Benzamide derivatives as oxytocin agonists and vasopressin antagonists

FIELD: chemistry.

SUBSTANCE: novel compounds are selected from group, consisting of: 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl- 4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihudro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluorine-4-(3-methyl-4,10-dihydro-3H-2,3,4;9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide; 4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chlorine-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamide and 4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraazabenzo[f]azulene-9-carbonyl)-benzylamide. Invention also relates to pharmaceutical composition and to application of compounds of general formula 1.

EFFECT: obtaining novel biologically active compounds and based on them pharmaceutical composition, possessing antagonistic activity with respect to vasopressin receptors.

60 cl, 153 ex

 

The text descriptions are given in facsimile form.

1. A compound selected from the group consisting of

4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine--carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f|azulene-9-carbonyl)-benzylamine;

4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine; and

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine.

2. Pharmaceutical composition having antagonistic activity against vasopressinergic receptors containing the compound according to claim 1 as an active agent.

3. The pharmaceutical composition according to claim 2, prepared in the form of tablets or capsules for oral administration.

4. The pharmaceutical composition according to claim 2 or 3 for the treatment of primary dysmenorrhea.

5. The pharmaceutical composition according to claim 2 or 3 for the treatment of preterm labor, hypertension, diseases of Reinol is a, brain oedema, motion sickness, small-cell lung cancer, depression, anxiety, hyponatremia, liver cirrhosis or congestive heart failure.

6. The use of compounds of General formula 1 or its pharmaceutically acceptable salt

where - G1selected from the group of the General formula 2, a group of General formula 3, a group of General formula 4, a group of General formula 5, a group of General formula 6 and the group of General formula 7

And1selected from CH2CH(OH), NH, N-alkyl, O and S;

And2selected from CH2CH(OH), C(=O) and NH;

And3selected from S, NH, N-alkyl, -CH=CH - or CH=N-;

each And4and5selected from CH or N;

And6selected from CH2, NH, N-alkyl or O;

And7and11selected from C or N;

And8and9selected from CH, N, NH, N(CH2)dR7or S;

And10selected from-CH=CH-, CH, N, NH, N-(CH2)d-R7or S;

And12and13selected from N and C;

And14And15and16selected from NH, N-CH3, S, N and CH;

X1selected from O and NH;

each R1, Rsup> 2and R3selected from H, alkyl, O-alkyl, F, Cl and Br;

R4selected from H, alkyl, alkenyl, quinil, possibly substituted phenyl, possibly substituted tanila, possibly substituted Furie, possibly substituted pyridyl, possibly substituted pyrrolyl, possibly substituted pyrazolyl, possibly substituted imidazolyl, possibly substituted oxazolyl, possibly substituted isoxazolyl, possibly substituted thiazolyl, possibly substituted isothiazole, -(CHz)eR8, -CH2-CH=CH-CH2-R8, -CH2-C≡C-CH2-R8, -(CH2)g-CH(OH)-(CH2)h-R8, -(CH2)i-O-(CH2)j-R8and;

R5and R6independently from each other selected from alkyl, Ar, and -(CH2)fAr;

R7selected from H, alkyl, possibly substituted phenyl, F, HE, O-alkyl, O-acyl, S-alkyl, NH2, NH-alkyl, N(alkyl)2, NH-acyl, N(alkyl)-acyl, CO2N, CO2-alkyl, CONH2, CONH-alkyl, CON(alkyl)2CN and CF3;

R8selected from H, alkyl, alkenyl, quinil, acyl, possibly substituted phenyl, possibly substituted pyridyl, possibly substituted tanila, possibly substituted Furie, possibly substituted pyrrolyl, possibly substituted pyrazolyl, possibly substituted imidazolyl, perhaps C is displaced oxazolyl, possibly substituted isoxazolyl, possibly substituted thiazolyl, possibly substituted isothiazole, F, HE, hydroxyalkyl, O-alkyl, O-acyl, S-alkyl, NH2, NH-alkyl, N(alkyl)2, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, NH-acyl, N(alkyl)-acyl, N3, CO2H, CO2-alkyl, CONH2, CONH-alkyl, CON(alkyl)2CN and CF3;

Ar is selected from a possibly substituted tanila and possibly substituted phenyl;

and is 1 or 2, b is 1, 2 or 3; C is 1 or 2, d is 1, 2 or 3; e is 1, 2, 3 or 4; f is 1, 2 or 3, and g, h, i and j are independently from each other equal to 1 or 2;

provided that

not more than one And8And9and10represents NH, N(CH2)dR7or S;

And7and11both are not simultaneously N;

no And7nor And11are not N, if one of the A8And9and10represents NH, N(CH2)dR7or S;

if a10is not-CH=CH-, then one of the A8And9and10represents NH, N(CH2)dR7or S, or one of the A7and11represents N;

not more than one And14And15and16represents NH, N-CH3or S;

And12and13both are not simultaneously N;

if one of the A14And15and6 represents NH, N-CH3or S, And12and13both are C; and

one of the A14And15and16represents NH, N-CH3or S, or one of the A12and13represents N,

for the manufacture of pharmaceutical compositions for the treatment of primary dysmenorrhea.

7. The use of compounds of General formula 1 or its pharmaceutically acceptable salt,

where G1selected from the group of the General formula 2, a group of General formula 3, a group of General formula 4, a group of General formula 5, a group of General formula 6 and the group of General formula 7

And1selected from CH2CH(OH), NH, N-alkyl, O and S;

And2selected from CH2CH(OH), C(=O) and NH;

And3selected from S, NH, N-alkyl, -CH=CH - or CH=N-;

each And4and5selected from CH or N;

And6selected from CH2, NH, N-alkyl or O;

And7and11selected from C or N;

And8and9selected from CH, N, NH, N(CH2)dR7or S;

And10selected from-CH=CH-, CH, N, NH, N-(CH2)d-R7or S;

sup> 12and13selected from N and C;

And14And15and16selected from NH, N-CH3, S, N and CH;

X1selected from O and NH;

each R1, R2and R3selected from H, alkyl, O-alkyl, F, Cl and Br;

R4selected from H, alkyl, alkenyl, quinil, possibly substituted phenyl, possibly substituted tanila, possibly substituted Furie, possibly substituted pyridyl, possibly substituted pyrrolyl, possibly substituted pyrazolyl, possibly substituted imidazolyl, possibly substituted oxazolyl, possibly substituted isoxazolyl, possibly substituted thiazolyl, possibly substituted isothiazole, -(CH2)eR8, -CH2-CH=CH-CH2-R8, -CH2With≡-CH2-R8, -(CH2)g-CH(OH)-(CH2)h-R8, -(CH2)i-O-(CH2)j-R8and;

R5and R6independently selected from alkyl, Ar, and -(CH2)f-Ar;

R7selected from H, alkyl, possibly substituted phenyl, F, HE, O-alkyl, O-acyl, S-alkyl, NH2, NH-alkyl, N(alkyl)2, NH-acyl, N(alkyl)-acyl, CO2N, CO2-alkyl, CONH2, CONH-alkyl, CON(alkyl)2CN and CF3;

R8selected from H, alkyl, alkenyl, quinil, acyl, possibly substituted phenyl, possibly substituted pyridyl may replace the military tanila, probably replaced Furie, possibly substituted pyrrolyl, possibly substituted pyrazolyl, possibly substituted imidazolyl, possibly substituted oxazolyl, possibly substituted isoxazolyl, possibly substituted thiazolyl, possibly substituted isothiazole, F, HE, hydroxyalkyl, O-alkyl, O-acyl, S-alkyl, NH2, NH-alkyl, N(alkyl)2, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, NH-acyl, N(alkyl)-acyl, N3, CO2H, CO2-alkyl, CONH2, CONH-alkyl, CON(alkyl)2CN and CF3;

Ar is selected from a possibly substituted tanila and possibly substituted phenyl;

and is 1 or 2, b is 1, 2 or 3; C is 1 or 2, d is 1, 2 or 3; e is 1, 2, 3 or 4; f is 1, 2 or 3, and g, h, i and j are independently from each other equal to 1 or 2;

provided that

not more than one And8And9and10represents NH, N(CH2)dR7or S;

And7and11both are not simultaneously N;

no And7nor And11are not N, if one of the A8And9and10represents NH, N(CH2)dR7or S;

if a10is not-CH=CH-, then one of the A8And9and10represents NH, N(CH2)dR7or S, or one of the A7and11represents N;

not more than one And14And1 and16represents NH, N-CHCor S;

And12and13both are not simultaneously N;

if one of the A14And15and16represents NH, N-CH3or S, And both12and13represents S; and

one of the A14And15and16represents NH, N-CH3or S, or one of the A12and13represents N,

for the manufacture of pharmaceutical compositions for the treatment of preterm labor, hypertension, disease Reinhold, brain oedema, motion sickness, small-cell lung cancer, depression, anxiety, hyponatremia, liver cirrhosis or congestive heart failure.

8. The use according to claim 6 or 7, where at least one of R1, R2and R3represents N and at least one is N.

9. The use according to claim 6 or 7, where one of R1, R2and R3selected from the group alkyl, O-alkyl, F, Cl and Br, while others are N.

10. The use according to claim 6 or 7, where X1represents NH.

11. The use according to claim 6 or 7, where a is 1 and b is 2.

12. The use according to claim 6 or 7, where G1is a group of the General formula 3.

13. The application indicated in paragraph 12, where C is 2.

14. The application of section 12, where a1represents CH2and2represents NH.

15. Use para.12, gdea 1represents NH or N-alkyl, and2represents C(=O).

16. The application of section 12, where a3represents S, and4and5both represent CH.

17. The application of section 12, where a3represents-CH=CH-, and4and5both represent CH.

18. The application of section 12, where a3represents-CH=N-, and4and5both represent CH.

19. The application of section 12, where a3represents-CH=CH-, And4represents CH, and5represents N.

20. The use according to claim 6 or 7, where G1is a group of General formula 6 or 7.

21. The application of claim 20, where a3represents S, and both And4and5represent CH.

22. The application of claim 20, where a3represents-CH=CH-, and both And4and5represent CH.

23. The application of claim 20, where a3represents-CH=N-, and both And4and5represent CH.

24. The application of claim 20, where a3represents-CH=CH-, And4represents CH, and5represents N.

25. The use according to claim 6 or 7, where G1is a group of General formula 4 or 6.

26. Use A.25, where a6represents NH.

27. Application on p. 25 or 26, where a8represents NH or N-(CH2)d-R7

28. the label on item 27, where a9represents N and10represents CH.

29. The use according to claim 6 or 7, where one of R1, R2and R3selected from the group alkyl, O-alkyl, F, Cl and Br, and the other represents H, and X1represents NH.

30. The use according to any one of p or 7, where one of R1, R2and R3selected from the group alkyl, O-alkyl, F, Cl and Br, and the other represents H, and X1represents NH, and a is 1 and b is 2.

31. The use according to claim 6 or 7, where G1is a group of General formula 6, And4And5and10represent CH, And6represents NH, And7and11both represent C And8represents N-(CH2)d-R7and9represents N.

32. The use according to claim 6 or 7, where R1represents a group of alkyl, O-alkyl, F, Cl or Br, R2and R3both represent H, X1represents NH, and a is 1, b is 2, G1represents a group of General formula 6, And4And5and10all are CH, And6represents NH, And7and11both represent C And8represents N-(CH2)d-R7and9represents N.

33. The use according to claim 6 or 7, where the specified connection selected from the group consisting of:

4-cyclopropa the methyl-piperazine-1-carboxylic acid 2-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-(3,3-dimethyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-(3-methylsulfanyl-propyl)-piperazine-1-carboxylic acid 2-methyl-

4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid

2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(3-methyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

4-cyclohexylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-Methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-pentyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-hexyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

(R)-4-(2-methyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-(2-ethyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-methyl-but-2-enyl)-piperaz the n-1-carboxylic acid 2-methyl-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-

benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chloro-4-(3-methyl-

4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine; and

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-

methyl-4,10-dihydro-3H-2,3,4,9-t is triaza-benzo[f]azulene-9-carbonyl)-

benzylamine.

34. The use of compounds of General formula 1 or its pharmaceutically acceptable salt

where G1selected from the group of the General formula 2, a group of General formula 3, a group of General formula 4, a group of General formula 5, a group of General formula 6 and the group of General formula 7

And1selected from CH2CH(OH), NH, N-alkyl, O and S;

And2selected from CH2CH(OH), C(=O) and NH;

And3selected from S, NH, N-alkyl, -CH=CH - or CH=N-;

each And4and5selected from CH or N;

And6selected from CH2, NH, N-alkyl or O;

And7and11selected from C or N;

And8and9selected from CH, N, NH, N(CH2)dR7or S;

And10selected from-CH=CH-, CH, N, NH, N-(CH2)d-R7or S;

And12and13selected from N and C;

And14And15and16selected from NH, N-CH3, S, N and CH;

X1selected from O and NH;

each R1, R2and R3selected from H, alkyl, O-alkyl, F, Cl and Br;

R4selected from H, alkyl, alkenyl, quinil possibly samewe the aqueous phenyl, possibly substituted tanila, possibly substituted Furie, possibly substituted pyridyl, possibly substituted pyrrolyl, possibly substituted pyrazolyl, possibly substituted imidazolyl, possibly substituted oxazolyl, possibly substituted isoxazolyl, possibly substituted thiazolyl, possibly substituted isothiazole, -(CH2)eR8, -CH2-CH=CH-CH2-R8, -CH2With≡C-CH2-R8, -(CH2)g-CH(OH)-(CH2)h-R8, -(CH2)i-O-(CH2)j-R8and;

R5and R6independently selected from alkyl, Ar, and -(CH2)f-Ar;

R7selected from H, alkyl, possibly substituted phenyl, F, HE, O-alkyl, O-acyl, S-alkyl, NH2, NH-alkyl, N(alkyl)2, NH-acyl, N(alkyl)-acyl, CO2N, CO2-alkyl, CONH2, CONH-alkyl, CON(alkyl)2CN and CF3;

R8selected from H, alkyl, alkenyl, quinil, acyl, possibly substituted phenyl, possibly substituted pyridyl, possibly substituted tanila, possibly substituted Furie, possibly substituted pyrrolyl, possibly substituted pyrazolyl, possibly substituted imidazolyl, possibly substituted oxazolyl, possibly substituted isoxazolyl, possibly substituted thiazolyl, possibly substituted isothiazole, F, HE, hydroxyalkyl is, O-alkyl, O-acyl, S-alkyl, NH2, NH-alkyl, N(alkyl)2, 1-pyrrolidinyl, 1-piperidinyl, 4-morpholinyl, NH-acyl, N(alkyl)-acyl, N3, CO2H, CO2-alkyl, CONH2, CONH-alkyl, CON(alkyl)2CN and CF3;

Ar is selected from a possibly substituted tanila and possibly substituted phenyl;

and is 1 or 2, b is 1, 2 or 3; C is 1 or 2, d is 1, 2 or 3; e is 1, 2, 3 or 4; f is 1, 2 or 3, and g, h, i and j all independently is 1 or 2;

provided that:

not more than one And8And9and10represents NH, N(CH2)dR7or S;

And7and11both are not simultaneously N;

no And7nor And11are not N, if one of the A8And9and10represents NH, N(CH2)dR7or S;

if a10is not-CH=CH-, then one of the A8And9and10represents NH, N(CH2)dR7or S, or one of the A7and11represents N;

not more than one And14And15and16represents NH, N-CH3or S;

And12and13both are not simultaneously N;

if one of the A14And15and16represents NH, N-CH3or S, And12and13both are C; and

one of the A14And15 and16represents NH, N-CH3or S, or one of the A12and13represents N;

for the manufacture of a medicinal product for the treatment of disorders selected from the group consisting of primary dysmenorrhea, premature labor, hypertension, disease Reinhold, brain oedema, motion sickness, small-cell lung cancer, depression, anxiety, hyponatremia, liver cirrhosis and congestive heart failure.

35. The application 34, where at least one of R1, R2and R3represents N and at least one is N.

36. The application 34, where one of R1, R2and R3selected from the group alkyl, O-alkyl, F, Cl and Br, while others are N.

37. The application 34, where X1is NH.

38. The application 34, where a is 1 and b is 2.

39. The application 34, where G1is a group of the General formula 3.

40. The application of 39, where C is 2.

41. The application of 39, where a1represents CH2and2represents NH.

42. The application of 39, where a1represents NH or N-alkyl, and a represents C(=O).

43. The application of 39, where a3represents S, and4and5both represent CH.

44. The application of 39, where a3represents-CH=CH-, and4and5/sup> both represent CH.

45. The application of 39, where a3represents-CH=N-, and4and5both represent CH.

46. The application of 39, where a3represents-CH=CH-, And4represents CH, and5represents N.

47. The application 34, where G1is a group of General formula 6 or 7.

48. Use p, where a3represents S, and4and5both represent CH.

49. Use p, where a3represents-CH=CH-, and4and5both represent CH.

50. Use p, where a3represents-CH=N-, and4and5both represent CH.

51. Use p, where a3represents-CH=CH-, And4represents CH, and5represents N.

52. The application 34, where G1is a group of General formula 4 or 6.

53. The application of paragraph 52, where a6represents NH.

54. The application of paragraph 52, where a8represents NH or N-(CH2)d-R7.

55. The application of item 54, where a9represents N and10represents CH.

56. The application 34, where one of R1, R2and R3selected from the group alkyl, O-alkyl, F, Cl and Br, and the other represents H, and X1represents NH.

57. Application for 34, g is e one of R 1, R2and R3selected from the group alkyl, O-alkyl, F, Cl and Br, and the other represents H, and X1represents NH, and a is 1 and b is 2.

58. The application 34, where G1is a group of General formula 6, And4And5and10all are CH, And6represents NH, And7and11both represent C And8represents N-(CH2)d-R7and9represents N.

59. The application 34, where R1represents a group of alkyl, O-alkyl, F, Cl or Br, R2and R3both represent H, X1represents NH, and a is 1, b is 2, G1is a group of General formula 6, And4And5and10all are CH, And6represents NH, And7and11both represent C And8represents N-(CH2)d-R7and9represents N.

60. The application 34, where the specified connection selected from the group consisting of:

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(3,3-dimethyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(3-methylsulfanyl-propyl)-piperazine-1-carboxylic to the slots 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-hydroxymethyl-cyclopropylmethyl)-piperazine-1-carboxylic acid

2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(3-methyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopentylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclohexylmethyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl the-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-cyclopropyl-ethyl)-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-pentyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-hexyl-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

(R)-4-(2-methyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-ethyl-butyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-(2-methyl-but-2-enyl)-piperazine-1-carboxylic acid 2-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-fluoro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-fluoro-4-(3-methyl-4,10-d the hydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-ethyl-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclobutylmethyl-piperazine-1-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine;

4-cyclopropylmethyl-piperazine-1-carboxylic acid 2-chloro-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine; and

4-cyclobutylmethyl-piperazine-1-carboxylic acid 3-methoxy-4-(3-methyl-4,10-dihydro-3H-2,3,4,9-tetraaza-benzo[f]azulene-9-carbonyl)-benzylamine.



 

Same patents:

FIELD: agriculture.

SUBSTANCE: new chemically biologically active compound 3-amino-4,5,6-trimethyl-2-(benzimidazolyl-2)tieno[2,3-b]pyridine of formula 1 revealing growth regulating properties is described.

EFFECT: increasing sugar beet crop yield and sugar content.

1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted indoles of general formula , where: X stands for -S(O)n-, -C(O)-; A stands for C1-C6alkyl, -(CH2)p-NRaRb; R1, R2, R3 and R4 each is independently selected from group including H, halogen, halogen(C1-C6)alkyl, C1-C6alkyl, C1-C6alkoxy, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, NO2, -NRaRb, phenyl, benzyl and benzyloxy, said phenyl cycles are optionally substituted with substituent, selected from group including C1-C6alkyl, halogen, NO2, halogen(C1-C6)alkyl, C1-C6alkoxy; R5 stands for H, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy C1-C6alkyl, C1-C6alkylthio, C1-C6alkylsulfinyl, C1-C6alkylsulfonyl, hydroxyl-(C1-C6)alkyl, hydroxy(C1-C6)alkylamino, halogen, halogen(C1-C6)alkyl-NRaRb, -NRc-( C1-C6)alkylene-NRaRb, or R5 and A together form radical C2-C3alkylene; R6 stands for H, C1-C6alkyl; R' and R" each independently stand for H, C1-C6alkyl; Ra, Rb and Rc each is independently chosen from group including H, C1-C6alkyl, hydroxy(C1-C6)alkyl, C2-C6alkenyl, C3-C6cycloalkyl-(C1-C6)alkyl, or Ra and Rb together with nitrogen atom, to which they are attached, form 5-7 member non-aromatic heterocyclic cycle, optionally containing in cycle O as additional heteroatom; m is equal 1 or 2; n is equal 0, 1 or 2 under condition that, if n is equal 0, R5 does not stand for NRaRb, and p is equal 0, 1 or 2; or their pharmaceutically acceptable salts.

EFFECT: obtaining compounds possessing agonistic activity which allows using them in pharmaceutical composition.

24 cl, 2 tbl, 22 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to substituted 3-cyanotiophenacetamides of general formula I , in which R1 and R2 are independently designate (lower) alkyl, or R1 and R2 together with carbon atoms, to which they are bound, including bond between said carbon atoms, form 5-6 member, unsubstituted carbocyclic or 6-member heterocyclic cycle, probably having substitutes, independently selected from group, including (lower) alkyl, alkylsulfonyl and alkoxycarbonyl, R3 is selected from group, which includes (lower) alkyl, unsubstituted aryl, unsubstituted aralkyl and unsubstituted cycloalkyl, R4 - hydrogen, n is zero, or their pharmaceutically acceptable salts. Compounds can be applied for treatment and/or prevention of diseases, associated with antagonistic action on glucagon receptor, such as diabetes. Pharmaceutical composition based on compounds I and their application are also described.

EFFECT: obtaining substituted 3-cyanotiophenacetamides, which can be applied for treatment and/or prevention of diseases, associated with antagonistic action on glucagon receptor, such as diabetes.

22 cl, 23 ex

FIELD: chemistry.

SUBSTANCE: invention refers to compounds of formula I their pharmaceutically acceptable salts and solvate I where X represents O or S; Y and Z mutually independently denote hydrogen or halogen; R1 is hydroxy-C1-C7-alkyl, carboxy, C1-C7-alkyloxycarbonyl, or substitute of formula II R2 is hydrogen, carboxy or alkyloxycarbonyl. Compounds can be used as inhibitors of cytokine or inflammation mediator producing. Intermediate compounds of compounds I and application of compounds 1 are also described.

EFFECT: production of compounds used as inhibitors of cytokine or inflammation mediator producing.

12 cl, 1 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: (I) , in which R1 and R2 independently represent C1-6alkyl, C3-5cycloalkyl C1-3alkyl or C3-6dikloalkyl; Q represents CR4R5, where R4 represents hydrogen; or C1-6alkyl, and R5 represents carbon; Ar represents 5-6-membered aromatic ring system, where heteroatoms can represent up to 2 ring atoms, independently selected from nitrogen and sulphur, notably that this ring system can be substituted by one or more then one substitute, independently selected from C1-4alkyl; Ar2 represents 5-6-membered aromatic ring system containing up to 2 ring atoms, independently selected from nitrogen and sulphur, notably the ring contains at least one heteroatom and can be substituted by one or more then one group, independently selected from C1-4alkyl. The compositions can be used in autoimmune disease modulation. The methods of compounds production, pharmaceutical composition and use of the compounds in the treatment of respiratory disease are described.

EFFECT: production of thienopyrimidindion compounds for autoimmune disease modulation and respiratory disease treatment.

14 cl, 3 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to derivatives of thienopyrimidine with general formula I , where R1 represents C1-4alkyl; R2 represents C1-6alkyl, possibly substituted (1') by a hydroxyl group, (2') C1-4alkoxy, (3') C1-4alkoxycarbonyl, (4') di-C1-4alkylcarbamoil, (5') 5-6-member nitrogen containing heterocyclic group, (6') C1-C4alkylcarbonyl and (7') halogen, 5-6-member nitrogen containing heterocyclic group, phenyl, which can contain a substitute, R3 - C1-4alkyl, R4 - C1-4alkoxy. The compounds have antagonist activity to gonadotropin releasing hormones (GnRH). Description is given of a medicinal preparation based on formula I compounds, used of the compounds in making pharmaceutical compositions and the antagonist effect of the compounds on gonadotropin releasing hormone.

EFFECT: obtaining derivatives of thienopyrimidine with antagonist effect on gonadotropin releasing hormones.

17 cl, 143 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to thienopyrimidine diones with general formula (I), , where R1 and R2 each independently represents C1-6alkyl, C3-5cycloalkylC1-3alkyl or C3-6cycloalkyl; R3 represents a CO-G group, where G is a 5- or 6-member ring, containing a nitrogen atom and a second oxygen heteroatom, adjacent to the nitrogen atom. This ring can be substituted by at least one group, chosen from C1-4alkyl and hydroxyl; Q represents CR4R5, where R4 represents hydrogen or C1-6alkyl, and R5 represents hydrogen; and Ar represents a 5-10-member aromatic ring system, where up to 3 ring atoms can represent heteroatoms, independently chosen from nitrogen and sulphur. This ring system can be substituted with one or more groups. The invention also relates to pharmaceutical salts and solvates of thienopyrimidine diones. Description is also given of the method of obtaining these compounds, pharmaceutical compositions containing them, and their use in therapy, particularly in immunosuppressive therapy.

EFFECT: obtaining thienopyrimidine diones for use in immunosuppressive therapy.

17 cl, 29 ex

New compounds // 2331646

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to thienopyridazinones with formula , where R1 represents C1-6alkyl, or C3-6cycloalkyl, R2 represents C1-6alkyl; R3 represents a CO-G group, where G is a 5-member ring, containing a nitrogen atom and a second heteroatom, chosen from oxygen, adjacent to the nitrogen atom, and can be substituted with groups in quantity of up to 2, chosen from hydroxyl and C1-4alkyl; Q represents CR5R6, where R5 and R6 - hydrogen, and R4 represents a 5-10-member mono- or bi-cyclic aromatic ring system, containing 2 heteroatoms, independently chosen from nitrogen. This ring system can be substituted. The invention also relates to pharmaceutical salts and solvates of thienopyridazinones. Description is also given of the method of obtaining these compounds, pharmaceutical compositions containing them, and their use in therapy, particularly in the modulation of autoimmune disease.

EFFECT: obtaining thienopyridazinones for use in modulation of autoimmune disease.

12 cl, 17 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the novel form of the crystalline clopidogrel naphthalenesulfonate with formula Ia: for which the powder X-ray diffraction scanning reveals the principal peaks with the I/I0 values more than 10% at 2θ=6.7, 8.2, 8.5, 12.4, 13.0, 13.5, 16.8, 17.2, 18.9, 19.6, 20.2, 21.2, 22.3, 22.9, 23.2, 23.6, 24.7, 25.0, 25.3, 25.8, 27.0, 27.5, 28.0, 28.6, 32.1, 32.5, 34.7. and monohydrate crystalline clopidogrel 1,5-naphthalenesulfonate with formula (Ib) for which the powder X-ray diffraction scanning reveals the principal peaks with the I/I0 values more than 10% at 2θ=7.6, 9.7, 10.7, 11.0, 12.1, 13.6, 14.2, 15.3, 16.6, 17.0, 18.1, 18.5, 19.8, 21.5, 22.2, 23.0, 23.5, 24.3, 24.8, 25.7, 26.4, 26.9, 27.3, 28.4, 29.0, as well as to the method of their production and to their pharmaceutical composition.

EFFECT: increased stability of compounds.

10 cl, 8 dwg, 9 tbl, 4 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the novel compounds with the formula (I) or their pharmaceutically or veterinary-acceptable salts: where: R1 and R3 independently represent H; F; Cl; Br; C1-C6alkyl; R2 represents H or C3-C7cycloalkyl; Y represents -S- or -N(R5)-, where R5 represents H; X represents the bind; R4 represents -C(=O)NR6R7, where R6 represents H or radical of formula -(Alk)b-Q, where b is equal to 0 or 1, and Alk is not necessarily substituted with C1-C6alkyl, C1-C6alkoxi, F, Cl, Br, oxo, COOH, bivalent C1-C12alkylen, C2-C12alkenylen with direct or ramified chain, which can be disconnected with one ore several non-adjacent -O-, -S- or -N(R8)-, where R8 represents H or C1-C4alkyl, C3-C4alkenyl or C3-C6cycloalkyl, and Q represents H; -SH; -NR8R8, where each R8 can be similar or different; the complex ether group; or not necessarily substituted with C1-C6alkyl, C1-C6alkoxi, phenyl, benzyl, phenoxy, C3-C8cycloalkyl, amino, fluor, bromine, oxo, -COOH, -CORA, -COORA, NHRA, -NRARB, where RA and RB are independent (C1-C6)alkyl group, phenyl, C3-C7cycloalkyl, C5-C7cycloalkenyl or heterocyclilc ring containing 5 to 8 ring atoms; and R7 represents H or C1-C6alkyl; or, taken together with atom or atoms, they are bound with, R6 and R7 form not necessarily substituted with (C1-C6)alkyl, COORA, where RA is the (C1-C6)alkyl group, phenyl, not necessarily substituted with F, Cl, Br, heterocyclilc ring containing 5 to 8 ring atoms. The invention also relates to N-(3-dimethylaminopropyl)-4-(4-cyclopropyl-3-oxo-3,5-dihydropirazol[4,3-c]quinoline-2-il]benzamide; to application of the compounds; to the immunomodulation method and to the pharmaceutical and veterinary composition.

EFFECT: production of novel immunobiologic compounds.

14 cl, 173 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: 2-R-4-(allyloxymethyl)-6-nitro-1,2,4-triazolo [5,1-c]-1,2,4-triazin-7(4H)-ons of general formula (1) and 2-R-4-(propargyloxymethyl)-6-nitro-1,2,4-triasolo[5,1-c]-1,2,4-triazin-7(4H)-ons of general formula (2) .

EFFECT: anti-viral activity of compound.

1 cl, 3 tbl, 5 ex, 2 dwg

FIELD: chemistry.

SUBSTANCE: in general formula I

R1 is phenyl or 5-6-member heterocycle, containing one N atom and/or one O atom; R2 is imidazole or annelated imidazole, selected from group, including a), b), c), d) and e); and R3 stands for hydrogen, phenyl, 2,3-dihydrobenzo[1,4]dioxin-6-yl, benzo[b]thiophen-3-yl, 3-methylbenzo[b] thiophen-2-yl, thiophen-2-yl or thiophen-2-ylmethyl, R4 is hydrogen or lower alkyl, R5 is hydrogen, lower alkyl, halogen, morpholinyl, -NR'R", piperydinyl, optionally substituted with hydroxy-group, or is pyrrolidin-1-yl; R6 is hydrogen or -(CH2)nO-lower alkyl, R7 is hydrogen, -C(O)O-lower alkyl, -C(O)-C6H4-halogen, -C(O)-C6H4-lower alkyl, -C(O)-lower alkyl, -C(O)-cycloalkyl, -C(O)-NR'R", -C(O)-(CH2)nO-lower alkyl, -S(O)2-lower alkyl, -(CH2)nO-lower alkyl, -C(O)-pyridin-4-yl, whose ring can contain as substituents lower alkyl, halogen-lower alkyl or pyrrolidin-1-ylmethyl or is -(CH2)n-C(O)-NR'R"; R'/R" independently on each other stand for hydrogen, lower alkyl or -(CH2)n-tetrahydropyran-4-yl, X is -CH2-, -NR'''- or -O-; R''' is hydrogen, -C(O)-lower alkyl, -C(O)O-lower alkyl, -C(O)-C6H4CH3 or benzyl; n is 1 or 2.

EFFECT: increase of composition and treatment method efficiency.

14 cl, 56 ex

FIELD: chemistry.

SUBSTANCE: claimed are novel pyrazole derivatives of formula II or its pharmaceutically acceptable salts, where C ring is selected from phenyl or pyridinyl ring and R2, R2', Rx and Ry are such as said in given description. C ring has ortho-substituent and is optionally substituted in non-ortho positions. R2 and R2' , optionally taken with their intermediate atoms, form condensed ring system, such s indazole ring, and Rx and Ry, optionally taken together with their intermediate atoms, form condensed ring system, such a quinazoline ring.

EFFECT: possibility to use compositions as inhibitors of protein kinases as inhibitors GSK-3 and other kinases and apply them for protein kinase-mediated diseases.

41 cl, 8 tbl, 423 ex

FIELD: medicine.

SUBSTANCE: new derivatives of pyrrol[2,1-c][1,4]benzodiazepine of the general formula where n=2-10 are described. A pharmaceutical composition, containing them, and the method of obtaining are also described.

EFFECT: compounds possess antitumoral activity and can be applied in medicine.

18 cl, 3 ex, 2 tbl, 1 dwg

FIELD: chemistry.

SUBSTANCE: claimed invention relates to pyperidine derivatives of formula (I) , where R represents galogen or C1-4alkyl; R1 represents C1-4alkyl; R2 or R3 independently represent hydrogen or C1-4alkyl; R4 represents trifluorinemethyl or galogen; R5 represents hydrogen, C1-4alkyl or C3-7cycloalkyl; R6 represents hydrogen, R7 represents radical of formula (W), or R7 represents radical of formula (W) and R7 represents hydrogen; X represents CH2, NR5 or O; Y represents nitrogen, and Z represents nitrogen; or Y represents CH, and Z represents nitrogen; A represents C(O), m is zero or whole number from 1 to 3; t is whole number from 1 to 3; and p and q are whole number from 1 to 2; or to their pharmaceutically acceptable salts and solvates. Claimed invention also relates to method of obtaining said derivatives and to their application for treating condition with tachyquininamia.

EFFECT: obtaining pyperidine derivatives, which can be used for treating tachyquininamia.

14 cl, 29 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine derivatives of formula I and their pharmaceutically acceptable salts, which are selective inhibitors of kinases KDR, FGFR and PDGFR and can be used for treatment of oncological diseases. Compound of formula I corresponds to structural formula , where R1 is selected from group, including H, COR4 and COOCHR5OCOR4; R2 and R3 are independently selected from group, including C1-6alkyl, C1-6alkyl, substituted with not more than 4 groups, which are independently selected from group, including -NR5R6,-R5, -OR5-phenyl,-phenyl, substituted with not more than 2 groups, which are independently selected from group, including OR5 and -C1-4alkyl and heteroaryl, representing aromatic heterocyclic ring system, which contains not more than two rings and includes from 1 to 3 nitrogen atoms, and heterocyclyl, representing saturated cyclic radical, which includes from 1 to 3 nitrogen atoms; R5 and R6 are independently selected from group H and C1-5alkyl. Invention also relates to pharmaceutical compositions, containing said compounds of formula I and intermediate products.

EFFECT: obtaining new pyrimidine derivatives, which can be used for treating oncological diseases.

17 cl, 2 tbl, 27 ex

FIELD: agriculture.

SUBSTANCE: description is given to fungicide based on triazolpyrimidine derivatives with general formula of I , R1 - is possibly substituted by haloid C1-8alkyl or C3-6cycloalkyl possibly substituted by C1-6alkyl; R2 stands for hydrogen or C1-8alkyl; or R1 and R2, together with nitrogen atom to which they are bound, form 5-7-membered N-containing heterocyclic ring, possibly substituted by C1-6alkyl; R3 - phenyl substituted by haloid, C1-6alkyl, C1-6alkoxy or simultaneously by haloid and C1-6alkoxy; R4 - haloid for preserving wood from basidiomycetes destroying it, and to the method of preservation wood and woody materials.

EFFECT: producing substance for effective preservation of wood and woody materials.

2 cl

FIELD: chemistry.

SUBSTANCE: invention describes new heterocyclic compounds of the general formula I where A is -(CH)-, -N- or -CH2-N-; B is -(CH2)-, -(CH2-CH2)-; D is -(CH2)- or -(C=O)-; W is -(C=O)- or is absent; X is -NH(C=O)- or is absent; Y is oxygen or sulfur; L is hydrogen, -C(O)NHR3 or -C(=O)OR4; R1 is C1-12alkyl; C6-10aryl; C1-6alkoxy; C6-10aralkyl; C6-10aralkyloxy; R2 is saturated or non saturated C1-10alkyl, possibly substituted; C1-10alkenyl; C6-10aralkyloxy; C1-10alkanedienyl; C6-10aryl, possibly substituted; C6-10aralkyl, possibly substituted; benzodioxolyl; piperonyl; chromenonyl; alkyl-C(=O)-; 5-6-membered heteroaryl with one or two nitrogen atoms, or oxygen atom, or sulfur atom, and possibly substituted; R3 is a radical of the formula or benzene; where Ra is C1-10alkyl, possibly substituted; C1-10alkenyl; C3-10cycloalkyl; amino; C6-10aralkyl; possibly substituted; Rd is hydrogen; C6-10aralkyl, possibly substituted; R4 is C6-10aralkyl; on the condition that if A is -(CH)- then B is -(CH2)-, D is -(CH2)-, X is -NH(C=O)- and L is -C(=O)NHR3; if A is N then B is -(CH2-CH2)- and X is absent; if A is -CH2-N- then B is -(CH2)-, D is -(CH2)-, W is -(C=O)-, X is absent and L is hydrogen; the invention also describes a pharmaceutical composition containing the claimed compounds.

EFFECT: obtaining compound with NF-kB transcription inhibition effect, applicable in medicine.

7 cl, 3 tbl, 10 ex, 4 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to the new compounds of formula I which can be used in photopolymer composition hardening with catalyst, possible during rays, and as photoinitiators for coating preparation. In formulas (I) and (II) $ , in which R1 denotes phenyl, naphthyl, phenanthryl, anthryl, pyrenil 5,6,7,8-tetrahydro-2-naphthyl,5,6,7,8-tetrahydro-1-naphthyl, thienyl, tiantrenyl, anthraquinonyl, xantenyl, thioxantyl, phenoxantyinyl, carbazol, phenantridinyl, akridinyl, fluorenyl or phenoxazinyl, besides radicals is unsubstituted or once or several times substituted by C1-C18alkyl, C2-C18alkenyl, C1-C18haloalkyl, NO2, NR10R11, CN, OR12, SR12, halogen atom or radical of formula II or radical R1 denotes radical of formula III . R2 and R3 independently denote a hydrogen atom; R10, R11 R12 independently denote a hydrogen atom or C1-C18alkyl; R4 and R6 form C2-C12alkylen bridge, which is not substituted or substituted by or several C1-C4alkyl radicals; R15 denotes H or radical of formula II.

EFFECT: production of the nitrogen bases that can be used as a photopolymer composition, hardening with catalyst, and as photoinitiator for coating.

11 cl, 4 tbl, 21 ex

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to new compounds with formula I, their pharmaceutical salts and to complex esters. The invented compounds have inhibiting propertied towards catepsin K and can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved, for example, inflammation, rheumatoid arthritis, osteoarthritis, osteoporosis and tumorous diseases. In general formula I R represents H, R13 represents (inferior)alkyl, C3-C10cylcloalkyl or C3-C10cycloalkyl(inferior)alkyl, each of which is independently optionally substituted with a halogen atom, hydroxyl, CN, NO2 or optionally mono- or di(inferior)alkyl substituted amino group; and R14 represents H or optionally substituted phenyl, phenyl-W-, phenyl(inferior)alkyl-W-, C3-C10cycloalkyl, C3-C10cycloalkyl-W-, N-heterocyclyl, N-heterocyclyl -W-. Substitutes of the indicated values of radicals are shown in the formula of invention. The invention also relates to methods of obtaining the compounds.

EFFECT: obtaining pyrrolopyrimidines with inhibiting properties towards catepsin K, which can be used for making medicinal preparations for curing diseases and conditions, in which catepsin K is involved.

4 cl, 59 tbl, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the novel compounds with the common formula III: where, if X is selected from the group containing NH and S, R1, R2, R3, R4, R5, R6, R7, R8 and R9, each independently is selected from the group containing H, OH, OR', substituted or unsubstituted aryl, where substitutes independently correspond to H, OH, C1-C12alkoxy; where, if X means O, R1, R2, R3, R4, R5, R6, R7 and R8, each independently, selected from the group containing H, OH, OR', SH, SR', SOR', SO2R', OSO2R', NHR', N(R') CO2R', OC(=O)R'; and R9 independently selected from the group containing H, OR', unsubstituted or substituted with aminogroup or halogen C2-C12 alkenyl, unsubstituted C2- C12 alkenyl, unsubstituted thienyl and halogen; where each of the R' groups are independently selected from the group containing H, substituted or unsubstituted C1-C18 alkyl, substituted or unsubstituted aryl; where substitutes are independently selected from the group containing halogen, OH, CN, C1-C12 alkoxy, phenyl; and the dotted line represents the simple or double bind; or its pharmaceutically compatible salt or complex ether. Other novel lamellarin analogs are described.

EFFECT: compounds have antitumor activity.

24 cl, 2 tbl, 3 ex

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