Diazacycloalkanes as oxytocin agonists

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to diazacycloalkanes of the general formula (I): wherein G1 represents condensed polycyclic group. Compounds are selective and strong acting agonists of oxytocin and can useful in treatment of erectile dysfunction. Also, invention describes a pharmaceutical composition based on compounds of the formula (I) and their using in manufacturing the pharmaceutical composition.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

31 cl, 136 ex

 

The text descriptions are listed in facimile.

1. The compound of General formula 1 or its pharmaceutically acceptable salt

where G1selected from the group of the 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 CH2, NH and N-alkyl;

And2selected from CH2and NH;

And3

And4and5each selected from CH and N;

And6selected from CH2, NH, N-alkyl and Oh;

And7and11selected from C and N;

And8and9selected from CH, N, NH, N(CH2)dR7and S;

And10selected from-CH=CH-, CH, N, NH, N(CH2)dR7and S;

And12and13selected from N and C;

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

X1selected from O and NH;

R1, R2and R3each selected from H, alkyl, F, Cl and Br;

R4selected from H, alkyl, alkenyl, quinil, possibly substituted phenyl, possibly substituted tanila, possibly substituted Furie, possibly substituted pyridyl, -(CO)-O-(CH2)eR8, -(CH2)eR8, -CH2-CH=CH-CH2-R8, -CH2-C≡C-CH2-R8, -(CH2)g-CH(OH)-(CH2)h-R8, -(CH2)i-O-(CH2)j-R8and

R7selected from H, alkyl and phenyl;

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 samewe the aqueous imidazole, 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, CONH3, CONH-alkyl, CON(alkyl)2CN and CF3;

and equal to 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; 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 represent N;

no And7nor And11not represent N, if one of the A8And9and10represents NH, N(CH2)dR7or S;

if a10represents-CH=CH-, then A8represents N And9represents CH, and both And7and11represent;

if a10does not represent a-CH=CH-, then one of the A8And9and10represents NH, N(CH2)dR7or S, or one And7and11represents N;

not more than one And14And15and16not only is em a NH, N-CH3or S;

And12and13both are not simultaneously represent N;

if one of the A14And15and16represents NH, N-CH3or S, then A12and13both are C; and

one of the A14And15and16represents NH, N-CH3or S, or one And12and13represents N.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, where at least one of R1, R2and R3represents H, and at least one is not an N.

3. The compound according to claim 1 or 2, or its pharmaceutically acceptable salt, where one of R1, R2and R3selected from alkyl groups, F, Cl and Br, and the remaining represent N.

4. The compound according to claim 1 or its pharmaceutically acceptable salt, where R1selected from a methyl group and Cl, and R2and R3represent N.

5. The compound according to claim 1 or its pharmaceutically acceptable salt, where X1represents NH.

6. The compound according to claim 1 or its pharmaceutically acceptable salt, where a equals 1 and b equals 2.

7. The compound according to claim 1 or its pharmaceutically acceptable salt, where G1represents a group of General formula 3.

8. The connection according to claim 7 or its pharmaceutically acceptable salt, where C is equal to 2.

9. The connection according to claim 7 or f is rmaceuticals acceptable salt, where a1represents CH2and2represents NH.

10. The connection according to claim 7 or its pharmaceutically acceptable salt, where a3represents S, and4and5both represent CH.

11. The connection according to claim 7 or its pharmaceutically acceptable salt, where a3represents-CH=CH-, and4and5both represent CH.

12. The connection according to claim 7 or its pharmaceutically acceptable salt, where a3represents-CH=N-, and4and5both represent CH.

13. The connection according to claim 7 or its pharmaceutically acceptable salt, where a3represents-CH=CH-, And4represents CH, and5represents N.

14. The compound according to claim 1 or its pharmaceutically acceptable salt, where G1represents a group of General formula 6 or 7.

15. The connection 14 or its pharmaceutically acceptable salt, where a3represents S, and4and5both represent CH.

16. The connection 14 or its pharmaceutically acceptable salt, where a3represents-CH=CH-, and4and5both represent CH.

17. The connection 14 or its pharmaceutically acceptable salt, where a3represents-CH=N-, and4and5both represent CH.

18. The connection 14 or headlamp is asepticheski acceptable salt, where a3represents-CH=CH-, And4represents CH, and5represents N.

19. The compound according to claim 1 or its pharmaceutically acceptable salt, where G1represents a group of General formula 4 or 6.

20. The connection according to claim 19 or its pharmaceutically acceptable salt, where a6represents NH.

21. The connection according to claim 19 or its pharmaceutically acceptable salt, where a8represents NH or N-(CH2)d-R7.

22. Connection item 21 or its pharmaceutically acceptable salt, where a9represents N and10represents CH.

23. The compound according to claim 1 or its pharmaceutically acceptable salt, where R1represents methyl or Cl, R2and R3both represent H, and X1represents NH.

24. The compound according to claim 1 or 23, or its pharmaceutically acceptable salt, where R1represents methyl or Cl, R2and R3both represent H, X1represents NH, a is 1 and b is 2.

25. The compound according to claim 1 or its pharmaceutically acceptable salt, where G' represents a group of General formula 6, And4And5and10all are CH, And6represents NH, And7and11both represent C And8represents N-(CH2)d-R7and9pre is is a n

26. The compound according to claim 1 or its pharmaceutically acceptable salt, where R1represents methyl or Cl, R2and R3both represent H, X1represents NH, 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.

27. The compound according to claim 1, selected from

5-(4-(4-cyclopropylamines-1-carbonylmethyl)-3-methyl-benzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

5-(4-(4-benzylpiperazine-1-carbonylmethyl)-3-methyl-benzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

5-(4-(4-(3-hydroxybenzyl)piperazine-1-carbonylmethyl)-3-methyl-benzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

5-(4-(4-(3-hydroxymethylene)piperazine-1-carbonylmethyl)-3-methylbenzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

1-methyl-5-(3-methyl-4-(4-(4-picolyl)piperazine-1-carbonylmethyl)-benzoyl)-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

5-(4-(4-(2-hydroxyethyl)piperazine-1-carbonylmethyl)-3-methyl-benzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

1-methyl-5-(3-methyl-4-(4-(3-(methylthio)about who yl)piperazine-1-carbonyl-aminomethyl)benzoyl)-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

5-(4-(4-(2-amino-ethyl)piperazine-1-carbonylmethyl)-3-methyl-benzoyl)-1-methyl-4,10-dihydropyrazolo[5,4-b][1,5]benzodiazepine

5-(4-(4-(2-hydroxyethyl)piperazine-1-carbonylmethyl)-3-methyl-benzoyl)-1-methyl-4,10-dihydropyrazolo[4,5-C]pyrido[2,3-b][1,4]diazepine

and their pharmaceutically acceptable salts.

28. Pharmaceutical composition having activity of oxytocin agonist containing a compound or salt according to any one of claims 1 to 27 as the active agent.

29. The pharmaceutical composition according p, which is a tablet or capsule for oral administration.

30. The use of compound or salt according to any one of claims 1 to 27 in the manufacture of a pharmaceutical composition having agonist activity of oxytocin.

31. The pharmaceutical composition according p or 29 or the application of article 30, where the pharmaceutical composition is intended for the treatment of male erectile dysfunction and/or other male sexual disorder or female sexual disorders.



 

Same patents:

FIELD: organic chemistry, pharmaceuticals.

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EFFECT: new oxytocin antagonists.

30 cl, 177 ex

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7 cl, 105 ex

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15 cl, 1 dwg, 4 tbl, 5 ex

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36 cl, 1 dwg, 16 tbl, 131 ex

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11 cl, 5 sch, 1 tbl

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6 cl, 1 tbl, 7 ex

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14 cl, 44 ex

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EFFECT: valuable biological and medicinal properties of compounds.

11 cl, 1 tbl, 27 ex

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EFFECT: improved method of synthesis, valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 1 tbl, 39 ex

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EFFECT: stimulation of sunflower seed germination; increased sunflower productivity.

2 tbl, 3 ex

FIELD: organic chemistry, medicine.

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EFFECT: valuable medicinal properties of compounds.

6 tbl, 1 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

7 cl, 6 ex

FIELD: organic chemistry, pharmaceuticals.

SUBSTANCE: invention relates to compounds of general formula 1 (G1 is group of general formulae 2 G1 is group of general formulae ; meanings of the rest substituents are as described in specification) or pharmaceutically acceptable salts thereof and use thereof in srug production. Said compounds are useful in treatment of male and female sexual disorders.

EFFECT: new oxytocin antagonists.

30 cl, 177 ex

FIELD: organic chemistry.

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23 cl, 5 tbl, 52 ex, 6 dwg

FIELD: organic chemistry, drugs.

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7 cl, 17 tbl, 17 ex

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9 cl, 134 ex

FIELD: organic chemistry, medicine, pharmacy.

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EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions, improved preparing method.

15 cl, 1 dwg, 4 tbl, 5 ex

FIELD: organic chemistry, biochemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and their pharmaceutically acceptable salts possessing properties of inhibitors of protein kinase p38. In the formula (I) A means nitrogen atom (N) or -CH; R1 means hydrogen atom, alkyl or aralkyl; R2 means (C1-C6)-alkyl, hydroxy-(C1-C6)-alkyl, (R'')2NCO-alkylene- (wherein each R'' means independently hydrogen atom or (C1-C6)-alkyl), (C3-C7)-cycloalkyl substituted optionally with hydroxy-group, 6-membered heterocyclyl comprising nitrogen, oxygen or sulfur atom or its oxides as heteroatoms and wherein nitrogen-containing heterocyclyl can be substituted with (C1-C4)-alkylsulfonyl group, optionally substituted phenyl wherein substitutes are chosen from halogen atoms and lower alkoxy-group; X means oxygen atom (O), -NR3 or sulfur atom (S) wherein R3 means (C1-C6)-alkyl or phenyl; Y means a chemical bond, O, C(=O), -CH(OR'), -CHR' or S wherein R' means hydrogen atom; R means phenyl optionally substituted with one or some substitutes chosen from halogen atoms, lower alkyl and lower alkoxy-group. Proposed compounds can be used, for example, in treatment of inflammatory diseases, among them intestine disease, Alzheimer's disease, Crohn's disease, cerebrospinal sclerosis, asthma and can be used in development of viral diseases also.

EFFECT: valuable medicinal properties of compounds.

11 cl, 5 sch, 1 tbl

FIELD: organic chemistry, medicine, hepatology.

SUBSTANCE: invention relates to using 2-methylthiopyrimido[4,5-b]indole of the formula (1): showing melting point at 243°C (with decomposition) and value LD50 > 1000 mg/kg used in liver protection from poisoning with carbon tetrachloride. Proposed compound exceeds activity of the "Essentiale" as a comparison preparation.

EFFECT: valuable medicinal property of compound, enhanced effectiveness.

1 tbl

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): possessing properties of inhibitor of inflammatory cytokines release from cells. In compound of the formula (I) R is chosen from: (a) fragment of the formula -OR3 wherein R3 is chosen from group consisting of phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,6-difluorophenyl, 2-cyanophenyl, 3-cyanophenyl, 2-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-methylphenyl, 4-methylphenyl, 2,4-dimethylphenyl, 3-N-acetylaminophenyl, 2-methoxyphenyl, 4-methoxyphenyl and 3-benzo[1,3]dioxol-5-yl; (b) fragment of the formula: wherein R6 is chosen from group consisting of hydrogen atom, methyl, ethyl, vinyl, cyclopropyl, cyclohexyl, methoxymethyl, methoxyethyl, 1-hydroxy-1-methylethyl, carboxy-group, 4-fluorophenyl, 2-aminophenyl, 2-methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-(propanesulfonyl)phenyl, 3-benzo[1,3]dioxol-5-yl, pyridine-2-yl, pyridine-3-yl, or (c) fragment of the formula: wherein R6 is chosen from group consisting of hydrogen atom, methyl, ethyl, vinyl, cyclopropyl, cyclohexyl, methoxymethyl, methoxyethyl, 1-hydroxy-1-methylethyl, carboxy-group, phenyl, 4-fluorophenyl, 2-aminophenyl, 2-methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-(propanesulfonyl)phenyl, 3-benzo[1,3]dioxol-5-yl, pyridine-2-yl, pyridine-3-yl; each radical R2 is chosen independently from group consisting of (a) hydrogen atom; (b) -(CH2)jO(CH2)nR8; (c) -(CH2)jNR9aR9b; (e) -(CH2)OCO2R10; (g) -(CH2)jOCON(R10)2 wherein each radical R8, R9a, R9b and R10 represents independently hydrogen atom, (C1-C4)-alkyl; or R9a and R9b can form in common 5-6-membered heterocyclic ring comprising 1-2 heteroatoms chosen from nitrogen and/or oxygen atoms; or two radicals R10 can form in common 5-6-membered heterocyclic ring comprising 1-2 heteroatoms chosen from nitrogen and/or oxygen atoms; j represents index 0; n represents index 0. Also, invention relates to a pharmaceutical composition and a method for inhibition.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

15 cl, 2 sch, 8 tbl, 13 ex

FIELD: medicine, urology, sexopathology.

SUBSTANCE: about 4-5 wk after the trauma it is necessary to introduce Impaza for a patient per 1 tablet before meals in the morning during 1-2 month every other day. Then during 5-6 month additionally during the days between Impaza intake it is necessary to introduce Levitra at the dosage of 5 mg after meals in the morning twice or thrice weekly. Then Levitra intake should be stopped to continue Impaza intake for 1-2 mo more. Due to the scheme of stage-by-stage introduction of medicinal preparations the innovation prevent the hemorrhage out of traumatic areas and, also, the development of ischemia and fibrosis of cavernous bodies at early stages after urethral trauma.

EFFECT: higher efficiency of therapy.

6 dwg, 2 ex

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