxazin-3-one, 1,4-dihydrobenzoic-2-it, indolyl, thiophenyl, oxazolyl, benzoxazin-2-it, 3,4-dihydroquinazolin-2-it, pyridazinyl, honokalani, benzothiazolyl, benzotriazolyl, naphthyridine, cinnoline, 1,4-dihydroquinoxaline-2,3-dione and 1,2-dihydroindol-3-one, with phenyl or heteroaryl optionally substituted from 1 to 3 substituents selected from the group comprising a hydroxy-group, IN(OH)2, carboxy-lower alkoxygroup, carbarnoyl-lower alkoxygroup, cyano, [1,3,4]oxadiazol-2-it, oxadiazolyl, triazolyl and isoxazolyl where isoxazolyl optionally substituted lower alkyl.

15. Compounds according to claim 1 or 2, where R11denotes phenyl or Goethe is auril, selected from the group including pyridinyl, 1,3-dihydroindol-2-he, 1H-benzimidazolyl, 3H-pyrimidine-4-one, 1H-pyrazolyl, isoxazolyl and 4H-benzo[1,4]oxazin-3-one, with phenyl or heteroaryl optionally substituted from 1 to 3 substituents selected from the group comprising lower alkyl, hydroxy-group, halogen and NR15R16where R14and R15defined in claim 1.

16. Compounds according to claim 1 or 2, where R11refers to 2-methyl-3H-pyrimidine-4-one, 5-methylisoxazol-3-yl, 1H-pyrazole-3-yl, 6-aminopyridine-3-yl, 1,3-dihydroindol-2-it, 2-aminopyridine-4-yl, 4H-benzo[1,4]oxazin-3-one, 1H-benzimidazole-5-yl, 3-(N-ndimethylacetamide)-4-forfinal or 2-hydroxypyridine-4-yl.

17. Compounds according to claim 1 or 2, where R12denotes hydrogen.

18. Compounds according to claim 1 or 2, where R13denotes lower alkyl.

19. Compounds according to claim 1 or 2, where R14denotes NR19R20and where R19and R20defined in claim 1.

20. Compounds according to claim 1 or 2, where R14denotes lower alkyl.

21. Compounds according to claim 1 or 2, where R15and R16independently of one another denote hydrogen, lower alkyl, lower alkyl-carbonyl, lower alkyl-SO2, lower alkenyl-oxycarbonyl or lower alkyl-NH-carbonyl; or NR15R16means heterocyclyl selected from the group comprising morpholinyl, thiomorpholine, 1,1-dioxothiazolidine, piperidine, piperidine-2-it, peep the Razin-2-it, piperazinil and pyrrolidinyl, while heterocyclyl optionally substituted hydroxy-lower alkyl or lower alkyl-carbonyl.

22. Compounds according to claim 1 or 2, where R15and R16independently from each other denote hydrogen, a lower alkyl-carbonyl or lower alkyl-SO2.

23. Compounds according to claim 1 or 2, where NR15R16means heterocyclyl selected from the group comprising 1,1-dioxothiazolidine, pyrrolidin-2-it, imidazolidin-2,4-dione, 2,4-dihydro[1,2,4]triazole-3-one, pyrrolidin-2,5-dione, azetidin-2-he and 1,3-dihydroimidazole-2-it, with heterocyclyl optionally substituted hydroxy-lower alkyl or lower alkyl-carbonyl.

24. Compounds according to claim 1 or 2, where R17and R18independently of one another denote hydrogen or lower alkyl; or NR17R18denotes morpholinyl.

25. Compounds according to claim 1 or 2, where R19and R20independently of one another denote hydrogen, lower alkyl, cycloalkyl, hydroxy-lower alkyl, lower alkoxygroup-lower alkyl; or NR19R20means heterocyclyl selected from the group comprising morpholinyl or pyrrolidinyl, while heterocyclyl optionally substituted hydroxy-group or lower alkyl-S(O2).

26. Compounds according to claim 1 or 2, where R19and R20denote hydrogen.

27. Compounds according to claim 1 or 2, where R19and R20indicate what iano-lower alkyl; or NR19R20means heterocyclyl selected from the group comprising piperidinyl, piperazinil, piperazine-2-it, diazolidinyl, thiomorpholine, 1,3,8-triaza-Spiro[4,5]decane-2,4-dione and Spiro(1-phthalan)piperidine-4-yl, with heterocyclyl optionally substituted by a hydroxy-group, the lower alkyl-(SO2), lower alkyl, lower alkyl-carbonyl, carboxyl group, carbamoyl, lower alkoxy-carbonyl, cyano, phenyl or lower alkoxygroup.

28. Compounds according to claim 1 or 2, which are the R-isomers and which are represented by formula (Ia)
,
where R1, R2, R3, R4, R5, R6, R7and X is defined in one of claims 1 to 27.

29. Compounds according to claim 1 or 2, selected from the group including:
(R)-1-{2-[3-(4-Methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-3-(2-{2-[3-(4-Methoxyphenyl)[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-oksidoksi)benzonitrile,
(R)-1-{2-[3-(4-Methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxypropan-1-he,
(R)-1-{2-[3-(4-Bromophenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-2-(4-Hydroxyphenoxy)-1-{2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-2-(4-Chlorophenoxy)-1-{2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-2-(4-Hydroxymethylene)-1-{2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}this is non,
(R)-2-(3-Chlorophenoxy)-1-{2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-2-(4-Pertenece)-1-{2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-1-{2-[3-(4-Forfinal)-[1,2,4]oxadiazol-5-reparacin-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Methanesulfonyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
(R)-2-(4-Pertenece)-1-[2-(pyridin-4-yl-[1,2,4]oxadiazol-5-yl)piperidine-1-yl]alanon,
Methyl ester of (R)-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
(R)-1-{2-[3-(3-Nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(3-Nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
(R)-2-Phenoxy-1-[2-(3-pyrazin-2-yl-[1,2,4]oxadiazol-5-yl)piperidine-1-yl]alanon,
(R)-1-(2-{3-[4-(Morpholine-4-sulfonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-1-{2-[3-(6-Methoxypyridine-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(3-Hydroxymethylene)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
Allyl ether (R)-6-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinic acid,
(R)-1-{2-[3-(4-Imidazol-1-ylphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-N-Methyl-4-{5-[1-(2-what toxicity)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl)benzosulfimide,
(R)-1-{2-[3-(6-Morpholine-4-espiridion-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-2-Phenoxy-1-{2-[3-(4-triftormetilfullerenov)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-2-Phenoxy-1-{2-[3-(4-triptoreline)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-1-{2-[3-(4-Chlorophenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-N-(4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-2-triptoreline)ndimethylacetamide,
(R)-1-{2-[3-(3-Methanesulfonyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Methyl-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Methoxy-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-N-(2-Hydroxyethyl)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
(R)-N-(2-Methoxyethyl)-N-methyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
(R)-N,N-Dimethyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
(R)-N,N-Diethyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
(R)-1-{2-[3-(2-Morpholine-4-espiridion-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-2-Phenoxy-1-{2-[3-(3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-4'-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-2-Phenoxy-1-{2-[3-(2-thiomorpholine-4-espiridion-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}etano is,
(R)-1-{2-[3-(2-Diethylaminomethyl-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
Ethyl ester of (R)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
(R)-1-(2-{3-[6-(4-Acetylpiperidine-1-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-1-{2-[3-(2-Imidazol-1-espiridion-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)piperidine-2-it,
(R)-1-(2-{3-[4-(3H-Imidazol-4-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-1-(2-{3-[4-(2-Mei-1-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-2-Phenoxy-1-{2-[3-(2-pyrazole-1-espiridion-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
(R)-4-(5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-yl)piperazine-2-it,
(R)-2-Phenoxy-1-(2-{3-[4-(1H-tetrazol-5-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)Etalon,
(R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(1H-Indazol-6-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Fluoro-3-triptoreline)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-6-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydroindol-2-it,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dehydrobenzperidol-2-it,
(R)-5-{5-[1-(2-Phenoxyacetyl)p is piridin-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydroindol-2-it,
(R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-(2-{3-[6-(1,1-Diocletianopolis-4-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-N-(4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-yl)acetamide", she
(R)-1-{2-[3-(6-Benzyloxypyridine-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
Ethyl ester of (R)-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinic acid,
(R)-4-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridine-2-it,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridine-2-it,
(R)-2-Phenoxy-1-[2-(5 phenyl-2H-[1,2,4]triazole-3-yl)piperidine-1-yl]alanon,
(R)-1-{2-[5-(4-Methanesulfonyl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[5-(3,4-Acid)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[5-(3,4-Dichlorophenyl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2 Phenoxyethanol,
(R)-1-{2-[5-(4-Forfinal)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-2-Phenoxy-1-{2-[5-(3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}Etalon,
(R)-1-{2-[5-(4-Methoxyphenyl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[5-(3-Nitrophenyl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
Methyl ester of (R)-3-{5-[1-(2-phenoxyacetyl)Pipa is one-2-yl]-1H-[1,2,4]triazole-3-yl}benzoic acid,
(R)-1-{2-[5-(4-Fluoro-3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-6-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-1,3-dihydroindol-2-it,
1-{3-[3-(4-Methoxyphenyl)-[1,2,4]oxadiazol-5-yl]morpholine-4-yl}-2-phenoxyethane,
1-{3-[3-(4-Methanesulfonyl)-[1,2,4]oxadiazol-5-yl]morpholine-4-yl}-2-phenoxyethane,
4-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
1-(3-{3-[6-(1,1-Diocletianopolis-4-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}morpholine-4-yl)-2-phenoxyethane,
N-(4-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl)pyridine-2-yl)acetamide", she
1-{3-[5-(4-Methanesulfonyl)-2H-[1,2,4]triazole-3-yl]morpholine-4-yl)-2-phenoxyethane,
2 Phenoxy-1-{3-[5-(3-triptoreline)-2H-[1,2,4]triazole-3-yl]morpholine-4-yl}Etalon,
(R)-4-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridine-2-it,
1-{3-[3-(4-Methoxyphenyl)-[1,2,4]oxadiazol-5-yl]thiomorpholine-4-yl}-2-phenoxyethane,
1-{3-[3-(4-Methanesulfonyl)-[1,2,4]oxadiazol-5-yl]thiomorpholine-4-yl}-2-phenoxyethane,
4-{5-[4-(2-Phenoxyacetyl)thiomorpholine-3-yl]-[1,2,4]oxadiazol-3-yl} benzosulfimide,
2 Phenoxy-1-[3-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)thiomorpholine-4-yl]alanon,
1-{2-[3-(4-Methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
N-(5-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl)pyridine-2-yl)acetamide", she
1-{2-[3-(2-Imidazol-1-espiridion-4-yl)-[1,2,4]oxadiazol-5-and the]piperazine-1-yl}-2-phenoxyethane,
N,N-Diethyl-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
N,N-Dimethyl-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
4-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
1-{2-[3-(4-Methanesulfonyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)piperazine-1-yl]alanon,
1-{2-[3-(2,4-Dichlorophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[2-(3-pyridin-2-yl-[1,2,4]oxadiazol-5-yl)piperazine-1-yl]alanon,
2 Phenoxy-1-[2-(3-pyridin-2-yl-[1,2,4]oxadiazol-5-yl)piperazine-2-yl]alanon,
1-{2-[3-(4-Nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[3-(6-Methoxypyridine-3-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[3-(6-Morpholine-4-espiridion-3-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[3-(3-Hydroxymethylene)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[3-(4-Diethylaminophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-(2-{3-[4-(Morpholine-4-sulfonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
N-Methyl-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
N-(2-Methoxyethyl)-N-methyl-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
1-{2-[3-(4-Chlorophenyl)-[1,2,4]oxadiazol-5-and the]piperazine-1-yl}-2-phenoxyethane,
N-(4-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-2-triptoreline)ndimethylacetamide,
Allyl ether of 4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl)benzoic acid
1-{2-[3-(4-Methyl-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[3-(4-Methoxy-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[3-(4-Chloro-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
Methyl ester of 3-fluoro-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
Ethyl ester of 4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}piperidine-2-carboxylic acid,
2 Phenoxy-1-{2-[3-(4-piperidine-1-ylphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}Etalon,
1-{2-[3-(4-(Morpholine-4-ylphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-(2-{3-[4-(2-Mei-1-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
1-(2-{3-[4-(3H-Imidazol-4-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
4-(5-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-yl)piperazine-2-it,
1-{2-[3-(6-Imidazol-1-espiridion-3-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-(2-{3-[6-(4-Acetylpiperidine-1-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
2 Phenoxy-1-{2-[3-(4-pyrrol-1-ylphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}Etalon,
2 Phenoxy-1-{2-[3-(4-triptorelin wltnylfj)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}Etalon,
1-{2-[3-(2-Morpholine-4-espiridion-4-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-{2-[3-(2-thiomorpholine-4-espiridion-4-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}Etalon,
1-(2-{3-[6-(3-Hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl} piperazine-1-yl)-2-phenoxyethane,
(R)-1-{2-[3-(6-Methoxypyridine-3-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(6-Morpholine-4-espiridion-3-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-N-(4-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-2-triptoreline)ndimethylacetamide,
(R)-1-{2-[3-(4-Methyl-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Methyl-3-nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-(Morpholine-4-ylphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-1-(2-{3-[4-(3H-Imidazol-4-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
(R)-1-(2-{3-[6-(3-Hydroxyethylpyrrolidine-1-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
(R)-1-(2-{3-[6-(4-Acetylpiperidine-1-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
Hydrochloride (R)-N-(3-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl} phenyl)acetamide", she
(R)-1-{2-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
Hydrochloride (R)-1-{2-[3-(1H-indazol-5-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dehydrobenzperidol-2-it,
Hydrochloride (R)-1-(2-{3-[6-(1,1-diocletianopolis-4-yl)pyridine-3-yl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
(R)-1-{2-[3-(3-Nitrophenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Forfinal)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-4-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-perigee-2-it,
1-{4-Acetyl-2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
1-{4-Acetyl-2-[3-(4-methanesulfonyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl)-2-phenoxyethane,
4-{5-[4-Acetyl-1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzosulfimide,
1-[4-Acetyl-2-(3-pyridin-4-yl-[1,2,4]oxadiazol-5-yl)piperazine-1-yl]-2-phenoxyethane,
1-{4-Methanesulfonyl-2-[3-(4-methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl} -2-phenoxyethane,
(R)-1-{2-[5-(4-Forfinal)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-2-Phenoxy-1-{2-[5-(3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}Etalon,
1-{2-[5-(4-Fluoro-3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[5-(4-Methanesulfonyl)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-{2-[5-(3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperazine-yl}Etalon,
2 Phenoxy-1-[2-(5-p-tolyl-2H-[1,2,4]triazole-3-yl)piperazine-1-yl]alanon,
2 Phenoxy-1-{2-[5-(4-triptoreline)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}Etalon,
1-{2-[5-(4-Methoxyphenyl)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[5-(4-Forfinal)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[5-(3,4-Acid)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[5-(3,4-Dichlorophenyl)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
1-{2-[5-(2-Forfinal)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl}-2-phenoxyethane,
4-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]-4-methylpiperazin-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-Forfinal)-[1,2,4]oxadiazol-5-yl]-4-methylpiperazin-1-yl}-2-phenoxyethane,
(R)-5-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydroindol-2-it,
(R)-5-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dehydrobenzperidol-2-it,
(R)-1-{2-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]-4-methylpiperazin-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]-4-methylpiperazin-1-yl}-2-phenoxyethane,
(R)-1-{4-Methyl-2-[5-(3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperazine-1-yl)-2-phenoxyethane,
(R)-1-{2-[5-(4-Methoxyphenyl)-2H-[1,2,4]triazole-3-yl]-4-methylpiperazin-1-yl}-2-phenoxyethane,
(R)-1-{2-[5-(4-Forfinal)-2H-[1,2,4]triazole-3-yl]-4-methylpiperid the Jn-1-yl}-2-phenoxyethane,
(R)-1-{2-[5-(4-Methanesulfonyl)-2H-[1,2,4]triazole-3-yl]-4-methylpiperazin-1-yl}-2-phenoxyethane,
Methyl ester of (R)-4-{5-[4-methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoic acid,
(R)-N-(3-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)acetamide", she
(R)-N-(3-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)methanesulfonamide,
(R)-4-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-1H-[1,2,4]triazole-3-yl}benzamide,
(R)-4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
(R)-6-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinic acid,
(R)-2-Fluoro-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
(R)-4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoic acid,
3-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
3-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
4-{5-[4-(2-Phenoxyacetyl)thiomorpholine-3-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
4-{5-[4-(2-Phenoxyacetyl)thiomorpholine-3-yl]-[1,2,4]oxadiazol-4-yl}benzamide,
3-{5-[-Acetyl-1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
4-{5-[4-Acetyl-1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzoic acid,
(R)-4-{5-[4-Methyl-1-(2-phenoxyacetyl)piperazine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoic acid,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinic acid,
1-(2-{3-[4-(Morpholine-4-carbonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-1-(2-{3-[4-(3-Hydroxypyrrolidine-1-carbonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-N,N-Diethyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Methyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N,N-Dimethyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Ethyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Cyclopropyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-(2-Hydroxyethyl)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-(2-Methoxyethyl)-N-methyl-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Methyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N,N-Dimethyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Ethyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Cyclopropyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}ansamed,
(R)-N-(2-Hydroxyethyl)-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-R-(2-Methoxyethyl)-N-methyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-1-(2-{3-[3-(Morpholine-4-carbonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-1-(2-{3-[3-(3-Hydroxypyrrolidine-1-carbonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-N,N-Diethyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
Methylamide (R)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl)pyridine-2-carboxylic acid,
Dimethylamide (R)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
Ethylamide (R)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
Diethylamide (R)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
(R)-1-(2-{3-[2-(Morpholine-4-carbonyl)pyridine-4-yl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
(R)-1-(2-{3-[2-(3-Methanesulfonamido-1-carbonyl)pyridin-4-yl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
Methylamide (R)-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl)pyridine-2-carboxylic acid,
(R)-N-Methyl-3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzamide,
1-N,N-Diethyl-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
1-(2-{3-[4-(is orfelin-4-carbonyl)phenyl]-[1,2,4]oxadiazol-5-yl}piperazine-1-yl)-2-phenoxyethane,
N-Methyl-4-{5-[1-(2-phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-N-Methyl-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-N-Ethyl-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-N-Diethyl-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl)nicotinamide,
(R)-N-Diethyl-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-N-(2-Hydroxyethyl)-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-N-(2-Methoxyethyl)-N-methyl-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-N-Cyclopropyl-5-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-1-(2-{3-[5-(3-Hydroxypyrrolidine-1-carbonyl)pyridin-3-yl]-[1,2,4]oxadiazol-5-yl)piperidine-1-yl)-2-phenoxyethane,
(R)-4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
Amide (R)-4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-carboxylic acid,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzamide,
4-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
4-{5-[4-(2-Phenoxyacetyl)thiomorpholine-3-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
4-{5-[1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl)benzamid,
5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl][1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-1-{2-[3-(3-AMINOPHENYL)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(4-AMINOPHENYL)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[5-(3-AMINOPHENYL)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-N-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)acetamide", she
(R)-N-(4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)acetamide", she
(R)-N-(5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}pyridine-2-yl)acetamide", she
(R)-N-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)acetamide", she
(R)-N-(3-{5-[1-(2-Phenoxyethyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)methanesulfonamide,
(R)-N-(4-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)methanesulfonamide,
Allyl ether (R)-(3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)carbamino acid,
Allyl ether (R)-(4-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)carbamino acid,
(R)-N-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)methanesulfonamide,
(R)-1-Ethyl-3-(3-{5-[1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)urea,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzonitrile, and
(R)-5-(5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
and their pharmaceutically acceptable salts.

30. Compounds according to claim 1 or 2, selected from the group is s, including:
(R)-1-{2-[3-(1H-Indazol-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(1H-Indazol-6-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-6-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydroindol-2-it,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dehydrobenzperidol-2-it,
(R)-5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydroindol-2-it,
(R)-1-{2-[3-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-1-{2-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-4-{5-[4-(2-Phenoxyacetyl)morpholine-3-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridine-2-it,
(R)-1-{2-[5-(4-Forfinal)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
(R)-2-Phenoxy-1-{2-[5-(3-triptoreline)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}Etalon,
(R)-1-{2-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(R)-3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}benzamide,
5-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}nicotinamide,
(R)-N-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)acetamide", she and
(R)-N-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)methanesulfonamide,
and their pharmaceutically acceptable salts.

31. Compounds according to claim 1 or 2, selected from the group including:
1-{(R)-2-[3-(2-Methyl-1H-benzimidazo is l-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[3-(2-Aminopyridine-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[3-(3-Hydroxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
4-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyridine-2-it,
1-{(R)-2-[3-(4-Hydroxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenylboronic acid,
4-(2-Oxo-2-{(R)-2-[3-(2-oxo-2,3-digitron-indol-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}ethoxy)benzonitrile,
4-(2-{(R)-2-[3-(4-Methoxyphenyl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-oksidoksi)benzonitrile,
2-Methyl-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-3H-pyrimidine-4-one,
1-[(R)-2-(3-Furan-2-yl-[1,2,4]oxadiazol-5-yl)piperidine-1-yl]-2-phenoxyethane,
1-[(R)-2-(3-Imidazo[1,2-a]pyridine-2-yl-[1,2,4]oxadiazol-5-yl)piperidine-1-yl]-2-phenoxyethane,
1-{(R)-2-[3-(4-Methyl-[1,2,3]thiadiazole-5-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[3-(2,5-Dimethyl-2H-pyrazole-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-{(R)-2-[3-(1H-pyrazole-4-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
1-{(R)-2-[3-(5-Methylisoxazol-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl)-2-phenoxyethane,
2 Phenoxy-1-{(R)-2-[3-(1H-pyrazole-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}Etalon,
5-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1H-pyrimidine-2,4-dione,
1-{(R)-2-[3-(6-Aminoe the one-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
1-[(R)-2-(3-Imidazo[1,2-a]pyridine-6-yl-[1,2,4]oxadiazol-5-yl)piperidine-1-yl]-2-phenoxyethane,
6-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-4H-benzo[1,4]oxazin-3-one,
6-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,4-dihydrobenzo[d][1,3]oxazin-2-it,
1-((R)-2-{3-[3-(1,1-Dioxo-1λ-6-isothiazolin-2-yl)phenyl]-[1,2,4]oxadiazol-5-yl}piperidine-1-yl)-2-phenoxyethane,
1-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)pyrrolidin-2-it,
1-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)imidazolidin-2,4-dione,
4-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)-2,4-dihydro[1,2,4]triazole-3-one,
1-(3-Fluoro-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)pyrrolidin-2,5-dione,
5-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-1,3-dihydroindol-2-it,
1-{(R)-2-[5-(1H-Indazol-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(1H-Indol-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(3H-Benzotriazol-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
5-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-1,3-dehydrobenzperidol-2-it,
1-{(R)-2-[5-(2-Methyl-1H-benzimidazole-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(2-Aminopyridine-4-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
5-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-N-[1,2,4]triazole-3-yl}phenyl)-3H-[1,3,4]oxadiazol-2-it,
1-{(R)-2-[5-(3-[1,3,4]Oxadiazol-2-ylphenyl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenylboronic acid,
6-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-4H-benzo[1,4]oxazin-3-one,
1-[(N)-2-(5-Imidazo[1,2-a]pyridine-6-yl-2H-[1,2,4]triazole-3-yl)piperidine-1-yl]-2-phenoxyethane,
1-{(N)-2-[5-(6-Aminopyridine-3-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(N)-2-[5-(1H-Benzimidazole-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[(R)-2-(5-pyridin-3-yl-2H-[1,2,4]triazole-3-yl)piperidine-1-yl]alanon,
1-{(R)-2-[5-(3,5-Dimethylisoxazol-4-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[(R)-2-(5-thiophene-2-yl-2H-[1,2,4]triazole-3-yl)piperidine-1-yl]alanon,
2 Phenoxy-1-[(R)-2-(5-pyrimidine-2-yl-2H-[1,2,4]triazole-3-yl)piperidine-1-yl]alanon,
1-{(R)-2-[5-(4-Methoxazole-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[(R)-2-(5-pyrazin-2-yl-2H-[1,2,4]triazole-3-yl)piperidine-1-yl]alanon,
1-{(R)-2-[5-(2-Forfinal)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(3,5-Differenl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(2-Methylpyridin-4-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(3-Forfinal)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(3,4-Differenl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
6-{5-[(R)-1-(2-f is oxyacetic)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-1,4-dihydrobenzo[d][1,3]oxazin-2-it,
7-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-3,4-dihydro-1H-hinzelin-2-it,
1-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)imidazolidin-2,4-dione,
1-{(R)-3-[3-(2-Aminopyridine-4-yl)-[1,2,4]oxadiazol-5-yl]morpholine-4-yl}-2-phenoxyethane,
1-{(R)-3-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]morpholine-4-yl}-2-phenoxyethane,
1-{(R)-2-[3-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
5-{5-[(R)-1-(2-Phenoxyacetyl)piperazine-2-yl]-[1,2,4]oxadiazol-3-yl}-1,3-dihydroindol-2-it,
1-{(R)-2-[3-(2-Aminopyridine-4-yl)-[1,2,4]oxadiazol-5-yl]piperazine-1-yl}-2-phenoxyethane,
(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenoxy)acetic acid,
2 Phenoxy-1-((R)-2-{5-[3-(piperidine-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)Etalon,
1-((R)-2-{5-[3-(Morpholine-4-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
1-((R)-2-{5-[3-(4-Methylpiperazin-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
4-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoyl)piperazine-2-it,
N-(2-Methoxyethyl)-N-methyl-3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl)benzamid,
1-((R)-2-{5-[3-(4-Acetylpiperidine-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
1-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoyl)piperidine-4-carboxylic acid,
Amide 1-(3-{5-[(R)-1-(phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoyl)piperidine-4-carboxylic acid,
2 Phenoxy-1-((R)-2-{5-[3-(thiazolidin-3-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl} piperidine-1-yl)Etalon,
N-(2-Dimethylaminoethyl)-N-methyl-3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzamide,
2 Phenoxy-1-((R)-2-{5-[3-(thiomorpholine-4-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)Etalon,
Ethyl ester of 4-(3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzoyl)piperazine-1-carboxylic acid,
N-(2-Hydroxyethyl)-3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzamide,
N-Methyl-3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-N-(2-pyridin-2-retil)benzamid,
N-(2-Cyanoethyl)-N-cyclopropyl-3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}benzamide,
1-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl)benzoyl)-4-phenylpiperidine-4-carbonitrile,
1-((R)-2-{5-[3-(4-Hydroxypiperidine-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
8-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-benzoyl)-1,3,8-triaza-Spiro[4.5]decane-2,4-dione,
1-(2-{5-[3-(Spiro(1-phthalan)piperidine-4-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
2 Phenoxy-1-((R)-2-{5-[3-(3-pyridin-4-iparralde-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)Etalon,
1-((R)-2-{5-[3-(3-Methane sulfanilamide-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
1-((R)-2-{5-[3-((S)-3-Ethoxypyrrolidine-1-carbon is l)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
1-((R)-2-{5-[3-((8)-3-Hydroxypyrrolidine-1-carbonyl)phenyl]-2H-[1,2,4]triazole-3-yl}piperidine-1-yl)-2-phenoxyethane,
5-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl} nicotinamide,
2-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenoxy)ndimethylacetamide,
N-(3-Fluoro-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)acetamide", she
N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}phenyl)acetamide", she
N-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)propionamide,
N-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)isobutyramide,
N-(4-Fluoro-3-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl)phenyl)acetamide", she
N-(3-Fluoro-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)acetamide", she
N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)acetamide", she
N-(4-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}pyridine-2-yl)acetamide", she
1-(3-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)azetidin-2-it,
1-(3-{5-[1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)pyrrolidin-2,5-dione,
2 Phenoxy-1-[(R)-2-(5-pyridazin-4-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]alanon,
4-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}benzonitrile,
1-{(R)-2-[5-(3-Aminopyridin-2-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
3-{3-[(R)-1-(2-Venoxis the Teal)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}benzonitrile,
1-{(R)-2-[5-(2-Hydroxypyridine-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(5-Aminopyridine-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl)-2-phenoxyethane,
1-{(R)-2-[5-(2-Hydroxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl)-2-phenoxyethane,
1-{(R)-2-[5-(2-Hydroxy-6-methylpyridin-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(4-Hydroxypyridine-2-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(2-Amino-5-chloropyrimidine-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[(R)-2-(5-pyrazin-2-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]alanon,
2 Phenoxy-1-{(R)-2-[5-(4-[1,2,4]triazole-1-ylphenyl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}Etalon,
2 Phenoxy-1-{(R)-2-[5-(4-tetrazol-1-ylphenyl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}Etalon,
1-{(R)-2-[5-(1H-Benzimidazole-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl)-2-phenoxyethane,
1-{(R)-2-[5-(4-Acetylphenyl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(6-Hydroxypyridine-2-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(5-Methylpyrazine-2-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-[(R)-2-(5-cinoxacin-2-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]alanon,
1-{(R)-2-[5-(3-Methanesulfonyl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(6-Chloropyridin-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-[(R)-2-(5-Benzothiazol-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]-2-phenoxyethane,
2 Phenoxy-1-{(R)-2-[5-(2,4,5-tryptophanyl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}Etalon,
2 Phenoxy-1-{(R)-2-[5-(6-triptorelin-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}Etalon,
1-[(R)-2-(5-Benzo[1,2,3]thiadiazole-5-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]-2-phenoxyethane,
1-[(R)-2-(5-[1,8]Naphthiridine-2-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]-2-phenoxyethane,
1-[(R)-2-(5-[1,6]Naphthiridine-2-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]-2-phenoxyethane,
1-[(R)-2-(5-Cinnolin-4-yl-[1,2,4]oxadiazol-3-yl)piperidine-1-yl]-2-phenoxyethane,
1-{(R)-2-[5-(1H-Benzotriazol-5-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(1H-Benzimidazole-5-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(3,6-Dichloropyridazin-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
6-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}-4H-benzo[1,4]oxazin-3-one,
1-{(R)-2-[5-(3H-Imidazo[4,5-b]pyridine-6-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
N-(4-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}pyridine-2-yl)acetamide", she
1-{(R)-2-[5-(6-Chloro-3-hydroxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
6-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}-1,4-dihydroquinoxaline-2,3-dione,
1-{(R)-2-[5-(6-Hydroxypyridine-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
7-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}-3,4-dihydro-1H-chinox the Lin-2-it,
1-{(R)-2-[5-(6-Aminopyridine-2-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
6-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}nicotinamide,
5-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}pyridine-2-carbonitrile,
4-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}-1,2-dihydropyrazol-3-one,
1-{(R)-2-[5-(2-Aminopyridine-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(6-Hydroxypyrimidine-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
4-(3-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}phenyl)-2,4-dihydro[1,2,4]triazole-3-one,
1-(3-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}phenyl)imidazolidin-2,4-dione,
1-((R)-2-{5-[3-(1,1-Dioxo-1λ,6-isothiazolin-2-yl)phenyl]-[1,2,4]oxadiazol-3-yl}piperidine-1-yl)-2-phenoxyethane,
1-(3-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl)phenyl)pyrrolidin-2-it,
1-(3-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}phenyl)-1,3-dihydroimidazole-2-it,
3-(3-{3-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-5-yl}phenyl)imidazolidin-2,4-dione,
1-{(R)-2-[5-(1-Methyl-1H-pyrazole-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-{(R)-2-[5-(1H-pyrazole-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}Etalon,
1-{(R)-2-[5-(5-Methylisoxazol-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl} -2-phenoxyethane,
1-{(R)-2-[5-(2,5-Dimethyl-2H-pyrazole-3-yl)-[1,2,4]oxadi the evil-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(5-Methyl-2H-pyrazole-3-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane, and
1-{(R)-2-[5-(3-Methylisoxazol-5-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl}-2-phenoxyethane,
and their pharmaceutically acceptable salts.

32. Compounds according to claim 1 or 2, selected from the group including:
2-Methyl-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-[1,2,4]oxadiazol-3-yl}-3H-pyrimidine-4-one,
1-{(R)-2-[3-(5-Methylisoxazol-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
2 Phenoxy-1-{(R)-2-[3-(1H-pyrazole-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl)Etalon,
1-{(R)-2-[3-(6-Aminopyridine-3-yl)-[1,2,4]oxadiazol-5-yl]piperidine-1-yl}-2-phenoxyethane,
5-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-1,3-dihydroindol-2-it,
1-{(R)-2-[5-(2-Aminopyridine-4-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
6-{5-[(R)-1-(2-Phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}-4H-benzo[1,4]oxazin-3-one,
1-{(R)-2-[5-(6-Aminopyridine-3-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
1-{(R)-2-[5-(1H-Benzimidazole-5-yl)-2H-[1,2,4]triazole-3-yl]piperidine-1-yl}-2-phenoxyethane,
N-(2-Fluoro-5-{5-[(R)-1-(2-phenoxyacetyl)piperidine-2-yl]-1H-[1,2,4]triazole-3-yl}phenyl)acetamide", she and
1-{(R)-2-[5-(2-Hydroxypyridine-4-yl)-[1,2,4]oxadiazol-3-yl]piperidine-1-yl)-2-phenoxyethane,
and their pharmaceutically acceptable salts.

33. Compounds according to claim 1 or 2, intended for use as therapeutically active substances for the treatment and/or prevention of hyperglycemia, tolerant to glucose disorders, diabetes and associated pathologies, non-insulin dependent diabetes mellitus, obesity, hypertension, syndrome of insulin resistance, metabolic syndrome, hyperlipidemia, hypercholesterolemia, fatty liver, atherosclerosis, congestive heart failure and renal failure.

34. Compounds according to claim 1 or 2, intended for use as therapeutically active substances for the treatment and/or prophylaxis of diseases modulated L-CPT1 inhibitors.

35. Pharmaceutical composition for treatment and/or prevention of hyperglycemia, tolerant to glucose disorders, diabetes and associated pathologies, non-insulin dependent diabetes mellitus, obesity, hypertension, syndrome of insulin resistance, metabolic syndrome, hyperlipidemia, hypercholesterolemia, fatty liver, atherosclerosis, congestive heart failure and kidney failure, including a connection according to one of claims 1 to 32, and a pharmaceutically acceptable carrier and/or excipient.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to a novel salt form of 5-[(2R,5S)-5-methyl-4-propylmorpholin-2-yl]piridine-2-amine (I): , and specifically to 5-[2R,5S)-5-methyl-4-propylmorpholin-2-yl]pyridine-2-amine di-(1S)-camphorsulphonate (di-S-camsylate), to a pharmaceutical composition having effect on dopamine D3 receptor, as well use of the given compound in preparing a medicinal agent for treating sexual dysfunction and neuropsychiatric disorders and a method of obtaining the said compound and an intermediate compound.

EFFECT: novel salt form of a dopamine agonist which has advantages, specifically is not hygroscopic, has a crystalline form and has high melting point is obtained and described.

11 cl, 9 ex, 2 tbl, 6 dwg

FIELD: chemistry.

SUBSTANCE: benzamide derivatives are presented by the formula [1] or its salt, where Z is -O-, -NR5-, -S-, -SO-; 1 is 0 or 1; m is 0 or 1; R1 is hydrogen atom, C1-6-alkyl group, R2 is hydrogen atom, hydroxylic group, C1-6- alkyl group, carboxyl group, C1-6-alkoxycarbonyl group or -CONR10R11, or R2 and R1 together form =O; R3 is hydrogen atom or C1-6-alkyl group; R4 is hydrogen atom or halogen atom; V is direct bond or -(CR21R22)n-; P1 and P2 rings are the same or different, and each is aromatic or saturated carbocyclic group, or 5-10-member saturated or unsaturated heterocyclic group containing 1-3 heteroatoms selected out of N, O, S.

EFFECT: obtainment of compound with excellent inhibition effect on vanilloid receptor type 1 activity, efficiency in treatment of diseases involving vanilloid receptor type 1 activity.

17 cl, 56 tbl, 8 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to phenylalanine derivatives and their pharmaceutically acceptable salts. In formula (1) R11 is a hydroxyl group, an alkoxyl group having 1-6 carbon atoms, which can be substituted with a methoxy group, cycloalkoxyl group having 3-6 carbon atoms, or a benzyloxy group; R12 and R13 each independently represents a hydrogen atom, alkyl group having 1-6 carbon atoms, cycloalkyl group having 3-6 carbon atoms, acetyl group or methyloxycarbonyl group, or N(R12)R13 is a 1-pyrrolidinyl group, 1-piperidinyl group, 4-morpholinyl group; R14 is a methyl group; R1' is a hydrogen atom, fluorine atom; X1 is -CH(R1a)-, -CH(R1a)CH(R1b)-, -CH(R1a)CH(R1b)CH(R1c)-, -N(R1a)CH(R1b)CH(R1c)-, -OCH(R1a)CH(R1b)-, -OCH(R1a)CH(R1b)CH(R1c)- or 1,3-pyrrolidinylene, where R1a, R1b, each independently represents a hydrogen atom or a methyl group, and R1c is a hydrogen atom; Y11 and Y12 represent any of the combinations (CI, Cl), (CI, Me), (CI, F). Invention also relates to phenylalanine derivatives of formulae (2)-(14), given in the formula of invention.

EFFECT: obtaining a pharmaceutical composition having antagonistic effect on α4-integrin, containing a phenylalanine derivative as an active ingredient, a α4-integrin antagonist and a therapeutic agent.

65 cl, 51 tbl, 244 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula

,

where the carbon atom denoted * is in R- or S-configuration; X is a concentrated bicyclic carbocycle or heterocycle selected from a group consisting of benzofuranyl, benzo[b]thiophenyl, benzoisothiazolyl, indazolyl, indolyl, benzooxazolyl, benzothiazolyl, indenyl, indanyl, dihydrobenzocycloheptenyl, naphthyl, tetrahydronaphthyl, quinolinyl, isoquinolinyl, quinoxalinyl, 2H-chromenyl, imidazo[1.2-a]pyridinyl, pyrazolo[1.5-a]pyridinyl, and condensed bicyclic carbocycle or condensed bicyclic heterocycle, optionally substituted with substitutes (1 to 4) which are defined below for R14; R1 is H, C1-C6-alkyl, C3-C6-cyclalkyl, C1-C3-alkyl, substituted OR11, -NR9R10 or -CN; R2 is H, C1-C6-alkyl, or gem-dimethyl; R3 is H, -OR11, C1-C6-alkyl or halogen; R4 is H, halogen, -OR11, -CN, C1-C6-alkyl, C1-C6-alkyl, substituted -NR9R10, C3-C6-cycloalkyl, substituted -NR9R10, C(O)R12; or R4 is morpholinyl, piperidinyl, pyrimidinyl, pyridazinyl, pyrazinyl, pyrrolyl, isoxazolyl, pyrrolidinyl, piperazinyl, 2-oxo-2H-pyridinyl, [1.2.4]triazolo[4.3-a]pyridinyl, 3-oxo-[1.2.4]triazolo[4.3-a]pyridinyl, quinoxalinyl, which are optionally substituted with substitutes (1 to 4) which are defined below for R14; R5 is H or C1-C6-alkyl; R6 is H, C1-C6-alkyl, or -OR11; R7 is H; R8 is H, -OR9, C1-C6-alkyl, -CN; R9 is H or C1-C4-alkyl; R10 is H or C1-C4-alkyl; or R9 and R10 taken together with the nitrogen atom to which they are bonded form morpholine; R11 is H, C1-C4-alkyl; R12 is C1-C6-alkyl; R14 in each case is independently selected from a substitute selected from a group consisting of halogen, -OR11, -NR11R12, C1-C6-alkyl, which is optionally substituted with 1-3 substitutes, in each case independently selected from a group consisting of C1-C3-alkyl, aryl; or to pharmaceutically acceptable salts thereof. The invention also relates to a pharmaceutical composition, to a method of obtaining formula (I) compounds, as well as to a method of treating disorders.

EFFECT: obtaining new biological active compounds having norepinephrine, dopamine and serotonin reuptake selective inhibitory activity.

90 cl, 162 ex, 2 tbl

Mif inhibitors // 2383541

FIELD: chemistry.

SUBSTANCE: there is described compound of formula 1

where R1 represents unsubstituted or substituted (C3-C8)cycloalkyl(C1-C4)alkyl, phenyl(C1-C4)alkyl, (C3-C8)cycloalkyl, phenyl, naphthyl, phenyl condensed with 18-(crown)-6, where substitutes include phenyl, halogen, hydroxy, aminosulfonyloxy, (C1-C4)alkoxy, tri(C1-C6)alkylsilyloxy, halogen(C1-C4)alkyl or halogen(C1-C4)alkoxy, R2 represents hydrogen, hydroxyl, aminosulfonyloxy, (C1-C4)alkoxy, tri(C1-C6)alkylsilyloxy or halogen(C1-C4)alkoxy. Also described is use of the compound for making a medicinal agent and a pharmaceutical composition.

EFFECT: disclosed compounds have macrophage migration inhibitory factor activity (MIF).

8 cl, 1 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

where R1 is hydrogen, alkyl, cycloalkyl, hydroxy group, hydroxyalkyl, alkoxy group, alkoxyalkyl, aminoalkyl, aryl, heterocyclyl, alkylsulfonyl, alkylsulfanyl, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, aminocarbonylalkyl, heterocyclylcarbonylalkyl, alkoxycarbonylalkyl, alkoxyalkylaminocarbonylalkyl, cycloalkylalkoxyalkyl, arylalkyloxyalkyl, aryloxyalkyl, haloidalkyl, haloidalkoxy group or haloidalkoxyalkyl, R2 is hydrogen, alkyl, cycloalkylalkoxyalkyl, alkoxyalkyl, arylalkoxyalkyl, haloidalkoxyalkyl, pyrrolidyl, morpholinyl, thiomorpholinyl, arylalkyl, arylalkoxy group, aryloxy group or heterocyclylalkyl, R3 is hydrogen or alkyl, R4 is hydrogen, alkyl or haloid, R5 is phenyl, naphthyl, piperidyl or 1,2,3,4-tetrahydroisoquinolinyl optionally substituted with one or more substitutes independently selected from alkyl, cycloalkyl, haloid, alkoxy group, nitro group, trifluoromethyl, trifluoromethoxy group, trifluoromethylcarbonyl group, aryl, aryloxy group, alkoxycarbonylalkoxy group and alkylsulfonyl, R6 is hydrogen or alkyl, and their pharmaceutically acceptable salts and esters, under the condition that N-(6-(1,1-dimethylethyl)-2-pyridinyl)-4-methylbenzenesulfamide is excluded, and in cases when R1 is hydrogen or methyl, R2 is not hydrogen or methyl, as well as a pharceutical composition based on these compounds.

EFFECT: novel chemical compounds which can be used in treating and preventing diabetes, obesity and eating disorders are obtained and described.

15 cl, 192 ex

FIELD: chemistry.

SUBSTANCE: described are compounds of formula ; or their pharmaceutically acceptable salts, where A is phenyl, X is CH2- or C=O; Y is O; k equals 1; m equals 0; R2 and R3 each independently represents hydrogen or alkyl, R4 is a group of formula or . Disclosed compounds have selective affinity to 5-HT6 and 5-HT2A receptors. Also described is a pharmaceutical composition containing said compounds and use of the said compounds in making a medicinal agent for treating diseased conditions of the central nervous system.

EFFECT: more effective treatment.

49 cl, 1 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a combined product containing compounds of formula (I): where: R1 and R2 represent CF3; R3 and R4 represent fluoro; R5 and R6 represent hydrogen; R7 presents Cl, X represents CR8, where R8 represents Cl; and R9 represents NH2; or its veterinary acceptable salt, and b) doramectin. The invention also relates to an antiparasitic veterinary composition based on the said combined product.

EFFECT: obtaining a combined product which can be used in veterinary for treating parasitic infections in mammals.

4 cl, 1 dwg, 1 tbl, 37 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound of formula (I) or to salts thereof: , where R1 is a hydrogen atom, amino group, R11-NH-, where R11 is a C1-6alkyl group, hydroxy-C1-6alkyl group, C1-6alkoxycarbonyl-C1-6alkyl group, R12-(CO)-NH-, where R12 is a C1-6alkyl group or C1-6alkoxy-C1-6alkyl group, C1-6alkyl group, hydroxy-C1-6-alkyl group, C1-6alkoxy group or C1-6alkoxy-C1-6alkyl group; R2 is a hydrogen atom, C1-6alkyl group, amino group or di-C1-6alkylamino group; one of X and Y represents a nitrogen atom, while the other represents a nitrogen or oxygen atom; ring A is a 5- or 6-member heteroaryl ring or benzene ring which can have 1 or 2 halogen atoms; Z is a single bond, methylene group, ethylene group, oxygen atom, sulphur atom, -CH2O-, -OCH2-, -NH-, -CH2NH-, -NHCH2-, -CH2S- or -SCH2-; R3 is hydrogen or a halogen atom, or C1-6alkyl group, C3-8cycloalkyl group, C6-10aryl group, 5- or 6-member heteroaryl group, where these groups can have 1 or 2 substitutes selected from a group of α substitutes: and [group of α substitutes] group of α substitutes is a group consisting of a halogen atom, cyano group, C1-6alkyl group, C1-6alkoxy group, C1-6alkoxycarbonyl group, C3-8cycloalkyl group, C1-6alkenyl group and C1-6alkynyl group; R4 is a hydrogen atom or halogen atom; except compounds in which all of R1, R2 and R4 represent a hydrogen atom while Z represents a single bond or R3 is a hydrogen atom; as well as a pharmaceutical composition and a medicinal agent with antifungal activity, based on these compounds, to an antifungal agent and use of formula I compounds for preparing an antifungal agent.

EFFECT: novel compounds with excellent antifungal effect are obtained and described.

36 cl, 228 ex, 8 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pharmaceutical industry and concerns a composition for glucose delivery through an oral mucosa for increasing of glucose (sugar) blood level of an individual. The composition contains: a. effective amount of glucose, b. effective amount of sodium glycocholate, c. effective amount of a pharmaceutically acceptable carrier; the composition it is free from additional active pharmaceutical agents.

EFFECT: development of the effective method for increasing glucose (sugar) blood level.

13 cl, 9 ex, 4 tbl, 7 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I) which are protein tyrosine kinase 1B(PTP-1B) inhibitors and can be used in medicinal preparations for treating and preventing diseases related to high concentration of glucose in blood, for example diabetes and obesity. In formula (I) X is a X-1 group or X-2: , where R1 and R2 are each independently selected from a group consisting of hydrogen, lower alkyl, alkoxy-lower alkyl and hydroxyl-lower alkyl, under the condition that, R1 and R2 both represent hydrogen; R3, R4, R6 and R7 are each independently selected from a group consisting of hydrogen, lower alkyl; lower alkyl substituted with halogen or hydroxy; lower alkoxy; lower alkoxy substituted with halogen, hydroxy or lower alkoxy; hydroxyl, halogen, lower alkylthio, lower alkylsufanyl, lower alkylsufanyl, aminosufonyl, cyano, nitro, carbamoyl, lower mono- or dialkylcarbamoyl, lower alkanoyl, benzoyl, phenyl, phenyl substituted with halogen, phenyloxy, lower mono- or dialkylamino, hydroxy-substituted lower alkylamino, lower alkanoylamino, lower alkylsulfonylamino, heterocycloalkyl, hydroxy-substituted heterocycloalkyl, heterocyclyloxy, heterocyclylcarbonyl; where each heterocycloalkyl in the said values represents a 5-6-membr ring containing 1-2 heteroatoms selected from nitrogen and oxygen, and which can be substituted with lower alkyl or phenyl-lower alkyl; carboxyl, lower alkoxycarbonyl and a substitute of formula: ; R8 is selected from a group consisting of hydrogen, lower alkylthio, halogen, alkoxy-lower alkoxy, lower alkoxy, halogen-lower alkyl, hydroxy-lower alkyl; represents a 5-member heteroaromatic ring containing 1 or 2 heteroatoms selected from a group consisting of hydrogen, sulphur and nitrogen; R8 and R9 each independently represents hydrogen or lower alkyl.

EFFECT: novel compounds have useful biological properties.

31 cl, 7 dwg, 152 ex

FIELD: medicine.

SUBSTANCE: present invention concerns new, selectable hybrid polypeptides expressing at least two hormonal activities containing a first biologically active module of a peptide hormone covalently bonded with at least one additional biologically active module of the peptide hormone.

EFFECT: polypeptides can be used as agents for treatment and prevention of metabolic diseases and disorders associated with overweight.

19 cl, 6 dwg, 6 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new 2-alkylsufanyl-3-arylsufonyl-cycloalkano[e]pyrazolol[1,5-a]pyrimidines of general formula 1 or 2-alkylsufanyl-3-arylsufonyl-cycloalkano[d]pyrazolo[1,5-a]pyrimidines of general formula 2, which are antagonist of 5-HT6 receptors. In compounds of formula 1

and 2 ,

R1 is a hydrogen atom or C1-C3 alkyl; R2 is C1-C3 alkyl; R3 is a hydrogen atom, one or two optionally identical halogen atoms, C1-C3 alkyl or hydroxyl, optionally substituted with C1-C3 alkyl; n is an integer equal to 1, 2 or 3.

EFFECT: compounds can be used in preventing and treating diseases of the central nervous system, anxiolytics and as compounds with nootropic effect and suitable for enhancing memory.

12 cl, 1 dwg, 4 tbl, 9 ex

Diabetes treatment // 2363465

FIELD: medicine.

SUBSTANCE: present group of inventions relates to medicine, particularly to endocrinology. For this purpose sufficient amounts of a compound which inhibits HIF hydroxylase activity are introduced.

EFFECT: design of a method of treating diabetes and other conditions, related to glucose pathometabolism, through stabilisation of HIFα.

8 cl, 12 dwg

FIELD: medicine.

SUBSTANCE: invention refers to pharmacology. The method for improving amino acid absorption in a vertebrate, including a mammal and a bird, includes introduction to a vertebrate of AKG (alpha-ketoglutaric acid), mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in amount and/or at rate sufficient to maintain the desired effect. The method for decreasing plasma glucose absorption in a vertebrate, including a mammal and a bird, involves introduction to a vertebrate, including a mammal and a bird, of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in amount and/or at rate sufficient to maintain the desired effect of glucose absorption. The method of prevention, inhibition or relief of the condition with high-glucose plasma level in a vertebrate, including a mammal and a bird includes introduction to a vertebrate, including a mammal and a bird, of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in amount and/or at rate sufficient to maintain the desired effect on the specified condition.

EFFECT: application of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures in therapeutically effective amount for making the composition used to prevent, relieve and treat the condition with high-glucose plasma level, application of AKG, mono- and dimetallic AKG salts, chitosan-AKG or their mixtures for making the composition used to improve absorption, changed absorption, deteriorated absorption and disordered absorption of amino acids and/or peptides.

19 cl, 3 tbl, 3 ex, 1 dwg

FIELD: medicine.

SUBSTANCE: invention claims bioactive agent in the form of compound of formula (I) , where n is 1 or 2, m is 0, q is 0, t is 0, R9 is hydrogen, A is phenyl substituted by 1 or 2 groups selected out of alkyl with 1 or 2 carbon atoms, X is -CH2CR12R13- group where each of R12 and R13 is hydrogen, Q is OR1, R1 is hydrogen or alkyl with 1 to 7 carbon atoms, and agent application in medicine manufacturing for treatment of state selected out of group including resistance syndrome and diabetes.

EFFECT: method of treatment for mammal subject with state selected out of insulin resistance syndrome, diabetes, hyperlipidemia, fatty liver, cachexia, adiposity, atherosclerosis, and arteriosclerosis, involving daily oral administration of 1 to 400 mg of bioactive agent, and pharmaceutical composition based on the bioactive agent.

12 cl, 1 tbl, 2 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to novel derivatives of diaminopyrrolo quinazoline of formula (I), which possess properties of protein tyrosine phosphatase PTP-1B inhibitors and can be used for reduction of glucose concentration in blood. In general formula (I) A stands for 5- or 6-member unsaturated or saturated hydrocarbon ring or 5- or 6-member unsaturated or saturated ring, which contains at least one heteroatom, selected from S, N or O, R1 represents hydrogen or lower alkyl; Ra represents hydrogen,

,

,

,

or lower alkyl , R1, Ra, Rb, Rc, Rd, Re, Rf are such as defined in invention formula.

EFFECT: obtaining derivatives of diaminopyrrolo quinazoline which possess properties of protein tyrosine phosphatase inhibitors.

32 cl, 5 dwg, 118 ex

FIELD: chemistry.

SUBSTANCE: invention concerns biotechnology, specifically production of new polypeptides regulating carbohydrate metabolism, and can be used in medicine. New polypeptides reacting as both GLP-1 receptor agonists and glucagon receptor antagonists. Polypeptides and coding nucleic acids are used as components of pharmaceutical compositions for treatment of diabetes type 2 and metabolism disorders.

EFFECT: production of compounds providing effective glucose homeostasis for patients, suffering from carbohydrate metabolism disorders.

18 cl, 1 dwg, 4 tbl, 20 ex

FIELD: medicine; endocrinology.

SUBSTANCE: invention refers to treatment pancreatic diabetes and related complications. Invention implies that method includes introduction of insulin susceptibility intensifier (excepting throglytasone) combined with one agent of group including inhibitor of aldose reductase, byhuanide, statin compounds, squalen synthesis inhibitor, fibrate compound, low-density lipoprotein (LDL) catabolism intensifier and angiotensin converting enzyme inhibitor.

EFFECT: lowered complication risk.

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and medicine, namely to a new hypolipidemic preparation representing a molecular complex of atorvastatin and β-glycyrrhizic acid at the mole ration of atorvastatin: β-glycyrrhizic acid 1: (1-4).

EFFECT: invention exhibits high efficiency with much smaller dosage than initial atorvastatin.

5 ex, 2 dwg, 3 tbl

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