Aspartate protease inhibitors

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general structural formula:

or to pharmaceutically acceptable salts, where Z denotes -O- or -CH2- or -CH2-CH2-; X1 denotes a covalent bond or -O-; Y1 denotes a covalent bond or C1-C10 alkylene, provided that Y1 is a covalent bond only when X1 denotes a covalent bond; R1 denotes a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which is a monovalent heteroatomatic monocyclic radical ring containing 1-2 heteroatoms, independently selected from nitrogen and sulphur, possibly substituted with 1-3 groups, independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-alkoxy; R2 denotes -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(NHR9) or -NHC(O)H, where R9 denotes a linear or branched C1-C5 alkyl or a linear or branched (C1-C5)alkoxyalkyl; R3 denotes H, C1-C5 alkyl, -NHC(O)R10 or OH, where R10 denotes C1-C3 alkyl, provided that when R3 denotes -OH, X1 is not O and R2-Y1-X1 is not -OC(O)(NH2), -OC(O)(NHR9), -NHC(O)OR9 or -NHC(O)H; -Q denotes

, where N and N are bonded by bonds denoted by a wavy line; R4 denotes H; R5 and R6 independently denote: a) H, (C1-C10)alkyl, (C4-C10)cycloalkylalkyl, hydroxylated (C4-C10)cycloalkylalkyl, halo(C4-C10)cycloalkylalkyl, (C1-C2)alkyl(C4-C10)cycloakylalkyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl, where the saturated heterocyclic ring is selected from 5-, 6- or 7-member heterocyclic rings which contain 1 heteroatom independently selected from N and O; or b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which is possibly with 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that both R5 and R6 are not H; G denotes NH2 or NHR7; R7 denotes (C1-C6)alkyl; or R5 and R7 together denote -CH2, -(CH2)2 or -(CH2)3, possibly substituted with 1-2 groups independently selected from (C1-C8)-alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy. The invention also relates to compounds selected from the group, pharmaceutical compositions, a method for antagonising one or more aspartate proteases, as well as methods of treating aspartate protease-mediated disorders.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

35 cl, 33 ex, 4 dwg

 

The text descriptions are given in facsimile form.

1. The compound of General structural formula:

or its pharmaceutically acceptable salt,
where Z denotes-O - or-CH2- or-CH2-CH2-;
X1denotes a covalent bond or-O-;
Y1denotes a covalent bond or C1-C10alkylene, provided that Y1is a covalent bond only when X1denotes a covalent bond;
R1means (a) (C3-C7)cycloalkyl or b) phenyl or heteroaryl, which represents a monovalent heteroaromatic monocyclic ring radical containing from 1 to 2 heteroatoms independently selected from nitrogen and sulfur, possibly substituted by 1-3 groups independently selected from fluorine, chlorine, bromine, (C1-C6)alkyl or (C1-C6)-is laksi;
R2refers to-OC(O)(NH2), -OC(O)(other9), -NHC(O)OR9, -C(O)R9, -C(O)(NH2), -C(O)(other9or-NHC(O)H, where R9denotes a linear or branched C1-C5alkyl or linear or branched (C1-C5)alkoxyalkyl;
R3denotes H, C1-C5alkyl, -NHC(O)R10or is HE, where R10represents C1-C3alkyl, provided that when R3means is HE, then X1is O and R2-Y1-X1is not-OC(O)(NH2), -OC(O)(other9)-, NHC(O)OR9or-NHC(O)H;
Q represents Q1 or Q4:

where N and N are attached to the relations denoted by a wavy line;
R4denotes H;
R5and R6independently stand for:
a) N, (C1-C10)alkyl, (C4-C10)cycloalkenyl, gidroksilirovanii (C4-C10)cycloalkenyl, halo, (C4-C10)cycloalkenyl, (C1-C2)alkyl(C4-C10)cycloalkenyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl (C1-C3)alkyl, where saturated heterocyclic ring chosen from 5-, 6 - and 7-membered heterocyclic rings which contain 1 heteroatom independently selected from N and O; or
b) phenyl(C1-C2)is lcil, phenoxymethyl, each of which is possibly substituted by 1-3 groups independently selected from fluorine, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy; provided that R5and R6both are not H;
G denotes NH2or other7;
R7means (C1-C6)alkyl; or
R5and R7together represent-CH2, -(CH2)2or -(CH2)3possibly substituted by 1-2 groups independently selected from (C1-C8)alkyl, (C3-C6)cycloalkyl, (C3-C6)cycloalkyl(C1-C2)alkyl or (C1-C8)alkoxy.

2. The compound according to claim 1 represented by the structural formula:

or its pharmaceutically acceptable salt.

3. The compound according to claim 2, wherein one of R5and R6denotes H or methyl and the other represents
a) N, (C1-C10)alkyl, (C4-C10)cycloalkenyl, gidroksilirovanii(C4-C10)cycloalkenyl, halo, (C4-C10)cycloalkenyl, (C1-C2)-alkyl(C4-C10)cycloalkenyl, (C4-C10)bicycloalkyl(C1-C3)-alkyl, (C1-C5)alkoxy(C1-C5)alkyl, or saturated heterocyclyl(C1-C3)alkyl, where a saturated heterocyclic ring selected the 5-, 6 - and 7-membered heterocyclic rings which contain 1 heteroatom independently selected from N and O; or
b) phenyl(C1-C2)alkyl, phenoxymethyl, each of which may be substituted with 1-3 groups independently selected from fluorine, chlorine, or (C1-C3)alkyl, (C1-C3)alkoxy.

4. The compound according to claim 3, wherein R6denotes H or methyl, or R5denotes H or methyl.

5. The compound according to claim 2, represented by a structural formula selected from the group including:

or its pharmaceutically acceptable salt, where R5means:
a) N, (C1-C10)alkyl, (C4-C10)cycloalkenyl, gidroksilirovanii (C4-C10)cycloalkenyl, halo, (C4-C10)cycloalkenyl, (C1-C2)-alkyl(C4-C10)cycloalkenyl, (C4-C10)bicycloalkyl(C1-C3)alkyl, (C1-C5)alkoxy(C1-C5)alkyl; or a saturated heterocyclyl(C1-C3)alkyl; where saturated heterocyclic ring chosen from 5-, 6 - and 7-membered heterocyclic rings which contain 1 heteroatom independently selected from N and O; or
b) phenyl(C1-C2)alkyl or phenoxymethyl, each of which is possibly substituted by 1-3 groups independently selected from the Torah, chlorine, (C1-C3)alkyl, (C1-C3)alkoxy.

6. The compound according to claim 5 represented by the structural formula

or its pharmaceutically acceptable salt,
where R11denotes fluorine, chlorine, bromine, (C1-C6)alkyl, (C1-C6)-alkoxy;
n is 0, 1, 2 or 3 and
m is 2 or 3.

7. The compound according to claim 5, represented by a structural formula selected from the group including:

or its pharmaceutically acceptable salt,
where R11denotes fluorine, chlorine, bromine, (C1-C6)alkyl, (C1-C6)-alkoxy;
n is 0, 1, 2 or 3 and
m is 2 or 3.

8. The connection according to claim 6 or 7, characterized in that
R5means (C1-C7)alkyl, cyclohexylmethyl, galactically, gidroksilirovanii cyclohexylmethyl, 2-(cyclohexyl)methyl, (C1-C2)alkylcyclohexanes, (3-nidamental)methyl or (tetrahydropyranyl)methyl; and
R6denotes H or methyl;
G denotes NH2or other7;
R7denotes methyl, or R5and R7together form -(CH2)3possibly substituted (C1-C4)alkyl or cyclohexyl.

9. The connection of claim 8, represented by the structural formula:

or its pharmaceutically acceptable salt.

10. Connect the tion of claim 8, represented by a structural formula selected from:

or its pharmaceutically acceptable salt.

11. The compound according to claim 1, represented by the following structural formula:

or its pharmaceutically acceptable salt,
where R5denotes H or methyl;
R6denotes H, (C1-C7)alkyl, cyclohexylmethyl, galactically, gidroksilirovanii cyclohexylmethyl, (C1-C2)alkylcyclohexanes, (3-nidamental)-methyl or (tetrahydropyranyl)methyl; and
R11denotes fluorine, chlorine, bromine, (C1-C6)alkyl, (C1-C6)alkoxy;
n is 0, 1, 2 or 3 and
m is 2 or 3.

12. The compound according to claim 1 represented by structural formula selected from:

or its pharmaceutically acceptable salt,
where R5denotes H or methyl;
R6denotes H, (C1-C7)alkyl, cyclohexylmethyl, galactically, gidroksilirovanii cyclohexylmethyl, (C1-C2)alkylcyclohexanes, (3-nidamental)methyl or (tetrahydropyranyl)methyl; and
R11denotes fluorine, chlorine, bromine, (C1-C6)alkyl, (C1-C6)-alkoxy;
n is 0, 1, 2 or 3 and
m is 2 or 3.

13. Connection § § 11 and 12, characterized in that R5denotes H or methyl;
R6 means (C1-C7)alkyl, cyclohexylmethyl, galactically, gidroksilirovanii cyclohexylmethyl, (C1-C2)alkylcyclohexanes, (3-nidamental)-methyl or (tetrahydropyranyl)methyl;
G denotes NH2or other7;
R7denotes methyl, or R5and R7together form a (CH2)3possibly substituted (C1-C4)alkyl or cyclohexyl.

14. The connection 13, represented by the following structural formula:

or its pharmaceutically acceptable salt.

15. The connection 13 represented by a structural formula selected from:

or its pharmaceutically acceptable salt.

16. Connection at one PP-10 and 13-15, wherein R9denotes methyl or ethyl and R11denotes chlorine, fluorine or methyl.

17. Connection P16 represented by the structural formula:

or its pharmaceutically acceptable salt.

18. Connection P16 represented by a structural formula selected from:





or its pharmaceutically acceptable salt.

19. A compound selected from the group, which include what it
methyl-(S)-4-(3-chlorophenyl)-4-((R)-1-((S)-1-cyclohexyl-3-(methylamino)-propane-2-ylcarbonyl)piperidine-3-yl)-4-hydroxybutylidene;
methyl-(S)-4-(3-chloro-5-forfinal)-4-((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)-4-hydroxybutylidene;
methyl-(S)-4-(3-chloro-5-forfinal)-4-((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)-4-hydroxybutylidene;
methyl-(S)-4-(3-chloro-2-forfinal)-4-((R)-1-((S)-1-(TRANS-4-forcelogix)-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)-4-hydroxybutylidene;
methyl-(S)-4-acetamido-4-(3-chlorophenyl)-4-((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)-4-BUTYLCARBAMATE;
methyl-(S)-4-(3-chlorophenyl)-4-((R)-1-((S)-1-cyclohexyl-3-(methylamino)-propane-2-ylcarbonyl)piperidine-3-yl)-4-Propionibacterium;
methyl-2-((R)-((R)-1-((S)-1-cyclohexyl-3-(methylamino)propan-2-yl-carbarnoyl)piperidine-3-yl)(3-forfinal)methoxy)ethylcarbamate;
methyl-2-((R)-((R)-1-((S)-1-amino-3-cyclohexylprop-2-ylcarbonyl)-piperidine-3-yl)(3-chlorophenyl)methoxy)ethylcarbamate;
methyl-2-((R)-(3-chlorophenyl)((R)-1-((S)-1-cyclohexyl-3-(methylamino)-propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate;
methyl-2-((R)-((R)-1-((2S,3R)-3-amino-1-cyclohexylmethyl-2-yl-carbarnoyl)piperidine-3-yl)(3-chlorophenyl)methoxy)ethylcarbamate;
methyl-2-((R)-((3R)-1-((2S)-1-cyclohexyl-3-(methylamino)propan-2-yl-carbarnoyl)piperidine-3-yl)(2,3-differenl)methoxyethylamine;
methyl-2-((R)-1-(3-chlorophenyl)-1-((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)ethoxy)ethylcarbamate;
methyl-2-((R)-(3-chloro-2-forfinal)((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate;
methyl-2-((R)-(3-chloro-2-forfinal)((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate;
methyl-2-((R)-(3-chloro-5-forfinal)((R)-1-((S)-1-cyclohexyl-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate;
methyl-2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(TRANS-4-forcelogix)-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate;
methyl-2-((R)-(3-chloro-2-forfinal)((R)-1-((S)-1-(TRANS-4-forcelogix)-3-(methylamino)propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate; and methyl-2-((R)-(3-chlorophenyl)((R)-1-((S)-1-(3-lordamantr)-3-(methylamino)-propane-2-ylcarbonyl)piperidine-3-yl)methoxy)ethylcarbamate or
pharmaceutically acceptable salt of any of the above compounds.

20. Pharmaceutical composition having activity against renin, including pharmaceutically acceptable carrier or diluent and a compound according to any one of claims 1 to 19 or its pharmaceutically acceptable salt.

21. How antagonization one or more aspartate proteases for a subject, in need thereof, comprising administration to the subject an effective amount of the program according to any one of claims 1 to 19 or its pharmaceutically acceptable salt.

22. The method according to item 21, wherein the aspartate protease is a renin.

23. The method of treatment mediated aspartate protease disorder of a subject, comprising introducing to a subject an effective amount of a compound according to any one of claims 1 to 19 or its pharmaceutically acceptable salt.

24. The method according to item 23, wherein the breach is hypertension, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, myocardial infarction after cardiomyopathy, nephropathy, a disorder of vessels, neuropathy, coronary artery disease, hypertension after surgery, restenosis after angioplastic, elevated intraocular pressure, glaucoma, abnormal growth of blood vessels, hyperaldosteronism, anxiety or cognitive disorder.

25. The compound represented by structural formula

or its pharmaceutically acceptable salt.

26. Pharmaceutical composition having activity against renin containing a pharmaceutically acceptable carrier or diluent and a compound represented by structural formula

or its pharmaceutically acceptable salt.

27. The method of treatment mediated aspartate protease disorder of a subject,comprising introducing to a subject an effective amount of the compounds represented by the structural formula

or its pharmaceutically acceptable salt.

28. The method according to item 27, wherein the breach is hypertension, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, myocardial infarction after cardiomyopathy, nephropathy, a disorder of vessels, neuropathy, coronary artery disease, hypertension after surgery, restenosis after angioplasty, elevated intraocular pressure, glaucoma, abnormal growth of blood vessels, hyperaldosteronism, anxiety or cognitive disorder.

29. The compound represented by structural formula

or its pharmaceutically acceptable salt.

30. Pharmaceutical composition having activity against renin containing a pharmaceutically acceptable carrier or diluent and a compound represented by structural formula

or its pharmaceutically acceptable salt.

31. The method of treatment mediated aspartate protease disorder of a subject, comprising introducing to a subject an effective amount of the compound represented by structural formula

or its pharmaceutically acceptable with the I.

32. The method according to p, characterized in that the breach is hypertension, congestive heart failure, cardiac hypertrophy, cardiac fibrosis, myocardial infarction after cardiomyopathy, nephropathy, a disorder of vessels, neuropathy, coronary artery disease, hypertension after surgery, restenosis after angioplasty, elevated intraocular pressure, glaucoma, abnormal growth of blood vessels, hyperaldosteronism, anxiety or cognitive disorder.

33. The connection represented by the structural formula:

or its pharmaceutically acceptable salt,
where Z denotes-O - or-CH2-;
X1denotes a covalent bond or-O-;
Y1denotes a covalent bond or C1-C10alkylene, provided that Y1is a covalent bond only when X1denotes a covalent bond;
E represents hydrogen, tert-butoxycarbonyl or benzyloxycarbonyl;
R2refers to-NHC(O)OR9where R9denotes a linear or branched C1-C5alkyl or linear or branched (C1-C5-alkoxyalkyl;
R3denotes H, C1-C5alkyl, -NHC(O)R10or is HE, where R10represents C1-C3alkyl, with the moustache is ovii, that when R3means is HE, then X1is Oh, and R2-Y1-X1is not-OC(O)(NH2), -OC(O)(other9), -NHC(O)OR9or-NHC(O)H;
n is 0, 1, 2 or 3;
R11denotes fluorine, chlorine, bromine, (C1-C6)alkyl, (C1-C6)-alkoxy.

34. Connection p represented by the structural formula:

or its pharmaceutically acceptable salt.

35. Connection p represented by the structural formula:

or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof, where Q is CH or N; R2 is C1-C4 alkyl or C3-C4-cycloalkyl; Y is R5-O; where R5 is propynyl; X is selected from a group consisting of aryl, heteroaryl, C1-C5-alkyloxy, heterocycloalkyl, arylamino, heteroarylamino, heteroaryl-C1-C4-alkylamino, aryloxy, aryl-C1-C2-alkyloxy or C3-C6-cycloalkyl-C1-C4-alkyloxy, each of which is optionally substituted with 1-3 times; the optional substitute(s) for X is(are) independently selected from a group comprising halogen, cyano, trifluoromethyl, nitro, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkyloxy-C1-C4-alkoxy, -SMe, SO2-C1-C2-alkyl, -NMe2, - C(O)O-C1-C5-alkyl, -SCF3, -SO2-NH2, -SO2-C2-alkyl-OH, -CONH2, -COMe, - CONH-C1-C4-alkyl, -CONMe2, -NHCOMe, -CH2COOEt, -OCH2COOEt, -CH2- cyclopropyl, and each R3 and R4 is H; where aryl denotes phenyl or naphthyl; heteroaryl denotes monocyclic or bicyclic hydrocarbon containing 5-10 ring atoms, one or more of which are heteroatoms selected from O, N or S; heterocyclyl denotes piperidinyl or benzodioxolyl; or a compound or pharmaceutically acceptable salt thereof, selected from a group comprising (4-dimethylaminophenyl)-[4-(4-cyclopropylphenyl)-6-propargyloxyquinazolin-2-yl]methanone, (3-sulphamoylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, [3-(2-hydroxyethanesulphonyl)phenyl]amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methylsulphanylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methanesulphonylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, and (5-ethanesulphonyl-2-hydroxyphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4- dihydroquinazoline -2-carboxylic acid. The invention also relates to a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel benzoquinazoline derivatives, which are useful in treating bone disorders, are obtained.

6 cl, 128 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-alkylamides of formula I

, where A is selected from such groups as -CH2-CH2-, -CH2-CH2-CH2- and -Y-CH2-CH2-, where Y is selected from O, S and NR11 and Y is bonded to a Het group; Het denotes a 5-member or 6-member monocyclic aromatic group which contains one or two identical or different heterocyclic ring elements selected from N, NR13 and S, and which can be substituted with one or more identical or different substitutes R5; X denotes a single bond; R1 and R2 together with a N-CO group which contains them, form a 4-10-member monocyclic or bicyclic saturated or unsaturated ring which, besides a nitrogen ring atom which is part of the N-CO group, can contain one or two additional heterocyclic ring elements selected from N, NR12, O and S, which can be identical or different, provided that two ring elements from O and S cannot be in neighbouring positions in the ring, where the ring, formed by R1 and R2 and the N-CO group containing them, can be substituted with one or more identical or different substitutes R8; R3 is selected from phenyl, naphthalinyl and heteroaryl, which all can be substituted with one or more identical or different substitutes selected from a halogen atom, (C1-C4)alkyl, (C1-C4)alkyloxy group, which can be substituted with one or more fluorine atoms, (C1-C4)alkylamino, di((C1-C4)alkyl)amino, ((C1-C4)alkyl)-CONH-, CONH2, CN, CF3, H2NSO2- and (C1-C4)alkyl-SO2-; R5 is selected from a halogen atom and (C1-C4)alkyl; R8 is selected from a halogen atom, (C1-C4)alkyl and an oxo-group; R11 denotes a hydrogen atom; R12 is selected from a hydrogen atom and (C1-C4)alkyl; R13 is selected from a hydrogen atom and (C1-C4)alkyl; heteraryl is a 5-member or 6-member monocyclic aromatic group which contains one, two or three identical or different heterocyclic ring elements selected from N, NR13, O and S; in any of its stereoisomeric forms or mixture of stereoisomeric forms in any ratio, or its physiologically acceptable salt; provided that the -N(R2)-CO-R1 group cannot be an unsubstituted 2-oxopyrrolidin-1-yl group or unsubstituted 2-oxoimidazolin-1-yl group if the -N(R2)-CO-R1 group simultaneously denotes a group of formula

,

in which the bond through which the group is bonded to group A, is denoted by a line starting from position 2 of the pyridine ring, and in which R90 is selected from imidazol-1-yl, isoxazol-5-yl, isothiazol-5-yl, 1,2,4-thiazol-1-yl, pyrazin-2-yl and pyrazol-3-yl, which can all be substituted with (C1-C4)alkyl and which can be substituted in the pyridine ring with at most four substitutes selected from (C1-C4)alkyl and a halogen atom; and provided that the -N(R2)-CO-R1 cannot be a 1,3-dioxoisoindol-2-yl group of formula

in which the bond through which the group is bonded to group A is denoted by a line beginning from the nitrogen atom. The invention also relates to a method of producing said compounds, a pharmaceutical composition for stimulating endothelia NO synthase, as well as to use thereof in preparing a medicinal agent.

EFFECT: novel compounds which can be used in conditions where high expression of the said enzyme, high content of NO or normalisation of low content of NO is desired are obtained and described.

18 cl, 87 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I and to its pharmaceutically acceptable salts. In formula I , R1 means hydrogen or ; is specified from phenyl, and a 5-member heteroaromatic ring containing 1 to 2 heteroatoms specified inhe group consisting of sulphur and nitrogen; X is specified from lower alkylene, cyclisated lower alkylene containing 3 to 6 carbon atoms, and hydroxy(lower alkylene); R5 and R6 are independently specified in the group including hydrogen, lower alkyl, halogen and lower alkoxygroup; R3 is specified from hydrogen and -NH-R7; R4 is specified from hydrogen and -O(CH2CH2O)y-R10; R7 means lower alkyl; R10 means lower alkyl; n means an integer within 0 to 1; and y is equal to 0; provided when n is equal to 0, and R1 means hydrogen, then R3/R4 both cannot mean hydrogen. The invention also concerns a pharmaceutical composition containing a therapeutically effective amount of the compound under the invention.

EFFECT: preparation of the new compounds which show CDK1 kinase inhibiting activity and can be effective in cancer treatment, particularly breast cancer, lung cancer, colon cancer and prostate cancer treatment.

45 cl, 21 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I and to its pharmaceutically acceptable salts. In formula I , Y means -S- or -NH-; R1 is specified from hydrogen, -C(O)O-[CH2CH2O]P-R4, -C(O)-R3 and R2-(X)n-; R3 is specified from lower alkyl, cycloalkyl containing 3 to 6 carbon atoms and ; R4 means lower alkyl; X is specified from lower alkylene and cyclisated lower alkylene; R2 means ; where is specified from phenyl, and a 5 or 6-merous heteroaromatic ring containing 1 to 2 heteroatoms specified in the group consisting of sulphur and nitrogen; R5 and R6 are independently specified in the group including hydrogen, lower alkyl, halogen, perfluor (lower alkyl) and lower alkoxygroup; n means an integer within 1 to 2; and r means 0. The invention also concerns a pharmaceutical composition containing a therapeutically effective amount of the compound under the invention.

EFFECT: preparation of the new compounds which show CDK1 kinase inhibiting activity and can be effective in cancer treatment, particularly breast cancer, lung cancer, colon cancer and prostate cancer treatment.

64 cl, 27 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel compounds which possess inhibiting properties with respect to PI3-kinase of general formula (1), where R1 is selected from group, including -NHRC, -NHC(O)Rc, -NHC(O)ORc, -NHC(O)NRcRc and -NHC(O)SRc, R2 stands for residue, optionally substituted with one or two substituents R4, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, 5-6-member heterocycloalkyl with one heteroatom, selected from nitrogen and sulphur, phenyl, benzyl and 5-6-member heteroaryl, including 1-2 nitrogen atoms, R3 stands for optionally substituted with one or several substituents Re and/or Rf residue, selected from group, including phenyl and 5-6-member heteroaryl with 1-3 heteroatoms, selected from nitrogen and oxygen, R4 represents residue, selected from group, including Ra, Rb, and substituted with one or several identical or different substituents Rc and/or Rb , Ra in each case is independently selected from group, including C1-C6alkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 9-member heteroaryl with one atom of nitrogen as heteroatom, Rb in each case is independently selected from group, including =O, -ORc, -NRCRC, halogen, -CF3, -CN, -S(O)Rc, -C(O)Rc, -C(O)ORc, -C(O)NRcRc, -C(O)N(Rg)NRcRc, -N(Rg)C(O)Rc, -N(Rg)S(O)2Rc, -N(Rg)S(O)2NRcRc, -N(Rg)C(O)ORc and -N(Rg)C(O)NRcRc, RC in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents R and/or Re residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, C6-C9aryl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 5-6-member heteroaryl with 1-2 heteroatoms, selected from nitrogen, oxygen and sulphur, Rd in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents Re and/or Rf residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen, and 5-10-member heteroaryl with one atom of nitrogen, Re in each case is independently selected from group, including =O, -ORf, -SRf, -NRfRf, -CN, -S(O)2Rf, -C(O)Rf, -C(O)ORf, -C(O)NRfRf and -OC(O)Rf, Rf in each case independently represents hydrogen or optionally substituted with one or two identical or different substituents Rg residue, selected from group, including C1-C6alkyl, C3-C8cycloalkyl, phenyl, 4-7-member heterocycloalkyl with 1-2 heteroatoms, selected from nitrogen and oxygen and 5-6-member heteroaryl with one heteroatom, selected from nitrogen and sulphur, Rg in each case independently represents hydrogen, C1-C6alkyl, C3-C8cycloalkyl and 4-7-member heterocycloalkyl with one nitrogen as heteroatom, as well as to their pharmaceutically harmless acid-additive salts. Invention also relates to compounds, used as intermediate products of synthesis of formula (I) compounds, pharmaceutical composition and application of compounds for preparation of medication, possessing properties of PI3-kinase inhibitor.

EFFECT: elaborated are novel compounds, which possess properties of PI3-kinase inhibitor.

11 cl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 2-[(1Z)-1-(3,5-diphenyl-1,3,4-thiadiazol-2(3H)-ylidene)methyl]-3,5-diphenyl-1,3,4-thiadiazol-3-ium chloride of formula I . The invention also relates to a method for synthesis of the said compound.

EFFECT: obtaining a novel chemical compound which can be used in synthesis of novel heterocyclic compounds and in medicine as a potential antibacterial agent.

2 cl, 1 dwg, 6 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.

EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.

11 cl, 30 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) , where Z means where R means hydrogen, C4-C6cycloalkyl group attached either through one of ring carbon atoms, or through a lower alkylene group attached to the ring, or a linearly chained or branched lower alkyl group or a lower hydroxyalkyl group, or a lower aminoalkyl group, or a phenyl(lower alkyl) group optionally substituted with 1-2 substitutes chosen from lower alkyl, lower alkoxy, halogen and hydroxy, or heteroaryl(lower alkyl)group where heteroaryl is chosen from the group consisting from thienyl, substituted with lower alkyl group, imidazolyl, and thiazolyl substituted with the lower alkyl group; n means 0 or 1; or Z means a group where R means the lower alkyl group; X1 means methylene or NH group; and X2 means methylene; or X1 means methylene and X2 means methylene or a bond; or X1 means methylene, and X2 means O, S or a bond; Y1 means methylene, and Y2 means methylene, vinylene, ethylene, or a bond; Ar1 means unsubstituted or substituted phenyl; Ar2 means unsubstituted or substituted phenyl, unsubstituted or substituted thienyl, unsubstituted or substituted furyl, unsubstituted or substituted pyridyl; and when Ar1 and Ar2 are substituted, each Ar1 and Ar2 are independently substituted with one or more substituted chosen from lower alkyl, lower alkoxy, hydroxy, lower hydroxyalkyl, halogen, di- and trihaloalkyl, di- and trihaloalkoxy, mono- and dialkylamino, alkilthio, alkyl ester and nitro; provided that Ar1 and Ar2 do not simultaneously mean unsubstituted phenyl; W means oxygen or sulphur; or to their pharmaceutically acceptable salts; provided those specified in cl. 1 of the patent claim. Besides the invention concerns the compounds chosen from the group, to compounds of formula (I), to pharmaceutical compositions, to a method of inhibition of monoamine receptor activity, to a method of inhibition of monoamine receptor activation, to a method of treating a diseased state associated with serotonin receptor, to a method of treating schizophrenia, to a method of treating migraine, and also to a method of treating psychosis.

EFFECT: preparation of the new biologically active compounds capable to inhibit monoamine receptor activity.

65 cl, 140 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula I and their pharmaceutically acceptable salts. Disclosed compounds have inhibitory effect on CDK1 kinase and can be used to prepare medicinal agents for treating diseases associated with abnormal cell cycle development. In formula I , R1 is hydrogen, -C(O)OR9 or R2-(X)n-; X is (lower)alkylene, hydroxy(lower)alkylene, cyclised(lower)alkylne or mono- or dihalogen(lower)alkylene; R2 is a group, where denotes a phenyl or a 5-6-member heteroaromatic ring containing 1-2 heteroatoms selected from a group comprising oxygen, sulphur and nitrogen atoms; R5, R6 and R7 are independently selected from a group comprising hydroxy, hydrogen, (lower)alkyl, halogen and (lower)alkoxy; R4 is a halogen, , (O)k(CH2CH2O)y-R10, , -S-R12 or -O-(CH2)tR14, where denotes a phenyl, a cycloalkyl ring containing 3-6 carbon atoms, a 4-6-member heterocycloalkyl containing 3-5 carbon atoms and 1-2 heteroatoms selected from a group comprising oxygen, nitrogen and sulphur atoms; R9, R11, R15 and R16 independently denote (lower)alkyl; R10 and R12 denote (lower)alkyl; R14 denotes perfluoro(lower)alkyl or -NR15R16; R17 and R18 independently denote hydrogen, , F, OCH3 and -C(=O)CH3; n and k are equal to 0 or 1; m, w, y and z are equal an integer from 0 to 3; and t equals an integer from 0 to 6.

EFFECT: invention also relates to a pharmaceutical composition having antiproliferative activity, containing one or more of the disclosed compounds.

65 cl, 1 tbl, 49 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described compounds of 3-cyanonaphthalene-1-carboxylic acid and perhydroxyalkylmethylpiperazine of formula

, where R1 means C1-C4alkyl, R2 and R3 mean halogen, R4 is selected from the group consisting of 2-furanyl, 3-furanyl, 2-thiophen, 3-thiophen, phenyl, benzyl, 2-benzofuranyl, etc., R5 is selected from the group consisting of hydrogen and R6, R6 means a subgroup of general formula

which are antagonists of tachykinin receptors. Also, there are described pharmaceutical compositions containing such compounds, and methods for making such compounds and intermediate products for making the compounds according to said methods.

EFFECT: preparation of new compounds.

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula (I) or pharmaceutically acceptable salts thereof, where Q is CH or N; R2 is C1-C4 alkyl or C3-C4-cycloalkyl; Y is R5-O; where R5 is propynyl; X is selected from a group consisting of aryl, heteroaryl, C1-C5-alkyloxy, heterocycloalkyl, arylamino, heteroarylamino, heteroaryl-C1-C4-alkylamino, aryloxy, aryl-C1-C2-alkyloxy or C3-C6-cycloalkyl-C1-C4-alkyloxy, each of which is optionally substituted with 1-3 times; the optional substitute(s) for X is(are) independently selected from a group comprising halogen, cyano, trifluoromethyl, nitro, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkyloxy-C1-C4-alkoxy, -SMe, SO2-C1-C2-alkyl, -NMe2, - C(O)O-C1-C5-alkyl, -SCF3, -SO2-NH2, -SO2-C2-alkyl-OH, -CONH2, -COMe, - CONH-C1-C4-alkyl, -CONMe2, -NHCOMe, -CH2COOEt, -OCH2COOEt, -CH2- cyclopropyl, and each R3 and R4 is H; where aryl denotes phenyl or naphthyl; heteroaryl denotes monocyclic or bicyclic hydrocarbon containing 5-10 ring atoms, one or more of which are heteroatoms selected from O, N or S; heterocyclyl denotes piperidinyl or benzodioxolyl; or a compound or pharmaceutically acceptable salt thereof, selected from a group comprising (4-dimethylaminophenyl)-[4-(4-cyclopropylphenyl)-6-propargyloxyquinazolin-2-yl]methanone, (3-sulphamoylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, [3-(2-hydroxyethanesulphonyl)phenyl]amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methylsulphanylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methanesulphonylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, and (5-ethanesulphonyl-2-hydroxyphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4- dihydroquinazoline -2-carboxylic acid. The invention also relates to a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel benzoquinazoline derivatives, which are useful in treating bone disorders, are obtained.

6 cl, 128 ex

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: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of formula I: where: R1 represents R6C(O)-, R6SO2-, (R6)2NC(O)-; R2 represents hydrogen, -CF3 or R8; R3 represents -T-R9; R4 represents -COOH or -COOR8; R5 represents -CH2F or -CH2O-2, 3, 5, 6 - tetrafluorophenyl; R6 represents R6a or R6b; two R6 groups, together with the atom to which they are bound optionally form 3-10-member aromatic or non-aromatic ring; and where each R6 is independently substituted with 6 substituents, independently selected from R; R6a and R6b each independently represents (C1-C3)-aliphatic group, (C6-C10)-aryl-, (C6-C10)-aryl-(C1-C12) aliphatic group; R represents halogen, -OR7, -R7; each R7 is independently selected from: hydrogen, (C1-C12)-aliphatic group, (C6-C10)-aryl; R8 represents (C1-C12)-aliphatic group; T represents direct bond or (C1-C6)-aliphatic group, where to 2 aliphatic carbon atoms in T can be optionally substituted with O; R9 is optionally substituted (C6-C10)-aryl or (C5-C10) - heteroaryl, invention also relates to pharmaceutical composition, to methods of treatment, inhibition of caspase-mediated processes, to method of cell preservation with application of formula I compounds application of such compositions for treatment of caspase-mediated diseases and to methods of obtaining formula I compounds.

EFFECT: obtained and described are novel compounds, which can be useful in treatment of caspase-mediated diseases.

38 cl, 22 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) , where Z means where R means hydrogen, C4-C6cycloalkyl group attached either through one of ring carbon atoms, or through a lower alkylene group attached to the ring, or a linearly chained or branched lower alkyl group or a lower hydroxyalkyl group, or a lower aminoalkyl group, or a phenyl(lower alkyl) group optionally substituted with 1-2 substitutes chosen from lower alkyl, lower alkoxy, halogen and hydroxy, or heteroaryl(lower alkyl)group where heteroaryl is chosen from the group consisting from thienyl, substituted with lower alkyl group, imidazolyl, and thiazolyl substituted with the lower alkyl group; n means 0 or 1; or Z means a group where R means the lower alkyl group; X1 means methylene or NH group; and X2 means methylene; or X1 means methylene and X2 means methylene or a bond; or X1 means methylene, and X2 means O, S or a bond; Y1 means methylene, and Y2 means methylene, vinylene, ethylene, or a bond; Ar1 means unsubstituted or substituted phenyl; Ar2 means unsubstituted or substituted phenyl, unsubstituted or substituted thienyl, unsubstituted or substituted furyl, unsubstituted or substituted pyridyl; and when Ar1 and Ar2 are substituted, each Ar1 and Ar2 are independently substituted with one or more substituted chosen from lower alkyl, lower alkoxy, hydroxy, lower hydroxyalkyl, halogen, di- and trihaloalkyl, di- and trihaloalkoxy, mono- and dialkylamino, alkilthio, alkyl ester and nitro; provided that Ar1 and Ar2 do not simultaneously mean unsubstituted phenyl; W means oxygen or sulphur; or to their pharmaceutically acceptable salts; provided those specified in cl. 1 of the patent claim. Besides the invention concerns the compounds chosen from the group, to compounds of formula (I), to pharmaceutical compositions, to a method of inhibition of monoamine receptor activity, to a method of inhibition of monoamine receptor activation, to a method of treating a diseased state associated with serotonin receptor, to a method of treating schizophrenia, to a method of treating migraine, and also to a method of treating psychosis.

EFFECT: preparation of the new biologically active compounds capable to inhibit monoamine receptor activity.

65 cl, 140 ex, 5 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a novel compound N-(1-{(3R)-3-(3,5-difluorophenyl)-3-[1-(methylsulfonyl) piperidin-4-yl]propyl}piperidin-4-yl)-N-ethyl-2-[4- (methylsufonyl)phenyl]acetamide or its pharmaceutically acceptable salts. The invention also relates to a method for synthesis of the compound in paragraph 1, as well as to a pharmaceutical composition.

EFFECT: obtaining a novel biologically active compound with activity towards CCR5 (chemokine receptor 5).

6 cl, 6 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: new method is described for producing new derivatives in the series 5-amino-2,4-dihydro-3N-1,2,4-triazole-3-thiones, and specifically to a method of producing 4,5-disubstituted 2,4-dihydro-3N-1,2,4-triazole-3-thiones with general formula I: , where R1=C1-C6 alkylphenyl, haloid phenyl, thienyl, furanyl or pyrrolyl; R2= phenyl C1-C6 alkyl, naphthyl C1-C6 alkyl, anthryl C1-C6 alkyl, C1-C6 alkoxyphenyl, which involves reaction of corresponding acylisothiocyanates, obtained from acylchlorides R1-C(O)Cl and ammonium rhodanide, with 4-R2- thiosemicarbazides R2-NH-C(S)-NH-NH2 and subsequent cyclisation of N-[2-(R2- carbamothioyl) hydrazinocarbonothioyl]acylamides in a medium of high-boiling aliphatic alcohols.

EFFECT: desired product, which is obtained with high output and purity, can be used in medicine.

1 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new benzimidazole derivatives with general formula (I), where A represents -CH2-, -C(O), -C(O)-C(Ra)(Rb)-, X represents a -CH- radical; Ra and Rb independently represent a hydrogen atom or (C1-C6)alkyl radical; R1 represents a hydrogen atom or (C1-C8)alkyl radical; R2 represents a (C1-C8)alkyl radical; R3 represents -(CH2)P-Z3, -C(O)-Z'3 or -C(O)-NH-Z"3; Z3 represents (C1-C6)alkyl, (C2-C6)alkenyl, (C1-C6)alkoxy, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C1-C6)alkyl-N(RN)carbonyl, (C3-C7)cycloalkyl, aryl, arylthio or heteroaryl radical, Z3 is bonded to the -(CH2)P- through a carbon atom, heteroaryl radical, which is a 5-10- member heteroaryl, which contains 1-2 identical or different heteroatoms, chosen from sulphur, nitrogen or oxygen, and optionally substituted with one or more identical or different substitutes, chosen from halogen, nitro group or -(CH2)P'-V30-Y3; aryl radical, chosen from phenyl or naphthyl, optionally substituted with one or more identical or different substitutes, chosen from halogen, nitro group, cyano group, (C2-C6)alkenyl, pyrrolidinyl, phenyl, phenyloxy, phenylalkyloxy, 5-7- member heteroaryl, containing 1-3 nitrogen atoms and -(CH2)p'-V31-Y3; V30 represents -O-, -C(O)-, -C(O)-O- or a covalent bond; V31 represents -O-, -S-, -SO2-, -C(O)-, -C(O)-O-, -N(RN)-, -NH-C(O)- or a covalent bond; Y3 represents a hydrogen atom or (C1-C6)alkyl radical, optionally substituted with one or more identical or different halogen radicals; RN represents a hydrogen atom or (C1-C6)alkyl radical; Z3 represents a radical with a given formula (see below); Z'3 represents a phenyl radical, optionally substituted with one ore more identical or different substitutes, chosen from -(CH2)P"-V'3-Y'3; V'3 represents -O-; Y'3 represents a hydrogen atom or (C1-C6)alkyl radical; Z"3 represents a hydrogen atom or -(CH2)q-A"3 radical; A"3 represents (C1-C6)alkyl, phenyl or thienyl radical; alkyl or phenyl radical can be optionally substituted with one or more identical or different substitutes, chosen from halogen and -V"3-Y"3; V"3 represents -O-, -C(O)-, -C(O)-O- or a covalent bond; Y"3 represents a hydrogen atom or (C1-C6)alkyl radical; p is an integer from 0 to 6; p' and p" independently represent an integer from 0 to 1; q is an integer from 0 to 2; R4 represents a radical with formula -(CH2)S-R'4; R'4 represents a 5-7- member heterocycloalkyl, containing at least one nitrogen atom and optionally substituted with (C1-C6)alkyl; or a radical with formula -NW4W'4; W4 represents a hydrogen atom; W'4 represents a hydrogen atom; s is an integer from 0 to 6; in racemic or enantiomeric form or any combination of the said forms, or its pharmaceutically acceptable salt. The invention also relates to a method of obtaining a compound in paragraph 1, a pharmaceutical composition based on the said compound and its use in making a medicinal agent.

EFFECT: new benzimidazole derivatives have good affinity to certain subtypes of melanocortin receptors.

26 cl, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to formula (I) compounds and to their use in treating diseases related to lipid storage disorders, such as atherosclerosis and diabetes. In R1 represents hydrogen, alkyl, halogen, formyl, hydroxyalkyl or trifluoromethyl, R2 represents hydrogen, alkyl or halogen, R3 represents hydrogen or alkyl, R4 represents hydrogen, alkyl, hydroxy or alkoxy, R5 and R6 are chosen from hydrogen, alkyl, phenylalkyl, hydroxyalkyl, alkoxycarbonyl and phenyl, A represents aryl or heterocyclyl, m equals 0-3, n equals 0-1, p equals 0-3, sum of m, n and p equals 1-4, the bond between carbon atoms Ca and Cb is a single or double carbon-carbon bond.

EFFECT: obtaining new biologically active compounds.

27 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: described is compound representing 2,5-disubstituted 3-mercaptopentanic acid of formula (I) or its pharmaceutically acceptable salt, where R' represents phenyl, possibly substituted, naphtyl, pyridinyl, 1,2,3,4-tetrahydropyrimidine-2,4-dion-yl, substituted with C1-4alkyl, or tetrahydrothienyl; R2 represents aminopyridinyl, aminothiazolyl or 3-azabicyclo[3.2.1]octyl; R3 represents C1-4alkoxy, possibly substituted with phenyl (substituted with halogen) or pyridinyl; NR5R6 or N-bonded 5- or 6-member heterocyclic ring representing pyrrolidinyl, piperidinyl or piperazinyl ring, non-substituted or monosubstituted, or condensed with benzene ring, which is possibly substituted with C1-4alkoxy; R4 represents N-bonded pyrrolidinyl ring, monosubstituted with C1-4alkyl, which is substituted with NHphenyl; R5 and R6 independently represent hydrogen, C1-4alkyl, possibly substituted, or C2-4alkenyl; and method of obtaining it.

EFFECT: obtaining compounds inhibiting carboxypeptidase and which can be used in prevention and treatment of diseases in which inhibiting carboxypeptidase is useful.

7 cl, 1 tbl, 53 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

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