Condensed pirimidine derivative and pharmaceutics with crf related activity

FIELD: chemistry.

SUBSTANCE: invention relates to the novel compounds with formula I or their pharmaceutically acceptable salts and based on them pharmaceutics with the CRF (corticotrophin releasing factor) related activity. In the common formula I , X1 means (CH2)n, where n equal to 0-2, R1 means (1)C1-C10alkyl or C1-C10alkenyl, not necesserily substituted with substitute, selected from the group, including hydroxy, cyano, (C1-C3alkyl)arylamino and phenyl, and said phenyl not necesserily substituted with one-three substitutes, independently selected from the group including C1-C6alkyl, C1-C6alkoxi, halogen, (2) C3-C7cycloalkyl, not necesserily substituted with hydroxy,(3) C3-C7cycloalkyl(C1-C3)alkyl or C3-C7cycloalkenyl(C1-C3)alkyl,(4) C4-C12tricyclic alkyl,(5)C3-C7heterocycloalkyl or C3-C7heterocycloalkyl(C1-C3)alkyl, where each of the heterocyclic rings contains in the ring 1-2 heteroatoms, selected from nitrogen, oxygen or sulfur, and not necesserily can be substituted with the group C1-C3alkyl, phenyl or phenyl(C1-C6)alkyl, or the CH2 group in the heterocycloalkyl residue is substituted with C=O,(6) benzo-condensed (C5-C7)cycloalkyl,(7) phenyl, and said phenyl is not necesserily substituted with one-three substitutes, independently selected from the group including C1-C6alkyl, C1-C6alkoxi, methylendioxy, halogen, (8) naftyl, (9) heteroaryl(C1-C6)alkyl, and said heteroaryl(C1-C6)alkyl has 5-6 atoms in the ring and contains 1-2 heteroatoms, selected from nitrogen, oxygen or sulfur, can be condensed with the benzene ring and not necesserily substituted with one-three substitutes, selected from the group, including C1-C6alkyl, (10) 1,2-diphenylethyl,(12) C1-C3alkoxi(C1-C6)alkyl or (13) aryloxy(C1-C6)alkyl, R2 means C1-C6alkyl, R3 means (1) hydrogen,(2) C1-C6alkyl, not necesserily substituted with the group C1-C3acyloxy,(3) C3-C6alkenyl,(8) benzene, and R4 means phenyl, not necesserily substituted with one-three substitutes, independently selected from the group including C1-C6alkyl, halogen.

EFFECT: compounds can be used in treatment of phobias, stress dependent disorders, mental disorders, gastro-intestine disfunctions, neurodegenerative and other psychoneurologic disease.

19 cl, 2 dwg, 2 tbl, 8 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula formula I

where X1means (CH2)nwhere n is 0-2,

R1means

(1)C1-C10alkyl or C2-C10alkenyl, optionally substituted Deputy selected from the group comprising hydroxy, cyano, (C1-C3alkyl)arylamino and phenyl, with the specified phenyl optionally substituted with one to three substituents, independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen,

(2)3-C7cycloalkyl, optionally substituted hydroxy,

(3) (C3-C7cycloalkyl(C1-C3)alkyl or C3-C7cycloalkenyl(C1-C3)alkyl,

(4)4-C12tricyclic alkyl,

(5)3-C7heteroseksualci or3-C7heteroseksualci(C1-C3)alkyl, where each of the heterocyclic group contains 1-2 ring heteroatoms selected from nitrogen, oxygen or sulfur, and optionally may be substituted by a group of C1-C3alkyl, phenyl or phenyl(C1-C6)alkyl, or the group CH2in heterocyclicamines residue substituted at C=O,

(6) benzoannelirovannykh(C5-C7)cycloalkyl,

(7) phenyl, and specified phenyl optionally substituted with one to three replace the s, independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, methylenedioxy, halogen,

(8) naphthyl,

(9) heteroaryl(C1-C6)alkyl, with the specified heteroaryl(C1-C6)alkyl is of 5-6 atoms in the ring and contains 1-2 heteroatoms selected from nitrogen, oxygen or sulfur, can be condensed with a benzene ring and optionally substituted with one to three substituents selected from the group comprising C1-C6alkyl,

(10) 1,2-diphenylether,

(12)1-C3alkoxy(C1-C6)alkyl, or

(13) aryloxy(C1-C6)alkyl,

R2means C1-C6alkyl,

R3means

(1) hydrogen,

(2) C1-C6alkyl, optionally substituted C1-C3acyloxy,

(3) (C3-C6alkenyl,

(8) benzyl, and

R4means phenyl,optionally substituted with one to three substituents, independently selected from the group comprising C1-C6alkyl, halogen, or its pharmaceutically acceptable salt.

2. The connection of claim 1, wherein X1means (CH2)nwhere n is 0-2, R1means

(1) C1-C10alkyl, optionally substituted Deputy selected from the group comprising (C1-sub> 3alkyl)arylamino and phenyl, with the specified phenyl optionally substituted with one to three substituents, independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen,

(2)3-C7cycloalkyl,

(3) (C3-C7cycloalkyl(C1-C3)alkyl,

(4) benzo(C5-C7)cycloalkyl,

(5) phenyl, and specified phenyl optionally substituted with one to three substituents, independently selected from the group comprising C1-C6alkyl, C1-C6alkoxy, halogen,

(6) heteroaryl(C1-C6)alkyl, with the specified heteroaryl(C1-C6)alkyl optionally substituted with one to three substituents selected from the group comprising C1-C6alkyl,

(7) 1,2-diphenylether,

(8)1-C3alkoxy(C1-C6)alkyl, or

(9) aryloxy(C1-C6)alkyl,

R2means C1-C6alkyl,

R3means

(1) hydrogen,

(2) C1-C6alkyl, optionally substituted C1-C3acyloxy,

(3) (C3-C6alkenyl,

(8) benzyl, and

R4means phenyl, optionally substituted with one to three substituents, independently selected from the group comprising C1-C6lcil, halogen, or their pharmaceutically acceptable salts.

3. The compound according to claim 2, where n is 0,

R1means

(1) a branched or unbranched C1-C10alkyl, or

(2) optionally substituted heteroaryl(C1-C6)alkyl, where the specified heteroaryl optionally substituted Deputy selected from the group comprising C1-C3alkyl,

(3) optionally substituted phenyl, and specified phenyl optionally substituted by a Deputy selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen,

(4) C1-C3alkyl, substituted phenyl group, and specified phenyl optionally substituted by a Deputy selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen,

R3means hydrogen, C1-C6alkyl, or benzyl, and

R4means optionally substituted phenyl.

4. The compound according to claim 3, where R1means

(1) a branched or unbranched C1-C10alkyl,

(2) C1-C10alkyl, substituted phenyl group, and specified phenyl optionally substituted, or

(3) heteroaryl(C1-C6)alkyl, where the specified heteroaryl means 2-thienyl, 2-furanyl or 3-indolinyl, each heteroaryl optional is substituted on.

5. The compound according to claim 4, where R4means 2,4-disubstituted or 2,4,6-triple-substituted phenyl.

6. The compound according to claim 5, where X1means (CH2)n, n is 0,

R2means of CH3, R3means of CH2CH3, a R4means 2,4-disubstituted or 2,4,6-triple-substituted phenyl.

7. The connection according to claim 6, selected from the group comprising ethyl[7-(1-ethylpropyl)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

(7-cyclopropyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)ethyl(2,4,6-trimetilfenil)amine,

(7-cyclohexylmethyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(1,2,3,4-tetrahydronaphthalen-1-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl{4-methyl-7-[2-(1-methylpyrrolidine-2-yl)ethyl]-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl}(2,4,6-trimetilfenil)amine,

ethyl(7-indan-1-yl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

ethyl(4-methyl-7-naphthalene-1-ylmethyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(tetrahydrofuran-2-ylmethyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl(4-methyl-7-thiophene-2-ylmethyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

(7-benzo[1,3]dioxol-ylmethyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(3-morpholine-4-ylpropyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(2-pyridin-2-retil)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl(4-methyl-7-pyridin-3-ylmethyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

[7-(1-benzylpiperidine-4-yl)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(2-piperidine-1-retil)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

[7-(1,2-diphenylether)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl(7-isopropyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

ethyl[7-(2-methoxy-1-methylethyl)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(1-methyl-3-phenylpropyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

(7-benzyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl[7-(3-terbisil)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

[7-(3,4-dimethoxybenzyl)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl(4-methyl-7-phenethyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimethylphenyl is)amine,

(7-allyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl(4-methyl-7-propyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

ethyl(4-methyl-7-pentyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)(2,4,6-trimetilfenil)amine,

ethyl[7-(3-imidazol-1-ylpropyl)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

[7-(2-cyclohex-1-teletel)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

3-{2-[ethyl(2,4,6-trimetilfenil)amino]-4-methyl-5,6-dihydropyrrolo[2,3-d]pyrimidine-7-yl}propionitrile,

(7-cyclopropylmethyl-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(1-phenylpropyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl{7-[1-(4-forfinal)ethyl]-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl}(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(2-phenoxyethyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

[7-(1-benzylpyrrolidine-3-yl)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl{7-[2-(3-forfinal)ethyl]-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl}(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(3-propoxyphenyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

[7-(2-[1,3]dioxolane-2-retil)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(5-methylpyrazine-2-ylmethyl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

{7-[2-(1-benzylpiperidine-4-yl)ethyl]-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl}ethyl(2,4,6-trimetilfenil)amine and

[7-(2,4-dimetilfenil)-4-methyl-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl]ethyl(2,4,6-trimetilfenil)amine,

and their acid additive salts with triperoxonane acid.

8. The compound according to claim 5, where X1means (CH2)nn is 0, R1means SN(n-propyl)2, R2means of CH3, R3means of CH2CH3and R4means 2,4-disubstituted or 2,4,6-triple-substituted phenyl.

9. The compound of claim 8 selected from the group including

methyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

ethyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

isopropyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

butyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

cyclopentyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)and is in

4-[[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amino]butyl ester acetic acid, benzyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

cyclopropylmethyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine and allyl[4-methyl-7-(1-propinball)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-2-yl](2,4,6-trimetilfenil)amine,

and as well as their acid additive salts with triperoxonane acid.

10. The compound according to claim 2, where n is 1,

R1means

(1) a branched or unbranched1-C10alkyl, or

(2) optionally substituted heteroaryl(C1-C6)alkyl, where the specified heteroaryl optionally substituted Deputy selected from the group comprising C1-C3alkyl,

(3) optionally substituted phenyl, and specified phenyl optionally substituted by a Deputy selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen,

(4) C1-C3alkyl, substituted phenyl group, and specified phenyl optionally substituted by a Deputy selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen,

R3means hydrogen, C1-C6lkyl or benzyl,

R4means optionally substituted phenyl.

11. The connection of claim 10, where R4means 2,4-disubstituted or 2,4,6-triple-substituted phenyl.

12. The connection of claim 10, where R2means of CH3and R4means of 2-bromo-4-isopropylphenyl.

13. The connection section 12, selected from the group comprising (2-bromo-4-isopropylphenyl)-[8-(1-ethylpropyl)-4-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-yl]amine,

(2-bromo-4-isopropylphenyl)ethyl[8-(1-ethylpropyl)-4-methyl-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-yl]amine,

(2-bromo-4-isopropylphenyl)-[4-methyl-8-(1-propinball)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-yl]amine and

(2-bromo-4-isopropylphenyl)ethyl[4-methyl-8-(1-propinball)-5,6,7,8-tetrahydropyrido[2,3-d]pyrimidine-2-yl]amine, as well as their acid additive salts with hydrochloric acid.

14. The compound according to claim 2, where n is 2, R1means

(1) a branched or unbranched1-C10alkyl, or

(2) optionally substituted heteroaryl(C1-C6)alkyl, where the specified heteroaryl optionally substituted Deputy selected from the group comprising C1-C3alkyl,

(3) optionally substituted phenyl, and specified phenyl optionally substituted by a Deputy selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen,

(4) C1 -C3alkyl, substituted phenyl group, and specified phenyl optionally substituted by a Deputy selected from the group comprising C1-C3alkyl, C1-C3alkoxy and halogen,

R3means hydrogen, C1-C6alkyl or benzyl,

R4means optionally substituted phenyl.

15. The connection 14, where R4means 2,4-disubstituted or 2,4,6-triple-substituted phenyl.

16. The connection indicated in paragraph 15, where X1means (CH2)n, n is 2, R2means of CH3, R3means of CH2CH3and R4means 2,4,6-triple-substituted phenyl.

17. Connection P16 selected from the group including (9-cyclohexylmethyl-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl(9-furan-2-ylmethyl-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)amine,

ethyl(9-indan-1-yl-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)amine,

ethyl(4-methyl-9-thiophene-2-ylmethyl-6,7,8,9-tetrahydro-5H-pyrimido [4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)amine,

ethyl(4-methyl-9-pyridine-3-ylmethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)amine,

[9-(1,2-diphenylether)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl[9-(2-methoxy-1-mutilat the l)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

ethyl[4-methyl-9-(1-methyl-3-phenylpropyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

ethyl[9-(1-ethylpropyl)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

(9-benzyl-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)ethyl(2,4,6-trimetilfenil)amine,

[9-(2,4-dichlorobenzyl)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl[9-(3-terbisil)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

ethyl[4-methyl-9-(2-phenylpropyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine, ethyl(4-methyl-9-phenethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)Amin, (9-allyl-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)ethyl(2,4,6-trimetilfenil)amine, ethyl(4-methyl-9-pentyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-9-(1-propinball)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

(9-cyclopropylmethyl-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-9-(1-phenylpropyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

ethyl{9-[1-(4-forfinal)ethyl]-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl}(2,4,6-trimetilfenil)amine,

[9-(2,4-d is chloro-6-methylbenzyl)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl]ethyl(2,4,6-trimetilfenil)amine,

ethyl[4-methyl-9-(2-phenoxyethyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

ethyl[4-methyl-9-(3-propoxyphenyl)-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl](2,4,6-trimetilfenil)amine,

[9-(2,4-dimetilfenil)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl]ethyl(2,4,6-trimetilfenil)amine,

[9-(2,4-dimethylbenzyl)-4-methyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl]ethyl(2,4,6-trimetilfenil)amine and

(4-methyl-9-thiophene-2-ylmethyl-6,7,8,9-tetrahydro-5H-pyrimido[4,5-b]azepin-2-yl)(2,4,6-trimetilfenil)amine, as well as their acid additive salts with triperoxonane acid.

18. The compound according to any one of claims 1 to 17, as well as its pharmaceutically acceptable salts intended for the preparation of drugs for treatment or prevention of disorders mediated by CRF receptor.

19. Drug with activity against CRF containing one or more compounds according to any one of claims 1 to 17 and pharmaceutically acceptable excipients, and intended for the treatment and prevention of disorders mediated by CRF.



 

Same patents:

FIELD: medicine; pharmacology.

SUBSTANCE: new discovered pyrimidine compounds of formula where R1-R9 are those as specified are selective inhibitors of group Src of nonreceptor tyrosine kinases. These compounds and their pharmaceutically acceptable salts are antiproliferative agents applied for treatment and fight against solid tumours, specifically breast tumours, rectum tumours, liver and pancreatic tumours.

EFFECT: applicable for cancer treatment.

17 cl, 5 dwg, 16 ex, 1 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to new condensed derivatives of azolpyrimidine of formula (I), their tautomeric or stereoisomeric form and their physiologically accepted salts. Compounds of this invention have improved activity of phosphatidyl inositol-3-kinase (P13K) inhibiting, specifically of P13K-γ inhibiting, and can be applied for production of medicinal agents for prevention and treatment of P13K- and P13K-γ activity based diseases. Those diseases are inflammatory and immunoregulatory diseases such as asthma and others. In compounds of formula (I) . X means CR5R6 or NH; Y1 means CR3 or N; chemical bond between means single bond or double bond, as long as means double bond, then Y2 and Y3 mean CH, and as long as mean single bond, then Y2 and Y3 mean regardless CR3R4; Z1, Z2, Z3 and Z4 mean redardless CH , CR2 or N; R1 means phenyl, optionally containing 1 to 3 substitutes selected from group including R11, C3-8cycloalkyl, optionally containing 1 to 3 substitutes selected from group including R11, C1-6alkyl, optionally containing as substitutes one or more halogen atoms, or 3-15-component mono- or bicyclic heterocyclic ring being saturated or non-saturated, optionally containing 1 to 3 substitutes selected from group including R11, and containing 1 to 3 heteroatoms selected from group including N, O and S, where R11 means halogen, nitro-, hydroxyl-, cyano-, carboxy-, amino-, N-(C1-6alkyl)amino-, K-(hydroxyC1-6alkyl)amino-, N,N-di(C1-6alkyl)amino-, N(C1-6acyl)amino-, N-(formyl)-N-(C1-6 alkyl) amino-, N-(C1-6alkansulphonyl)amino-, N-(carboxy C1-6 alkyl)-N-(C1-6 alkyl) amino-, N-(C1-6 alkansulphonyl)amino-, N-[N,N-di(C1.6 alkyl)aminomethylene] amino-, N-[N,N-di(C1-6 alkyl)amino(C1-6 alkyl)methylene]amino-, N-[N,N-di(C1-6 alkyl)aminoC1-6alkenyl]amides, aminocarbonyl, N-(C1-6 alkyl)aminocarbonyl, N,N-di(C1-6 alkyl)aminocarbonyl, C3-8 cycloalkyl, C1-6alkylthio, C1-6 alkansulphonyl, sulphamoyl, C1-6alkoxycarbonyl, phenylC1-6alkoxycarbonyl, where specified phenylic fragment optionally contains 1 to 3 substitutes selected from group including R101, C1-6alkyl, optionally containing as substitutes 1, 2 or 3 halogen atoms, C1-6alkoxy, optionally containing as substitutes 1, 2 or 3 halogen atoms, or 5- 7-component saturated or non-saturated ring containing 1 to 3 heteroatoms selected from group containing N, and optionally containing 1 to 3 substitutes selected from group including and R101, where R101 means halogen, carboxy, amino-, N-(C1-6alkyl)amino-, N,N-di(C1-6alkyl)amino-, aminocarbonyl, N-(C1-6alkyl)aminocarbonyl, N,N-di(C1-6alkyl)aminocarbonyl, C1-6alkyl, and C1-6alkoxy; R2 mean hydroxy, halogen, nitro-, cyano-, amino-, N-(C1-6alkyl)amino-, N,N-di(C1-6alkyl)amino-, N-(hydroxyC1-6alkyl)amino-, N-(hydroxyC1-6alkyl)-N-(C1-6alkyl)amino-, C1-6 acoxy, aminoC1-6 acoxy, C2-6alkenyl, phenyl, 5-7-compound saturated or non-saturated heterocyclic ring containing 1 to 2 heteroatoms selected from group including O and N, and optionally containing as substitutes: hydrohy, d-balkyl, N-(C1-6acyl)amino-, phenyl, phenylC1-6alkyl, C1-6alkyl, optionally containing as substitutes R21, or C1-6alkoxy, optionally containing as substitutes R21, where R21 means cyano group, 1, 2 or3 halogen atoms, hydroxy, amino-, N-(C1-6alkyl)amino-, N,N-di(C1-6alkyl)amino-, C1-6alkoxy, hydroxyC1-6alkoxy, -C(O)-R201, -NHC(O)-R201, C3-8 cycloalkyl, phthalymidil, 2-oxo-1,3-oxazolidinyl, phenyl or 5- or 6-compound saturated or non-saturated heterocyclic ring containing 1 to 4 heteroatoms selected from group including O and N, and optionally containing as substitutes hydroxy, C1-6alkyl, N-(C1-6acyl)amides or benzyl, where R201 means hydroxyl, amino-, N-(C1-6alkyl)amino-, N,N-di(C1-6alkyl)amino-, N-(halogenphenylC1-6 alkyl)amides, C1-6alkyl, aminoC1-6alkyl, C1-6alkoxy, 5- or 6-compound saturated or non-saturated heterocyclic ring containing 1 to 2 heteroatoms selected from group including O and N; R3 means hydrogen, halogen, aminocarbonyl or C1-6alkyl, optionally containing as substitutes phenylC1-6alkoxy or 1, 2 or 3 halogen atoms; R4 means hydrogen or C1-6alkyl; R5 means hydrogen or C1-6alkyl; and R means halogen, hydrogen or C1-6alkyl. Invention also refers to medicinal agent, inhibition method and compound application.

EFFECT: compounds under this invention have improved activity.

16 cl, 2 tbl, 18 ex

Asaindoles // 2326880

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to pharmaceutical formulation inhibiting protein kinase, containing inhibiting selective kinase compound amount of general formula (I): , where: R means aryl or indolyl, and the latter is optionally substituted with one or more groups selected from R4, -C(=O)-R, -C(=O)-OR5, -C(=O)-NY1Y2 and -Z2R; R2 means H; R3 means H; R4 means C1-C6 alkyl, optionally substituted with one substitute -C(=O)-NY1Y2; R5 means H; R7 means C1-C6 alkyl; R means C1-C6 alkyl; X1 means C-aryl, C-heteroaryl, such as pyridile or isoxasolyl, and the latter is optionally substituted with one or two C1-C6 alkyls, C-heterocycloalkyl, such as morpholinile or peperidynil, C-halogen, C-CN, C-OH, C-Z2R, C-C(=O)-OR5, C-NYlY2, C-C(=O)-NY1Y2; Y1 and Y2 means redardless H, aryl, C3-C6 cycloaryl, C1-C6 alkyl, optionally substituted with one group selected from phenyl, halogen, heterocyclil, such as morpholinile, phurile, hydroxyl, -C(=O)-OR5, OR7; or group-NY1Y2 can form morpholinile, peperidynil, optionally substituted with one or two substitutes selected from OH, C1-C6 alkyl; Z means O; where aryl as group or part of group means optionally substituted with one or two substitutes monocyclic aromatic C6carbocyclic fragment, where substitute is selected from halogen or C1-C6 alkoxy, C(=O)-OR5; except compounds: 4-chlorine-2-(4-tert-butylphenyl)-1H-pyrrole[2,3-b]pyridine, 2-(5-methoxy-1 -methyl-1 H-indole-3-il)-4-phenyl-1H- pyrrole[2,3-b]pyridine, 2-(5- methoxy-1 -methyl-1 H-indole-3-il)-1H- pyrrole[2,3-b] pyridine-4-carbonitrile, 4-chlorine-2-(5- methoxy-1 -methyl-1H-indole-3-il)-1H- pyrrole[2,3-b]pyridine, or 2-(5- methoxy-1H-indole-3-il)-1H- pyrrole[2,3-b]pyridine -4- carbonitrile.

EFFECT: application of compound for production of medicinal agent for inflammatory disease.

51 cl, 9 tbl, 148 ex

FIELD: chemistry.

SUBSTANCE: described is the compound of the general formula , where R1, R2, R3, R4, R5, R6, R7, R8 can be identical or different represent independently hydrogen, halogen, percahalogenalkyl, (C1-C3)alkyl or (C1-C3)alkoxy; R9, R10, R11, R12 R13 and R14 can be identical or different and represent independently hydrogen or (C1-C3)alkyl; "n" is equal to 1 or 2, it is preferable that n be equal to 1; not obligatorily R13 and R14 together with nitrogen atom cab form a 6- term heterocyclic ring, where heterocycle can also be substituted by (C1-C3)alkyl that can have "additional heretoatoms", selected from N and O. Described also are intermediate compounds, the method of their production, pharmaceutical composition and the use of pharmaceuticals intended for treatment of the cases when modulation of the 5-HT receptor activity.

EFFECT: compounds as per this invention are applicable in treatment of disturbances of nervous system.

16 cl, 34 ex

FIELD: medicine; pharmacology.

SUBSTANCE: this invention describes new crystal forms of tryazol[4,5-d]pyrimidine formula I , composition methods and based pharmaceutical formulations. Compounds develop high efficiency as antagonist P2T, can be applied for medical prevention and treatment of arterial thrombotic complication, as well as tumour growth and extension.

EFFECT: compounds show high metabolic stability and bioavailability.

22 cl, 5 ex, 6 dwg

FIELD: chemistry.

SUBSTANCE: invention refers to organic substances production and can be applied for production of herbicides and other bioactive compounds. Production of 2-sulphanilamine-1,2,4-triazolo[1,5-a]pyrimidine of general formula , where R1 is metal, phenylic, 4-methyl phenylic, 4-chlorophenylic group, R is phenylic, 4-methyl phenylic, 4-chlorophenylic, methoxyphenylic group, R is metal, phenylic, 4-methyl phenylic, 4-chlorophenylic group is sulphurization of 2-amino-4,7-dihydro-1,2,4-triazolo [1,5-a]pyrimidines (II) by sulphochlorides (III) in pyrimidine and oxidation of produced 2-sulphanilamine-4,7-dihydro-1,2,4-triazolo[1,5-a] pyrimidines (IV) by bromine in acetic acid with sodium acetate occurrence.

EFFECT: method allows to produce compounds using low-price and reasonable raw materials without any complicated processing steps applied.

1 cl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to synthesis of heterocyclic compounds, which contain pyrrolo[1,2-а][1,4]diazepine fragment, annelated to aromatic and heteroaromatic ring. Method for preparation of derivatives of pyrrolo[1,2-а][1,4]diazepine of general formula I, where А =

, is described. The said derivatives may be of use as substances with potential CNS activity, or with analgesic, antimicrobial and antifungal effect. Method implies recyclization of furan ring of 5-methyl-furfurylamides of general formula 2, , where А stands for above shown groups, by exposure to temperature of 60-70°С in the mixture of glacial acetic acid and strong hydrochloric acid in volumetric ratio 1:0.15 for 10-15 minutes.

EFFECT: provides for simultaneous formation of pyrrole and diazepine rings and improves yield of end products due to less number of process steps.

FIELD: organic chemistry, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to compounds of the general formula (I): wherein R1 represents (C1-C4)-alkyl with branched or linear chain; R2 represents hydrogen atom (H); R3 represents (C1-C4)-alkyl with branched or linear chain; R4 represents (C1-C4)-alkyl with branched or linear chain, (C2-C4)-alkenyl; R5 represents -SO2NR10R11; R8 represents (C1-C4)-alkyl with branched or linear chain; each R10 and R11 represents independently H or (C1-C12)-alkyl with branched or linear chain; or R10 and R11 in common with nitrogen atom to which they are bound form pyrrolinone group, piperidyl, morpholinyl, 4-N(R13)-piperazinyl that are substituted optionally with (C1-C4)-alkyl with branched or linear chain, -NR14R15, phenyl group substituted optionally with -OH or phenyl group bound in common with other substituted phenyl group by carbonyl group; R13 represents (C1-C4)-alkyl with branched or linear chain, (C2-C6)-alkyl with branched or linear chain and substituted with hydroxyl; (C2-C6)-alkyl with branched or linear chain substituted with phenyl; (C2-C6)-hydrocarbon with branched or linear chain substituted with -CO2R8; wherein each radical among R14 and R15 represents independently H; (C1-C4)-alkyl with branched or linear chain, or its pharmaceutically acceptable salt. The claimed compounds possess inhibitory effect on activity of phosphodiesterase-5 and can be used for production of drug for treatment or prophylaxis of diseases associated with phospholipase and its function. Also, invention relates to pharmaceutical composition, medicinal composition for veterinary science, and intermediate compounds IA-IG used for synthesis of compound of the formula (I).

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

8 cl, 2 tbl, 4 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the general formula (I): wherein R1 is chosen from group consisting of hydrogen atom (H), -(CH2)3-, -(CH2)4-, -CH2-S-CH2-, -S-CH2-CH2-; R2 is chosen from group consisting of nitrogen (N), sulfur (S) atom; n = 0 or 1; Z is chosen from group consisting of (C2-C10)-alkyl; R3 is chosen from group consisting of H; m = 0-2; R4 is chosen from group consisting of oxygen atom (O), -CH2-; R5 is chosen from group consisting of the following groups:

wherein R6 is chosen from group consisting of H, alkyl-(C1-C5)-alkoxyl; W is chosen from group consisting of -NH wherein each "alkyl" can be linear or branched and can be also cyclic or linear, or branched and comprises such cyclic residues, and each "aryl" comprises monocyclic aromatic group comprising 5-12 carbon atoms bound with one or some heteroatoms chosen from N, O or S atoms, and to their salts and solvates. Also, invention relates to a pharmaceutical composition, to a method for their synthesis and using compounds by claims 1-6. Invention provides synthesis of novel active compounds and pharmaceutical compositions based on thereof that possess affinity to serotonin receptors of subtype 5-HT1A.

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

10 cl, 4 tbl, 26 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention describes compound of the general formula (I): wherein R0 represents hydrogen atom; R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11 and R12 can be similar or different and each represents independently hydrogen atom, halogen atom, perhalogenalkyl, substituted or unsubstituted groups, such as linear or branched (C1-C12)-alkyl, (C3-C7)-cyclaoalkyl, (C1-C12)-alkoxy, cyclo-(C3-C7)-alkoxy group, hydroxyalkyl; R13 and R14 can be similar or different and each represents independently hydrogen atom, substituted or unsubstituted groups, such as linear or branched (C1-C4)-alkyl, (C3-C7)-cycloalkyl, optionally, R13 and R14 in common with nitrogen atom can form 5-6-membered heterocyclic ring wherein heterocycle can be substituted also, and it can comprise one, two or three double bonds or "additional heteroatoms" chosen from nitrogen atom (N); "n" means a whole number in the range 1-6, and pharmaceutical compositions based on its. Indicated compounds are ligands of 5-HT (serotonin) and can be used in treatment in cases if modulation of activity of 5-HT and melatonin is desirable.

EFFECT: valuable medicinal properties of compounds and pharmaceutical compositions.

21 cl, 31 ex

FIELD: chemistry.

SUBSTANCE: compounds with the formula are described and its pharmaceutically acceptable salts, where Y, Z, R1, R2, R3, R4, R5, R6, R7, R8, R9, m, n, p and q are as specified in the invention. The obtained compounds have the modulating activity regarding the 5-HT receptors. The pharmaceutical composition which contains the compounds with formula (I) and used in treatment of certain central nervous system diseases is also described.

EFFECT: novel compound group with useful biological properties is obtained.

10 cl, 2 dwg, 7 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to multicorpuscular dosed composition with regulated release of lamotrigin or its pharmaceutically acceptable salt, presented as tablet or capsule containing (a) composition nucleus particles, containing lamitrigin within dosage range 25 to 600 mg; (b) specified composition nucleus particles coated with polymer regulating release rate; and (c) quick-breaking vehicle enabling particles to disperse in aqueous environment, yet specified vehicle is taken in amount 1% to 10% of composition total, and specified dosed composition is characterised with specific release profile. Besides, invention refers to production of specified composition, as well as to application and therapeutic methods for CNS disorders by this composition.

EFFECT: improved therapeutic conditions and schedule.

28 cl, 14 tbl, 12 ex

FIELD: chemistry; medicine.

SUBSTANCE: invention pertains to derivatives of 7-phenylpyrazolopyridine with formula (I) ,where R1, R5, R6, R40, R41 and R42 represent different hydrocarbon substitutes or functional groups, its salts or hydrates, and especially to salts of N-cyclopropylmethyl-N-7-[2,6-dimethoxy-4-(methoxymethyl)phenyl]-2-ethylpyrazolo[1,5-a]pyradin-3-yl-N-tetrahydro-2H-4-pyranylmethylamine. The compound with formula (I), especially salts of N-cyclopropylmethyl-N-7-[2,6-dimethoxy-4-(methoxymethyl)phenyl]-2-ethylpyrazolo[1,5-a]pyradin-3-yl-N-tetrahydro-2H-4-pyranylmethylamine, act as antagonists of the receptor of corticotrophin release factor and can be used in medicine for treating various diseases of the nervous system and the gastrointestinal tract.

EFFECT: obtaining of new biologically active substances.

162 ex, 5 tbl

FIELD: chemistry; obtaining of medicinal preparations.

SUBSTANCE: description is given of a compound with general formula where R1 represents a halogen, C1-C6alkyl, CF3, CF2H or cyano, R2 represents C1-C6alkyl, R3 represents 5- or 6 - member hetero-aryl, optionally substituted with one, two or three substitutes, chosen from a group, consisting of a halogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkylhalogen, C1-C6alkoxy, NR'R", or substituted with a 1-morpholinyl group or substituted with thiomorpholinyl groups, 1-oxothiomorpholinyl or 1,1-dioxothiomorpholinyl; R', R" independently represent hydrogen, C1-C6alkyl, (CH2)0,1-(C3-C6)cycloalkyl, R represents hydrogen as well as its pharmaceutical salts and the method of obtaining them. The invention also relates to use of the given amidazole derivatives for obtaining medicinal preparations and to medicinal preparations containing them, meant for prevention or treatment of damages, through the mGluR5 receptor, such as acute and/or chronic neurologic damages, primarily shock pain, or for treatment of chronic and sharp pain.

EFFECT: obtaining of new compounds, with useful biological properties.

40 ex

FIELD: chemistry; obtaining of medicinal preparations.

SUBSTANCE: description is given of a compound with general formula where R1 represents a halogen, C1-C6alkyl, CF3, CF2H or cyano, R2 represents C1-C6alkyl, R3 represents 5- or 6 - member hetero-aryl, optionally substituted with one, two or three substitutes, chosen from a group, consisting of a halogen, C1-C6alkyl, C3-C6cycloalkyl, C1-C6alkylhalogen, C1-C6alkoxy, NR'R", or substituted with a 1-morpholinyl group or substituted with thiomorpholinyl groups, 1-oxothiomorpholinyl or 1,1-dioxothiomorpholinyl; R', R" independently represent hydrogen, C1-C6alkyl, (CH2)0,1-(C3-C6)cycloalkyl, R represents hydrogen as well as its pharmaceutical salts and the method of obtaining them. The invention also relates to use of the given amidazole derivatives for obtaining medicinal preparations and to medicinal preparations containing them, meant for prevention or treatment of damages, through the mGluR5 receptor, such as acute and/or chronic neurologic damages, primarily shock pain, or for treatment of chronic and sharp pain.

EFFECT: obtaining of new compounds, with useful biological properties.

40 ex

Compounds // 2327690

FIELD: chemistry.

SUBSTANCE: description is given of compounds with formula (I) in which A and B represent -(CH2)m- and -(CH2)n- groups respectively; R1 represents hydrogen or C1-6 alkyl; R2 represents hydrogen, C1-6alkyl, C1-6alkoxy, -S-C1-6alkyl, -(CH2)pNR5R6 optionally substituted aryl, heteroaryl or optionally substituted heterocyclyl; R3 represents optionally substituted aryl or optionally substituted heteroaryl; R4 represents hydrogen, C1-6alkyl or halogen; R5 and R6 each independently represents hydrogen or C1-6akyl; Z represents -(CH2)rX-, in which the -(CH2)r- group is bonded to R3 radical, or -X(CH2)r-, in which X is bonded to R3 radical; X represents oxygen, -NR7 group or -CH2- group; R7 represents hydrogen or C1-6alkyl; m and n independently represent an integer, chosen from 1 and 2; p represents 0; r independently represents an integer, chosen from 0 and 1. The invention also relates to use of the given compounds in therapy, in particular, as antipsychotic agents. The result is achieved when using serotonin receptors 5-HT2c, 5-HT2A and 5-HT6.

EFFECT: given compounds have antagonist affinity to serotonin receptors.

12 cl, 9 tbl, 265 ex

FIELD: organic chemistry.

SUBSTANCE: description is given of compounds with formula (I) and their pharmaceutical salts, in which n, X, Y, R1, R2, R3, R4 and R5 are defined in this invention. The obtained compounds have modulating action relative to "5-НТ6" receptors. Description is also given of a pharmaceutical composition based on compounds with formula (I), used as "5-НТ6" modulators for treating damages to the central nervous system.

EFFECT: obtaining of new compounds, with useful biological properties.

10 cl, 1 tbl, 5 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention refers to methods of self-specific T-cell vaccine production. Self-specific T-cell vaccine for disseminated sclerosis treatment includes attenuated T-cells which are reactive relative to one or several epitopes, yet SEQ ID NOS: 1-6 contain these epitopes. Invention is intended for treatment of autoimmune diseases, such as disseminated sclerosis or rheumatoid arthritis using self-specific T-cell vaccines. Besides, invention provides diagnostics of diseases associated with T-cells. Advantage of this invention implies that it can be applied for production of T-call vaccines with heterogenous gene VR-Dp-JR to take into consideration clonal shift if self-reactive T-cells.

EFFECT: method has improved efficiency.

10 cl, 7 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: composition for treatment of postintoxicational state and alcoholic abstinence syndrome-hangover, produced as powder mixture for drinking, contains concentrates of cabbage and sorrel, extracts of licorice root and vine crowns, succinic and ascorbic acids, premix with vitamins added, sodium glutaminate, as well as extracts of spice-aromatic plants: dill, cloves, coriander, garlic, bayberry and allspice, laurel and dried dill, sugar and salt taken in specified proportion. The second version of composition for treatment of postintoxicational state and alcoholic abstinence syndrome-hangover, produced as powder mixture for drinking, contains concentrates of salted cucumber and sorrel, extracts of licorice root and vine crowns, citric, succinic and ascorbic acids, premix, sodium glutaminate, as well as extracts of spices, dill, cloves, coriander, garlic, bayberry and allspice, laurel and dried dill, sugar and salt taken in specified proportion.. Offered method of treatment of postintoxicational state and alcoholic abstinence syndrome-hangover includes application of specified agents as powder for drinking at a rate one pack of composition containing 16.055 g and 10.555 g respectively per 200-250 ml of water.

EFFECT: composition application provides evident clinical effect.

3 cl, 9 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: touch-and-heal herb (Hypericum perforatum L.) is extracted. Ethyl alcohol concentrated within 60...90% is used as extracting agent. Raw material and extracting agents are taken in proportion as follows 1:11 ÷ 1:13.

EFFECT: invention enables to carry out specified value and increase flavonoid yield.

8 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: 2 blood samples are taken with interval 3 days against complex medicinal supplement under the following scheme. Therapy of the first exfusion day is characterized with single introduction of phetabolyl 0.4 mg/kg intramuscularly, 5% vitamin B1 - 50 mg intravenously, vitamin B12 - 500γ st. units intramuscularly, 5%vitamin C - 150 mg intravenously and 10 % aminoplasmal E - 250 ml intravenously drop-by-drop. The same day and the next two days imply intramuscular injection of ferrum lek 100 mg once, sorbypher 325 mg twice a day, folic acid - 5 mg 3 times a day. For the second day exfusion is accompanying with single subcutaneous introduction of epocryne in dosage 4 thausand UNITS. Then for the third day control inspection is carried out. The second day of exfusion implies single introduction of 5% vitamin B6 - 50 mg intravenously, 5% vitamin C - 150 mg intravenously, vitamin B12 - 500γ st.units intramuscularly and 10% aminoplasmal E - 250 ml intravenously drop-by-drop. This day and in the subsequent two - three days imply intramuscular introduction of ferrum lek 100 mg once, sorbypher 325 mg twice a day, folic acid - 5 mg 3 times a day. For the second day exfusion is accompanying with single subcutaneous introduction of epocryne in dosage 4 thausand UNITS. Then for the third day control inspection is carried out again. Since the first exfusion and before autoblood preparation nutritive supplement is carried out using module protein added to mix "Berlamine Modular" 50 g twice a day daily. After exfusion autoblood is divided on erythrocyte mass and fresh frozen plasma.

EFFECT: prevention of dangerous erythropoiesis and metabolic disorders.

1 ex, 3 cl

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