New derivatives of pyridazin-3(2h)-one

FIELD: chemistry.

SUBSTANCE: invention claims derivatives of pyridazin-3(2H)-one of formula (I), where R1, R2 and R4 are organic radicals described in the claim 1, R3 is cyclic group described in the claim, and R5 is phenyl or heteroaryl group described in the claim. Compounds of formula (I) inhibit phosphodiesterase 4 (PDE-4) and can be applied in treatment of various diseases or pathological states alleviated by PDE-4 inhibition, and in medicine production for treatment of aforesaid diseases. Also invention claims method of obtaining these compounds and intermediate compounds for their obtainment.

EFFECT: obtaining compounds which can be used in treatment of various diseases or pathological states and in medicine production for treatment of aforesaid diseases.

25 cl, 28 tbl, 243 ex

 

The text descriptions are given in facsimile form.

1. Derived pyridazin-3(2H)-she formulas (I)

in which R1means

With1-6alkyl group, optionally substituted hydroxy,

or a group of the formula -(CH2)n-R6in which n denotes an integer from 0 to 4 and R6stands With3-6cycloalkyl group;

R2means

a hydrogen atom, a C1-6alkyl group or a phenyl group which is substituted by 1-2 substituents selected from halogen atoms, hydroxy-C1-6alkyl groups, CO2(C1-4)alkyl groups, nitro - or cyanopropyl;

R3denotes a monocyclic or bicyclic6-10aryl or 5-14 membered monocyclic or polycyclic heteroaryl group containing from 1 to 3 heteroatoms selected from N, O and S, which optionally contains one or more substituents selected from the

atomo is halogen;

C1-6alkyl group which is optionally substituted by a Deputy selected from hydroxy, hydroxycarbonyl,1-6alkoxycarbonyl group;

phenyl, hydroxy, hydroxy-C1-6of alkyl, C1-6alkoxy, nitro, amino, mono - or di(C1-6)alkylamino, hydroxycarbonyl, C1-6alkoxy-carbonyl, carbamoyl, mono - or dialkyl(C1-6)carbamoyl and cyanopropyl;

R5denotes phenyl or monocyclic or bicyclic 5-to 10-membered heteroaryl group, containing 1 to 3 heteroatoms selected from N, O and S, which is optionally substituted by one or more substituents selected from the

atoms of halogen,

With1-6alkyl groups,

With1-6alkoxy, C1-6alkylthio, hydroxycarbonyl or1-6alkoxycarbonyl group;

R4means

With1-6alkyl group, optionally substituted hydroxy-group,

or a group of the formula - (CH2)n-R6in which n has the meanings given above, R6denotes phenyl, thienyl or pyridyloxy group;

and N-oxides derived from heteroaryl radicals contained in the structure, if these heterarchical contain N atoms, and their pharmaceutically acceptable salt,

provided that if R5not putting the AET optionally substituted heteroaryl group, R3denotes optionally substituted heteroaryl group.

2. The compound according to claim 1, in which R2denotes a hydrogen atom or a phenyl group which optionally is substituted by 1-2 substituents selected from halogen atoms, nitro, hydroxy(C1-C4)alkyl or CO2-(C1-C4alkyl) groups.

3. The compound according to claim 2, in which R2denotes a hydrogen atom or a phenyl group which is unsubstituted or contains 1 or 2 unsubstituted substituent selected from fluorine atoms or chlorine and nitro, hydroxy(C1-C4)alkyl or-CO2-(C1-C2alkyl) groups.

4. The compound according to claim 1, in which R1denotes a group selected from C1-C4alkyl group, optionally substituted hydroxy-group; and

group of the formula - (CH2)n-R6in which n denotes an integer from 1 to 3, and R6means (C3-C6)cycloalkyl group.

5. The compound according to claim 4, in which R1denotes unsubstituted With1-C4alkyl, unsubstituted With1-C4hydroxyalkyl, or unsubstituted cyclopropyl-(C1-C4alkyl) group.

6. The compound according to claim 1, in which R3denotes a monocyclic or bicyclic6-10aryl or 5-14 membered monocyclic or alicyclics heteroaryl group, containing from 1 to 3 heteroatoms selected from N, O and S, which optionally contains one or more substituents selected from the

atoms of halogen;

With1-4alkyl group, optionally substituted hydroxy-group; and

With1-4alkoxy, nitro, hydroxy, hydroxycarbonyl, carbamoyl,1-4alkoxycarbonyl or ceanography.

7. The connection according to claim 6, in which R3denotes a phenyl group, naftalina group or a 5-14-membered monocyclic or polycyclic heteroaryl group containing 1, 2 or 3 heteroatoms selected from N, O and S, where phenyl, naftalina and heteroaryl groups are unsubstituted or substituted by 1 or 2 unsubstituted substituents selected from the

atoms of halogen;

With1-4alkyl groups and C1-4hydroxyalkyl group; and

With1-4alkoxy, nitro, hydroxy, hydroxycarbonyl, carbamoyl,1-4alkoxycarbonyl and ceanography.

8. The connection according to claim 7, in which R3denotes a phenyl group, naftalina group, or substituted or unsubstituted heteroaryl group selected from substituted or unsubstituted oxadiazolyl, oxazolidines, peredelnoj, pyrrolidino, imidazolidine, thiazolidine, thiadiazolyl, thienyl, fernilee, hyalinella, ethanolamines, indolines, benzac soleley, naphthyridinone, benzofuranyl, personalni, pyrimidinyl and various pyrrolopyridine radicals.

9. The compound according to claim 1, in which R4denotes an alkyl group containing from 1 to 6 carbon atoms and which is optionally substituted by a hydroxyl group.

10. The compound according to claim 1, in which R5denotes a phenyl group or a monocyclic or bicyclic 5-to 10-membered heteroaryl group, containing 1 to 3 heteroatoms selected from N, O and S, which is optionally substituted by one or more substituents selected from halogen atoms, With1-4alkyl group, a C1-4alkoxycarbonyl group, hydroxycarbonyl and C1-4alkoxygroup.

11. The connection of claim 10, in which R5denotes a phenyl group or a monocyclic or bicyclic 5-to 10-membered heteroaryl group, containing 1 to 3 heteroatoms selected from N, O and S, which is optionally substituted by one or more substituents selected from halogen atoms, With1-4alkoxygroup.

12. Connection by claim 11, in which R5denotes a phenyl group or a 5-10-membered monocyclic or bicyclic heteroaryl group containing 1 or 2 heteroatoms selected from N, O and S, where phenyl and heteroaryl groups are unsubstituted or substituted by 1 or 2 substituents selected and the 1-4alkoxygroup and halogen atoms, e.g. chlorine atoms and fluorine.

13. The connection section 12, in which R5denotes a phenyl group or substituted or unsubstituted heteroaryl group selected from substituted or unsubstituted oxadiazolyl, oxazolidines, peredelnoj, pyrrolidino, imidazolidine, thiazolidine, thiadiazolyl, thienyl, fernilee, hyalinella, ethanolamines, indolines, benzoxazolyl, naphthyridinone, benzofuranyl, personalni, pyrimidinyl and various pyrrolopyridine radicals.

14. The connection of claim 1, wherein, if R5denotes a bicyclic heteroaryl group, then it represents a group of formula (XXIII)

in which Y denotes an atom, S atom or-NH-group, n is 0, 1 or 2 and all R are identical or different and denote With1-C4alkoxygroup or halogen atom.

15. The compound according to any preceding paragraph, which is one of the following:

5-acetyl-2-ethyl-4-[(3-forfinal)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-3-ileribasi-3 (2H)-he

5-acetyl-4-[(3,5-dichlorophenyl)amino]-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(1-naphthylamine)-6-pyridin-3-ileribasi-3(2H)-he

methyl-4-[(5-Aza the Il-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridin-4-yl)amino]benzoate

5-acetyl-2-ethyl-4-[(2-forfinal)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(2-chlorophenyl)amino]-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-3-ileribasi-3(2H)-he

3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridin-4-yl)amino]benzonitrile

5-acetyl-4-[(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-4-[(3,5-dichlorophenyl)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-4-[(2-forfinal)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(2-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ileribasi-3(2H)-he

3-{[5-acetyl-2-(cyclopropylmethyl)-3-oxo-6-pyridin-3-yl-2,3-dihydropyridin-4-yl]amino}benzonitrile

methyl-4-{[5-acetyl-2-(2-hydroxyethyl)-3-oxo-6-pyridin-3-yl-2,3-dihydropyridin-4-yl]amino}benzoate

5-acetyl-4-[(2-forfinal)amino]-2-(2-hydroxyethyl)-6-Piri Dean-3-ileribasi-3(2H)-he

5-acetyl-4-[(2-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-2-Alperin-3(2H)-he

3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-2-yl-2,3-dihydropyridin-4-yl)amino]benzonitrile

5-acetyl-2-ethyl-4-{[4-(g is proximity)phenyl]amino}-6-pyridin-2-ileribasi-3(2H)-he

3-{[5-acetyl-2-(cyclopropylmethyl)-3-oxo-6-pyridin-2-yl-2,3-dihydropyridin-4-yl]amino}benzonitrile

5-acetyl-4-[(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-2-ileribasi-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-2-ileribasi-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-4-[(3,5-dichlorophenyl)amino]-6-pyridin-2-ileribasi-3(2H)-he

3-{[5-acetyl-2-(2-hydroxyethyl)-3-oxo-6-pyridin-2-yl-2,3-dihydropyridin-4-yl]amino}benzonitrile

5-acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-2-ileribasi-3(2H)-he

5-acetyl-4-[(3,5-dichlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-2-ileribasi-3(2H)-he

5-acetyl-2-(2-hydroxyethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-2-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(3-forfinal)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(1-naphthylamine)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(2-were)amino]-6-pyridin-4-ileribasi-3(2H)-he

methyl-4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl)amino]benzoate

5-acetyl-2-ethyl-4-[(2-methoxyphenyl)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(3-methoxyphenyl)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(2-forfinal)and the Ino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(2-chlorophenyl)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl)amino]benzonitrile

5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-4-ileribasi-3(2H)-he

4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl)amino]benzoic acid

5-acetyl-2-(cyclopropylmethyl)-4-[(2-forfinal)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(2-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-4-ileribasi-3(2H)-he

3-{[5-acetyl-2-(cyclopropylmethyl)-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl]amino}benzonitrile

5-acetyl-2-(cyclopropylmethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(2-forfinal)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(2-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ileribasi-3(2H)-he

3-{[5-acetyl-2-(2-hydroxyethyl)-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl]amino}benzonitrile

5-acetyl-2-(2-hydroxyethyl)-4-{[4-(hydroxymethyl)phenyl]amino}-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-Tien-2-ileribasi-3(2 is)-he

5-acetyl-4-[bis(3-forfinal)amino]-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[bis-(4-ethoxycarbonylphenyl)-amino]-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-{bis[4-(hydroxymethyl)phenyl]amino}-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-nitrophenyl)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-forfinal)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[bis(3,5-dichlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[bis(4-ethoxycarbonylphenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-2-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-chlorophenyl)amino]-2-(cyclopropylmethyl)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-4-[(3,5-dichloropyridine-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(pyrazin-2-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(pyrimidine-2-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(quinoline-8-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(5-nitropyridine-2-yl)amino]-6-phenylpyridazin-3(2H)-he

5-Aza the Il-2-ethyl-4-(1H-indol-4-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-4-(1,3-benzothiazol-6-ylamino)-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(tianren-1 ylamino)pyridazin-3(2H)-he

methyl-3-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]thiophene-2-carboxylate

5-acetyl-2-ethyl-4-[(4-methylpyridin-2-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(1H-1,2,4-triazole-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(6-methoxypyridine-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(2H-indazol-5-ylamino)-6-phenylpyridazin-3(2H)-he

methyl-4-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]thiophene-3-carboxylate

5-acetyl-2-ethyl-6-phenyl-4-(pyridine-2-ylamino)pyridazin-3(2H)-he

3-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]thiophene-2-carboxylic acid

5-acetyl-2-ethyl-4-[(3-methylcinnamic-5-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-methylinosine-8-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1H-indol-5-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-5-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(6-methoxyquinoline-8-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(5-bronchioles-8-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-AC is Teal-2-ethyl-4-[(4-methylpyrimidin-2-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-(cyclopropylmethyl)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-forfinal)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-6-(3-forfinal)-2-isopropyl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(3-forfinal)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-6-(1H-benzimidazole-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridine-3(2H)-he

5-acetyl-6-(1,3-benzoxazol-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridine-3(2H)-he

5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-[(3-forfinal)amino]pyridazin-3(2H)-he

5-acetyl-6-benzoxazol-2-yl-4-[bis-(3-chlorophenyl)-amino]-2-ethylpyridine-3(2H)-he

5-acetyl-6-benzoxazol-2-yl-4-[bis-(3-forfinal)-amino]-2-ethylpyridine-3(2H)-he

3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridin-4-yl)amino]benzamide

5-acetyl-2-ethyl-4-(isoquinoline-1-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(2-butylbenzoyl-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-4-(1,2-benzothiazol-3-ylamino)-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(pyridine-4-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-hydroxy-7H-purine-6-yl)amine is]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(hinzelin-4-ylamino)pyridazin-3(2H)-he

5-acetyl-4-[(4-chloro-1H-indazol-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(7-chlorhydrin-4-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(4,6-dichloropyrimidine-2-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(6-hydroxy-2H-pyrazolo[3,4-(1]pyrimidine-4-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-methylinosine-4-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1H-imidazol-2-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(quinoline-4-ylamino)pyridazin-3(2H)-he

5-acetyl-4-(cinnolin-4-ylamino)-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(1H-pyrazolo[3,4-d]pyrimidine-4-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(thieno[2,3-d]pyrimidine-4-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1H-indazol-6-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-(2-methoxypyridine-4-yl)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}-6-(6-methoxypyridine-3-yl)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(3-methoxyphenyl)amino]-6-Tien-3-ileribasi-3(2H)-he

5-acetyl-6-(1-benzofuran-5-yl)-2-ethyl-4-[(3-forfinal)amino]pyridazin-3(2H)-he

2-ethyl-4-[(3-forfinal)amino]-5-glycolyl-6-pyridin-4-ileribasi-3(2H)he

3-{[2-ethyl-3-oxo-5-(3-phenylpropenoyl)-6-pyridin-4-yl-2,3-dihydropyridin-4-yl]amino}benzamide

5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-[(3-methoxyphenyl)amino]pyridazin-3(2H)-he

5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-{[4-(hydroxymethyl)phenyl]amino}pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1,6-naphthiridine-8 ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(5-methoxypyridine-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-4-yl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-4-yl-4-[(3,4,5-tryptophanyl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-3-yl-4-[(3,4,5-tryptophanyl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(quinoline-5-ylamino)-6-Tien-2-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(pyridine-3-ylamino)-6-Tien-2-ileribasi-3(2H)-he

4-[(5-acetyl-2-ethyl-3-oxo-6-Tien-2-yl-2,3-dihydropyridin-4-yl)amino]benzonitrile

5-acetyl-2-ethyl-6-Tien-2-yl-4-[(3,4,5-tripthe who yl)amino]pyridazin-3(2H)-he

5-acetyl-4-(bis(4-cyanophenyl)amino)-2-ethyl-6-Tien-2-ileribasi-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-4-(quinoline-5-ylamino)-6-Tien-2-ileribasi-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-4-(pyridine-3-ylamino)-6-Tien-2-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(quinoline-5-ylamino)-6-Tien-3-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-Tien-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(pyridine-3-ylamino)-6-Tien-3-ileribasi-3(2H)-he

4-[(5-acetyl-2-ethyl-3-oxo-6-Tien-3-yl-2,3-dihydropyridin-4-yl)amino]benzonitrile

5-acetyl-2-ethyl-6-Tien-3-yl-4-[(3,4,5-tryptophanyl)amino]pyridazin-3(2H)-he

2-ethyl-6-phenyl-5-(3-phenylpropenoyl)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

2-ethyl-6-phenyl-5-(3-phenylpropenoyl)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

2-ethyl-4-(isoquinoline-4-ylamino)-6-phenyl-5-(3-phenylpropenoyl)pyridazin-3(2H)-he

2-ethyl-6-phenyl-4-(quinoline-5-ylamino)-5-(3-Tien-3-ispropanol)pyridazin-3(2H)-he

2-ethyl-6-phenyl-4-(pyridine-3-ylamino)-5-(3-Tien-3-ispropanol)pyridazin-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-(1H-imidazo[4,5-b]pyridine-2-yl)pyridazin-3(2H)-he

5-acetyl-6-(1,3-benzothiazol-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridine-3(2H)-he

5-acetyl-6-(1-benzofuran-2-yl)-4-[(3-chlorophenyl)amino]-2-ethylpyridine-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-3-yl-4-(pyridin-3-yl) - Rev. Mino)pyridazin-3(2H)-he

4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-3-yl-2,3-dihydropyridin-4-yl)amino]benzoic acid

5-acetyl-2-ethyl-4-[(1-oxidability-3-yl)amino]-6-phenylpyridazin-3(2H)-he

ethyl-3-(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-ylamino)benzoate

3-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl)amino]benzamide

5-acetyl-2-ethyl-6-phenyl-4-(thieno[2,3-b]pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(6-herperidin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-4-{[2-(dimethylamino)pyridin-3-yl]amino}-2-ethyl-6-penilee dazin-3(2H)-he

5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]pyridine-2-carboxylic acid

5-acetyl-2-ethyl-4-[(2-methoxypyridine-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1H-indazol-4-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(5-chloropyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]nicotinamide

5-acetyl-2-ethyl-4-(1,7-naphthiridine-8 ylamino)-6-phenylpyridazin-3(2H)-he

2-ethyl-5-glycolyl-4-[(2-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

methyl-5-[(5-acetyl-2-ethyl-3-ox is-6-phenyl-2,3-dihydropyridin-4-yl)amino]nicotinate

5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]nicotinic acid

5-acetyl-2-ethyl-4-(1,5-naphthiridine-3-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(8-hydroxy-1,7-naphthiridine-5-yl)amino]-6-penilee dazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(Tien-2-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-[(2-vinylpyridin-3-yl)amino]pyridazin-3(2H)-he

ethyl-{5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]pyridine-2-yl}acetate

5-acetyl-2-ethyl-4-[(6-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(6-hydroxypyridine-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-herperidin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(6-chloro-4-methylpyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(3-hydroxypyridine-2-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(4-methoxypyridine-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-8-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(quinoline-7-ylamino)pyridazin-3(2H)-he

5-acetyl-4-[(5-chloropyridin-3-yl)amino]-2-ethyl-6-(3-forfinal)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-[(2-methoxypyridine-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-[(2-methylpyridin-3-yl)amino]the feast is dazin-3(2H)-he

5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-ethyl-6-(4-forfinal)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-[(2-herperidin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-(cyclopropylmethyl)-6-(4-forfinal)pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-[(2-methoxypyridine-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-[(2-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-[(2-herperidin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-[(pyridine-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-[(2-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-4-[(2-chloropyridin-3-yl)amino]-2-ethylpyridine-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

methyl-5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]quinoline-8-carboxylate

5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-(4-methoxyphenyl)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-methoxyphenyl)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-methoxyphenyl)-4-(1-oksihinolina-5-ylamino)-2H-pyridazin-3-one

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-(3-methoxyphenyl)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-methoxyphenyl)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-methoxyphenyl)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-methoxyphenyl)-4-[(1-acidogenesis-5-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-(4-were)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-were)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-were)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-were)-4-[(1-acidogenesis-5-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-were)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-(3-were)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-were)-4-(pyridin-3-yl)amino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-were)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-were)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

methyl-4-[4-acetyl-1-ethyl-5-(isoquinoline-4-ylamino)-6-ox is -1,6-dihydropyridin-3-yl]benzoate

methyl-4-[4-acetyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-3-yl]benzoate

4-[4-acetyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-3-yl]benzoic acid

methyl-4-{4-acetyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}benzoate

4-{4-acetyl-1-ethyl-5-[(4-methylpyridin-3-yl)amino]-6-oxo-1,6-dihydropyridin-3-yl}benzoic acid

methyl-3-[4-acetyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-3-yl]benzoate

3-[4-acetyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-3-yl]benzoic acid

5-acetyl-4-[(3-chloro-4-forfinal)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-chloro-4-forfinal)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(3-chloro-4-forfinal)amino]-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[bis(3-chloro-4-forfinal)amino]-2-ethyl-6-pyridin-3-ileribasi-3(2H)-he

methyl-[4-acetyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)pyridazin-1(6N)-yl]acetate

[4-acetyl-6-oxo-3-phenyl-5-(quinoline-5-ylamino)pyridazin-1(6N)-yl]acetic acid

5-acetyl-2-ethyl-4-[(3-methylpyridin-2-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(1H-pyrazole-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(N-purine-6-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(3-methylisoxazol-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(8-hydroxyquinolin-5-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1H-indazol-7-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-4-[(6-bronchioles-8-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(5-methylisoxazol-3-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoxazol-3-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-phenyl-4-(quinoline-5-yl)amino)pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-phenyl-4-(quinoline-8-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(1-methyl-1H-pyrazole-3-yl)amino]-6-phenylpyridazin-(2H)-he

5-acetyl-2-ethyl-4-[(1-acidogenesis-5-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-oxydiethanol-5-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(quinoline-8-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-4-yl-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-3-yl-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(8-ftorhinolon-5-yl)amino]-6-phenylpyridazin-3(2H)he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-(quinoline-8-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-(quinoline-5-ylamino)pyridazin-3(2H)he

5-acetyl-2-stor is l-6-(4-forfinal)-4-(quinoline-8-ylamino)pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(4-forfinal)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-[(1-acidogenesis-5-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(2-methylinosine-5-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-6-(3-chlorophenyl)-2-ethyl-4-(isoquinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-[(1-acidogenesis-5-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-forfinal)-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-forfinal)-4-[(1-acidogenesis-5-yl)amino]pyridazin-3(2H)-he

5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-dihydropyridin-4-yl)amino]quinoline-8-carboxylic acid

and their pharmaceutically acceptable salts.

16. The connection 15, which is one of the following:

5-acetyl-2-ethyl-4-[(3-forfinal)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(1-naphthylamine)-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(1-naphthylamine)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(2-were)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(3-methoxyphenyl)amino]-6-pyridin-4-ileribasi-3(2H)-he

4-[(5-acetyl-2-ethyl-3-oxo-6-pyridin-4-yl-2,3-dihydropyridin-4-yl)amino]benzoic acid

5-is cetyl-4-[(3-chlorophenyl)amino]-2-(2-hydroxyethyl)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-4-[(3-chlorophenyl)amino]-2-ethyl-6-Tien-2-ileribasi-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(quinoline-8-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(1H-indol-4-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(quinoline-5-ylamino)pyridazin-3(2H)-he

5-acetyl-6-(3-forfinal)-2-isopropyl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-(cyclopropylmethyl)-6-(3-forfinal)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-5-ylamino)-6-phenylpyridazin-3(2H)-he

5-acetyl-6-(1,3-benzoxazol-2-yl)-2-ethyl-4-[(3-forfinal)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(1-acidogenesis-5-yl)amino]-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-phenylpyridazin-3(2H)-he

2-ethyl-6-phenyl-5-(3-phenylpropenoyl)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-(3-were)pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-(isoquinoline-4-ylamino)-6-(4-were)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-forfinal)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-[(5-acetyl-2-ethyl-3-oxo-6-phenyl-2,3-what hydropyridine-4-yl)amino]quinoline-8-carboxylic acid

5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

methyl-3-[4-acetyl-1-ethyl-6-oxo-5-(pyridine-3-ylamino)-1,6-dihydropyridin-3-yl]benzoate

5-acetyl-2-ethyl-6-(3-were)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-(pyridine-3-ylamino)-6-Tien-3-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(2-methylpyridin-3-yl)amino]-6-phenylpyridazin-3(2H)-he

methyl ester of 3-(4-acetyl-5-amino-1-ethyl-6-oxo-1,6-dihydropyridin-3-yl)-benzoic acid

5-acetyl-2-ethyl-6-(3-were)-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(3-forfinal)-4-(pyridine-3-ylamino)-pyridazin-3(2H)-he

5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-4-ileribasi-3(2H)-he

5-acetyl-2-ethyl-4-[(4-methylpyridin-3-yl)amino]-6-pyridin-3-ileribasi-3(2H)-he

5-acetyl-4-[(2-chloropyridin-3-yl)amino]-2-ethyl-6-phenylpyridazin-3(2H)-he

5-acetyl-2-ethyl-6-pyridin-3-yl-4-(pyridine-3-ylamino)pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-(4-were)-4-[(4-methylpyridin-3-yl)amino]pyridazin-3(2H)-he

5-acetyl-2-ethyl-6-phenyl-4-(thieno[2,3-b]pyridine-3-ylamino)pyridazin-3(2H)-he.

17. The method of obtaining the compounds of formula (XXIV)

in which R1represents C1-6alkyl group, R2denotes a hydrogen atom, R3putting the AET phenyl group, substituted with halogen, R4stands With1-6alkyl group, each G1, G2, G3denote the nitrogen atom, and G4denotes the nitrogen atom or carbon, Y denotes the atom, S atom or-NH-group, where the method involves the complex interaction of ether carboxylic acids of the formula (VII)

in which R1, R2, R3and R4are as defined above, and R7represents C1-6alkyl group, with ortho-substituted aniline of formula (VIII)

where each G1, G2, G3and G4are as defined above and Y denotes an amino, mercapto or hydroxy - group, in the presence of a dehydrating reagent.

18. The compound of formula (XXV)

in which M2denotes a hydrogen atom and M3denotes a hydrogen atom or phenyl group, in which R1, R4and R7are as defined in 17.

19. Connection p, which represents ethyl-4-acetyl-5-amino-1-ethyl-6-oxo-1,6-dihydropyridin-3-carboxylate.

20. The compound according to any one of claims 1 to 16 for use in the treatment of the human or animal.

21. Pharmaceutical composition having inhibitory activity against F. studiesthere 4, comprising the compound according to any one of claims 1 to 16, mixed with a pharmaceutically acceptable diluent or carrier.

22. The use of compounds according to any one of claims 1 to 16 in the manufacture of a medicinal product intended for treating or preventing a pathological condition or disease, the occurrence of which is facilitated by inhibition of phosphodiesterase 4.

23. The application of article 22, in which the drug is intended for use in the treatment or prevention of disorders, which is asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis or irritable bowel syndrome.

24. The method of treatment of a subject suffering from a pathological condition or disease, the occurrence of which is facilitated by inhibition of phosphodiesterase 4, which method includes the introduction of a specified subject an effective amount of a compound according to any one of claims 1 to 16.

25. The method according to paragraph 24, in which the pathological condition or disease is asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, atopic dermatitis, psoriasis or irritable bowel syndrome.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention concerns method of obtaining heterocycles of formula I , where X, A, R10-R17 are as defined in point 1 of the claim, while a) isothiocyanate of formula II is transformed into thiourea of formula IV by interaction with primary amine of formula III, and b) thiourea of formula IV is transformed into compound of formula I by interaction with sulfochloride R6SO2Cl in the presence of a base, where A, X, n, m and R10 to R17 in compounds of formulae II, III and IV are as defined in formula I, and R6 is (C1-C4)-alkyl, trifluoromethyl or phenyl non-sustituted or substituted by methyl, trifluoromethyl, F, CI, Br or polymer carreir. The transportation is shown by combination formulae

EFFECT: new multipurpose synthesis technique for heterocyclic compounds of the general formula I.

8 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new photochromic monomers

Alk=CH3-C10H21 X=Cl, Br, I, F, NH2, CH2OH, CH2Cl, CH2Br, CHO, CO2H, method of obtaining them, photochromic polymers- polyazomethines, which are reversibly photocontrolled due to introduction into their structure, of dihetarylenthane class photochromic fragments.

EFFECT: obtaining new photochromic photocontrolled polymers for designing new information technologies.

8 cl, 25 dwg, 15 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to new photochromic monomers and new polymers based on such monomers, intended for use in making two-photon photochromic recording media for three dimensional optical memory and photoswitches of optical signals. Description is given of monomers

Q=; ; ;

Alk=CH3-C10H21 X=Cl, Br, I, F, NH2, CH2OH, CH2Cl, CH2Br, CHO, CO2H and X=CH2, O, S, NAlk; Y=O, S, NAlk; n=0-6; Q=; ; ; ; ;

Alk=CH3-C10H21, methods of obtaining them, photochromic polymers based on them, method of obtaining photochromic monomers and their application. The proposed materials exhibit thermal irreversibility of photochromic transformations and properties, making it possible to use photochromic polymers in two-photon random access optical memory.

EFFECT: obtaining materials with thermal irreversibility of photochromic transformations and properties, making it possible to use photochromic polymers in two-photon random access optical memory.

15 cl, 46 dwg, 31 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1: , where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.

EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.

16 cl, 5 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: claimed invention relates to method of obtaining derivatives of 8-thieno[2,3-b]indole of general formula I and can be used for obtaining biologically active substances. Method is characterised by the fact that derivatives of 2-alkyl-5-(2-isothiocyanoaryl)furanes are mixed in 1,2-dichloroethane in presence of aluminium chloride with molar ratio of initial substance and aluminium chloride 1:1÷1:2 at temperature from room temperature to temperature of 1,2-dichloroethane boiling for from 30 min to 48 hours. I a-e, Ia R1 = H, R2 = CH3, b R1 = H, R2 = CH2CH3, c R1 = CI, R2 = CH3, d R1 = CH3, R2 = CH3, e R1 = OCH3, R2 = CH3.

EFFECT: extension of series of potentially biologically active derivatives of the said agent.

1 cl, 6 ex, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to 2,2'-di(3,4-alkylenedioxythiophene)s of general formula (I) , where A, R and x have given in description values, which are intended for obtaining electroconducting or semiconducting compounds and valuable semi-products for π-conjugated polymers. Also described is method of their obtaining and method of obtaining poly(3,4-alkylenedioxythophene)s based on them. Claimed method allows to obtain novel 2,2'-di(3,4-alkylenedioxythiophene)s by simplified techniques and extend possibilities of their application.

EFFECT: obtaining agents by simplified techniques and extension of possibilities of their application.

12 cl, 4 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: claimed invention relates to novel azaheterocycles of general formula 1.1-13 and 2, as well as their pharmaceutically acceptable salts, which possess anti-carcinogenic activity, pharmaceutical composition with their application and combinatorial and focused libraries including novel azaheterocycles. In general formulae 1.1-1.3 and 2.

.

For compounds 1.1-1.3 each of R1a R2a independently on each other represent possibly substituted C1-C6alkyl; each of R1d, R2d, R3d, R4d, R5d, R6d and R7d independently on each other represent substitutes of cyclic system, preferably hydrogen atom, or for compounds 1.1 and 1.3 independently R1d and R2d, R3d and R4d, R5d and R6d together with atoms with which they are bound can form through R1d and R2d, R3d and R4d, R5d and R6d respectively, possibly substituted aromatic cycle, such as benzole, 5-6-member heterocycle which includes, at least, one of heteroatoms, selected from S; or for compounds 1.2 independently R1d and R2d, R3d and R4d, R4d and R5d, R6d and R7d together with atoms with which they are bound can form through R1d and R2d, R3d and R4d, R4d and R5d, R6d and R7d respectively, possibly substituted aromatic cycle, such as benzole, 5-6-member heterocycle which includes, at least, one of heteroatoms, selected from S; for compound 2 R1a represents amino group substitute, excluding hydrogen atom, such as possibly substituted C1-C6alkyl, possibly substituted phenyl; R2a represents possibly substituted C1-C6alkyl; R3a represents amino group substitute, such as hydrogen atom, possibly substituted C1-C6alkyl; Rnd represents one or two substitutes of cyclic system, preferably hydrogen atom, solid line with accompanying it dotted line represent single or double bond.

EFFECT: obtaining novel azaheterocycles and their pharmaceutically acceptable salts, which possess anti-carcinogenic activity.

9 cl, 4 dwg, 3 tbl, 7 ex

FIELD: chemistry, pharmaceutics.

SUBSTANCE: invention relates to method of obtaining 4-amino-3-quinolinecarbonitryl, which includes: a) combining aminocompound with cyanoacetic acid and acid catalyst obtaining cyanoacetomide; b) condensing cyanoacetomide from stage a with aniline, alcohol solvent and trialkylorthoformiate obtaining 3-amino-2-cyanoakrylamide; and c) combining 3-amino-2-cyanoakrylamide with phosphorus oxychloride in acetonitryl, butyronitrile, toluol or xylol, optionally in presence of catalyst, obtaining 4-amino-3-quinolinecarbonitryl. Also described is method (version) of obtaining 4-amino-3-quinolinecarbonitryl, method of obtaining 7-aminothieno[3,2-b]pyridine-6-carbonitrile and method of obtaining cyanoacetamide.

EFFECT: creation of efficient method of obtaining 4-amino-3-quinolinecarbonitryl.

24 cl, 50 ex

FIELD: medicine; pharmacology.

SUBSTANCE: new annelated asaheterocycles include pyrimidine fragment of general formula I in the form of free bases or pharmaceutically acceptable salts. Compounds of this invention possess properties of PI3 kinase inhibitors. In general formula I X represents oxygen atom or sulphur atom; Z represents oxygen atom, R1 represents hydrogen atom or optionally substituted C1-C6alkyl, or Z represents nitrogen atom together with bound carbon atom forming through Z and R1 optionally substituted annelated imidazoline cycle; R2 represents optionally substituted C1-C6alkyl, optionally substituted C3-C8cycloalkyl, optionally substituted phenyl, possibly annelated with 5-6-term heterocyclyl containing heteroatoms chosen from oxygen and nitrogen, optionally substituted 5-6-term heterocyclyl containing heteroatoms chosen from nitrogen, oxygen and/or sulphur, possibly annelated with phenyl ring. Invention also concerns method of production of compounds, pharmaceutical compositions and medical products.

EFFECT: effective application for preparation of medical products for oncologic therapy.

14 cl, 3 dwg, 1 tbl, 4 ex

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

FIELD: chemistry.

SUBSTANCE: present invention relates to new annelated azaheterocyclic amides, including a pyrimidine fragment, with the general formula 1, method of obtaining them and their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of P13K kinase, in compounds with the general formula 1: , where: X represents an oxygen atom, sulphur atom or not necessarily substituted at the nitrogen NH group, where the substitute is selected from lower alkyls and possibly a substituted aryl; Y represents an atom of nitrogen or substituted at the carbon atom CH group, where the substitute is selected from lower alkyls; Z represents an oxygen atom; R1 represents a hydrogen atom or not necessarily substituted C1-C6alkyl, or Z represents a nitrogen atom, which is together with a carbon atom, with which it is joined, form through Z and R1 annelated imidazole cycle; R2 and R3 independently from each other represent hydrogen, not necessarily substituted with C1-C6alkyl, C3-C6cycloalkyl, not necessarily substituted with phenyl, not necessarily substituted with 6-member aza-heteroaryl, under the condition, when Y represents a nitrogen atom, or R2 and R3 independently from each other represent not necessarily substituted C1-C6alkyl, not necessarily substituted with phenyl, not necessarily substituted with 5-7-member heterocycle with 1-2 heteroatoms, selected from nitrogen and oxygen, and possibly annelated with a phenyl ring, under the condition, when Y does not necessarily represent a substituted carbon atom at the CH group, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents a substituted aminoC1-C6alkyl and not necessarily substituted 5-6-member aza-heterocycloalkyl, under the condition, when Y represents a group which is substituted at the CH atom, and X represents an oxygen atom, sulphur atom, or R2 represents hydrogen, and R3 represents phenyl which is not necessarily substituted, pyridyl which is not necessarily substituted, pyrimidinyl which is not necessarily substituted, under the conditions, when R1 represents a substituted aminoC1-C6alkyl, substituted C2-C3hydroxyalkyl and aza-heterocycloalkyl not necessarily substituted, Y represents a group with CH substituted, and X represents an oxygen atom, sulphur, and the substitute of the above indicated substituted alkyl, phenyl, heterocycle, pyridyl, pyrimidyl are selected from groups of hydroxyl-, cyano-groups, hydrogen, lower alkyls, possibly mono- or di-substituted lower alkyl sulfamoyl, carbamoyl, C1-C6alkoxycarbonyl, amino, mono- or di-lower alkyl-amine, N-(lower alkyl), N-(phenylC1-C6alkyl)amine, phenyl, possibly substituted with a halogen atom, C1-C6alkyl, haloid-C1-C6alkyl; phenylC1-C6alkyl, saturated or non-saturated 5-6-member heterocycle containing 1-2-heteroatoms, selected from nitrogen, oxygen and sulphur, and possible condensation with a benzene ring R4 represents hydrogen or a lower alkyl.

EFFECT: obtaining new annelated aza-heterocyclic amides, including a pyrimidine fragment, with the general formula with the possibility of their application in the form of free bases or their pharmaceutically accepted salts as inhibitors of PI3K kinase.

16 cl, 5 tbl, 5 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to methane sulphonate of 8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazol[1,5-a]pyrimidine, its crystal and method of obtaining it. Methane sulphonate of 8-(3-pentylamino)-2-methyl-3-(2-chloro-4-methoxyphenyl)-6,7-dihydro-5H-cyclopenta[d]pyrazol[1,5-a]pyrimidine has excellent thermal stability. The invention also relates to pharmaceutical compositions based on the above mentioned salt and its crystal. The compositions are CRF antagonists and can be used for treating neuropsychiatric disorders or alimentary system diseases. The invention also pertains to an efficient high output new method of making the intermediate compound 1-cyano-1-(2-chloro-4-methoxyphenyl)propan-2-one from 1-bromo-2-chloro-4-methoxybenzol.

EFFECT: obtaining intermediate compound with efficient high output.

16 cl, 6 dwg, 10 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a new compound - acid mesylate of 4-(4-trans-hydroxycyclohexyl) amino-2-phenyl-7H-pyrrolo [2,3d]pyrimidine and its polymorphous α and β forms. The compound has agonistic activity towards adenosine-1 receptor and can be used for making medicinal preparations for treating hypertensive diseases, congestive heart failure and renal failure.

EFFECT: obtaining a compound with better bioavailability due to high solubility and which is more stable in ambient conditions.

17 cl, 6 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: described is 4-(4'-hydroxybutyl)-6-phenyl-1,2,4-triazolo[5,1-c] [1,2,4]triazin-7-on of formula (1) possessing anti-viral activity, , which can be applied in medicine and agriculture.

EFFECT: obtaining compound which possesses antiviral activity.

1 cl, 3 ex, 1 tbl

FIELD: chemistry, pharmaceutics.

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

,

,

,

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

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

32 cl, 5 dwg, 118 ex

FIELD: chemistry.

SUBSTANCE: this invention refers to new production method of composition of formula I where R1 represents: H; cyano; optionally unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group; or -C(O)-R5, where R5 represents H; optionally unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group; either OR6 or NR6R7 where each R6 and R7 independently represents H optionally unsubstituted or substituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl group; R2 represents H; R3 represents H or alkyl; R4 represents H, halogen or alkyl including: a) Sonogashira coupling of formula II , where X represents halogen or CF3SO2-O- with compound of formula III to produce compound of formula IV ; b) reduction of connection of formula IV to produce compound of formula V ; c) transformation of compound of formula V into compound of formula VI ; d) N,N-dimethyl-2-nitroethylenamine treatment of compound of formula VI to produce compound of formula VII ; e) reduction of connection of formula VII to produce compound of formula VIII ; f) of compound of formula VIII by Raney-nickel reduction and subsequent base ring formation into compound of formula I. Besides described is production method of 8-fluorine-2-{4-[(methylamino)methyl]phenyl}-1,3,4,5-tetrahydro-6H-azepino[5,4,3-cd]indole-6-one through key Sonogashira coupling reaction and CuI-promotor indole production.

EFFECT: new production method of compounds of formulas I effective as poly(ADP-ribose)polymerase inhibitors is developed.

8 cl, 13 ex

FIELD: chemistry.

SUBSTANCE: sodium salt of 2-methylthio-6-nitro-1,2,4-triazolo[5,1-c]-1,2,4-triazin-7-one, dehydrate of formula (1) is obtained by interaction of salt of 3-methylthio-1,2,4-triazol-5-yl-diazonium with diethylnitromalonate in presence of base at 0-25°C in water-alcohol medium.

EFFECT: compound possesses antivirus activity and can find application in medicine.

1 cl, 1 tbl, 1 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to new condensed dicyclic nitrogen-containing heterocycles with the general formula (I), their pharmaceutically accepted salts and stereoisomers, possessing DGAT inhibiting action. In the compound of formula (I): , X is selected from a group, which consists of C(R1) and N; Y is selected from a group, which consists of C(R1), C(R2)(R2), N and N(R2); Z is selected from a group, which consists of O; W1 is selected from cyclo(C3-C6)alkyl, aryl and 5- or 6-member heteroaryl, containing 1-2 heteroatoms, selected from a group, which comprises of nitrogen and sulphur, W2 selected from cyclo(C3-C8)alkyl, (C5-C6)heterocycloalkyl, containing 1 or 2 heteroatoms, selected from groups, consisting of nitrogen or oxygen, benzol and 5-or 6-member heteroaryl, containing 1-2 nitrogen atoms as heteroatoms, L1 is the link; L2 is selected from a group consisting of links, 0, (C1-C4)alkylene and (C1-C4)oxyalkylene; m denotes 0 or 1; its not a must that when m denotes 1 and L2 denotes a link, the substitute for W2 can be integrated with the substitute for W1 forming a 5-or 6-member ring, condensed with c W1 forming a spiro-system or condensed with W2, where specified ring could be saturated or unsaturated and has 0 or 1 atom O, as a member of the ring R1 is H; R2 is H; R3 and R4 are independently selected from groups consisting of H and (C1-C8) alkyl; optionally, R3 and R4 can together form 3-, 4-, 5- or 6-member spirorings, R5 and R6 are independently H; optionally, when Y includes the group R1 or R2, R5 or R6 can be joined with R1 and R2 forming a 5- or 6-member condensate ring, containing a nitrogen atom, to which R5 or R6 are joined, and optionally containing an oxo-group; R7 is selected from a group, composed of H, (C1-C8) alkyl, halogen(C1-C4)alkyl, 0Ra and NRaRb ; Ra selected from groups composed of H and (C1-C8)alkyl; and Rb selected from groups consisting of H and (C1-C8)alkyl; a dotted line indicates a possible bond. The invention also relates to pharmaceutical compositions and applications of the compounds.

EFFECT: obtaining compounds which can be used for getting medicinal agents to treat or prevent diseases or a mediated action state of DGAT, such as obesity, diabetes, syndrome X, resistance of insulin, hyperglycemia, hyperinsulinemia, hypercholesterolemia, hyperlipidemia, hypertriglyceridemia, disease of non-alcoholic fatty infiltration of the liver, atherosclerosis, arteriosclerosis, coronary artery disease and myocardial infarction.

33 cl, 17 dwg, 11 tbl, 391 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: present invention relates to new compounds with general formula (1), which includes compounds (VI), which relate to conformational stable compounds that imitate the secondary structures of parts of molecules of biologically active peptides and proteins with reverse configurations. The compounds can be used as antitumoral compounds for the treatment and prophylaxis of cancer such as, colorectal cancer, for treating rheumatoid arthritis and ulcerative colitis. The compound facilitates the increase of apoptosis and increases the proliferation of neurites, and inhibits survirin expression in the cell. In compounds, corresponding to the general formula (I) and (VI) , in formula (I) W denotes -Y(C=O)-, -(C=O)NH-, -(SO2)- or is absent, Y denotes an oxygen atom, Z denotes a nitrogen atom or CH, X denotes a nitrogen atom or CH, n=0 or 1, on the condition that when Z denotes CH, X denotes a nitrogen atom and n=1; and when Z denotes a nitrogen atom, then n=0; in formula (VI) X1 denotes a hydroxyl, and at least one of X2 is X3 is a hydroxyl, or X1 denotes hydrogen, and X2 and X3 can be similar of different and independently selected from hydrogen, hydroxyl and halogen. Other radicals have the value specified in the formula of the invention.

EFFECT: obtaining compounds which can be used as antitumoral compounds for the treatment and prophylaxis of cancer such as, colorectal cancer, for treating rheumatoid arthritis and ulcerative colitis.

26 cl, 33 dwg, 9 tbl, 14 ex

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

FIELD: chemistry.

SUBSTANCE: description is given of a lactam-containing compound-derivative of tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carboxamide with formula I , its pharmaceutical salt and pharmaceutical compositions, their content, and their use as Xa factor inhibitors. The given compound can be used for treating thromboembolic diseases.

EFFECT: obtaining a lactam-containing compound, which can be used for treating thromobembolic diseases.

42 cl, 9 tbl, 140 ex

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