Carbonyl compounds

FIELD: chemistry, pharmacology.

SUBSTANCE: claimed invention relates to novel compounds of general formula(I) , where D represents phenyl, pyridyl or tienyl, each of which is single-substituted or double-substituted with Hal; R1 represents H, =O, COOR3, OH, OA, NH2, alkyl, which has 1, 2, 3, 4, 5 or 6 carbon atoms, N3, ethinyl, vinyl, allyloxy, -OCOR3, NHCOA or NHSO2A; R2 represents H, =O, OH, OA or alkyl, which has 1, 2, 3, 4, 5 or 6 carbon atoms; R1 and R2 together alternatively represent spirocyclically linked 3-6-member carbocyclic ring, R3 represents H or A, R4 represents H or A; represents pyrrolidine-1,2-diyl, piperidine-1,2-diyl, oxazolidine-3,4 or 3,5-diyl, thiazolidine-3,4-diyl, 2,5-dihydro-1H-pyrrol-1,5-diyl, 1,3-dioxolane-4,5-diyl; G represents (CH2)n or (CH2)nNH-; X represents CONH; Y represents 1,3- or 1,4-phenylene, which is not substituted or is single-substituted with methyl, trifluoromethyl, ethyl, propyl, Cl or F; T represents morpholine-4-yl, which is single-substituted or double-substituted with carbonyl oxygen; A represents non-branched or branched alkyl, which has 1-10 carbon atoms and in which 1-7 hydrogen atoms can be substituted with F; Hal represents F, CI, Br or I, n represents 0, 1 or 2; and their pharmaceutically acceptable derivatives, solvates, salts or sterioisomers, including their mixtures in all ratios. Invention also relates to method of obtaining formula I compounds, to medication based on formula I compound and application of formula I compounds for preparation of medication, which has inhibiting activity with respect to coagulation factors Xa and VIla.

EFFECT: obtained novel compounds have inhibiting activity with respect to said coagulation factors.

11 cl, 1 tbl, 14 ex

 

The text descriptions are given in facsimile form.

1. The compounds of formula I

in which D represents a phenyl, pyridyl or thienyl, each of which odnosnie or Duhalde Hal

R1represents H, =O, COOR3HE, OA, NH2, alkyl which has 1, 2, 3, 4, 5 or 6 carbon atoms, N3ethinyl, vinyl, allyloxy, -OCOR3, NHCOA or NHSO2A,

R2represents H, =O, HE, OA or alkyl which has 1, 2, 3, 4, 5 or 6 carbon atoms,

R1and R2together alternative represent spiral ligeski associated 3-6-membered carbocyclic ring,

R3represents H or A,

R4represents H or A,

is pyrrolidin-1,2-diyl, piperidine-1,2-diyl, oxazolidine-3,4 - or 3,5-diyl, thiazolidin-3,4-diyl, 2,5-dihydro-1H-pyrrol-1,diyl, 1,3-dioxolane-4,5-diyl,

G represents (CH2)nor (CH2)nNH-,

X represents CONH,

Y is 1,3 - or 1,4-phenylene, which is unsubstituted or odnosnie or Duhalde the stands, trifluoromethyl, ethyl, propylene, Cl or F,

T represents morpholine-4-yl, which odnosnie or Duhalde carbonyl oxygen,

And represents an unbranched or branched alkyl that has 1 to 10 carbon atoms and in which 1-7 h atoms may be replaced by F,

Hal represents F, Cl, Br or I,

n represents 0, 1 or 2;

and their pharmaceutically usable derivative, solvate, salt, and stereoisomers, including mixtures thereof in all respects.

2. Compounds according to claim 1, selected from the group including:

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(R)-pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(R)-pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(R)-pyrrolidin-1,2-what carboxamid,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(R)-pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-trifluoromethyl-4-(3-exmortis-4-yl)-phenyl]}-(R)-pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(R)-2,5-dihydropyrrol-1,2-dicarboxamide,

N-[4-(3-exmortis-4-yl)phenyl]-(R)-1-(5-chlorothiophene-2-carbonyl)pyrrolidin-2-carboxamid,

N-[3-methyl-4-(3-exmortis-4-yl)phenyl]-(R)-1-(5-chlorothiophene-2-carbonyl)pyrrolidin-2-carboxamid,

3-N-[(4-chlorophenyl)]-4-N-{[4-(3-exmortis-4-yl)phenyl]}-(R)-oxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(R)-oxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[4-(3-exmortis-4-yl)phenyl]}-(4R,5S)-5-methyloxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)-4-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(4R,5S)-5-methyloxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[3-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(4R,5S)-5-methyloxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[3-chloro-4-(3-exmortis-4-yl)-phenyl]}-(4R,5S)-5-methyloxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(4R,5R)-5-methyloxazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[4-(3-exmortis-4-yl)phenyl]}-(S)-thiazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[4-(3-exmortis-4-yl)phenyl]}-S)-1,1-dioxo-1λ 6-thiazolidin-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(S)-thiazolidine-3,4-dicarboxamide,

3-N-[(4-chlorophenyl)]-4-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(S)-1,1-dioxo-1λ6-thiazolidin-3,4-dicarboxamide,

N-[4-(3-exmortis-4-yl)phenyl]-3-(5-chlorothiophene-2-carbonyl)-oxazolidin-5-carboxamid,

N-[3-methyl-4-(3-exmortis-4-yl)phenyl]-3-(5-chlorothiophene-2-carbonyl)-oxazolidin-5-carboxamid,

1-N-[(5-chloropyridin-2-yl)]-2-N-{[4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(5-chloropyridin-2-yl)]-2-N-{[4-(3-exmortis-4-yl)-phenyl]}-(R)-4,4-dimethoxypyrimidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,3R)-3-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,3S)-3-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-yl)phenyl]}-(2S,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-3,4-dihydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-azidopyridine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-aminopyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-azidopyridine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-aminopyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-acetaminophenramadol-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-acetaminophenramadol-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-methylsulfonylamino-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-methylsulfonylamino-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-proximinality-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-alliancebernstein-1,2-dicarboxamide,

(3R,5R)-1-(4-who hlorfenilovy)-5-[4-(3-exmortis-4-yl)phenylcarbamoyl]pyrrolidine-3-yl isobutyrate,

(3R,5R)-1-(4-chlorpheniramol)-5-[4-(3-exmortis-4-yl)phenylcarbamoyl]pyrrolidine-3-yl propionate,

(3R,5R)-1-(4-chlorpheniramol)-5-[4-(3-exmortis-4-yl)phenylcarbamoyl]pyrrolidine-3-yl acetate

4-N-[(4-chlorophenyl)]-5-N-{[4-(3-exmortis-4-yl)phenyl]}-1,3-dioxolane-4,5-dicarboxamide,

4-N-[(4-chlorophenyl)]-5-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-1,3-dioxolane-4,5-dicarboxamide,

4-N-[(4-chlorophenyl)]-5-{[4-(3-exmortis-4-yl)phenyl]}-1,3-dioxolane-2,2-dimethyl-4,5-dicarboxamide,

4-N-[(4-chlorophenyl)]-5-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-1,3-dioxolane-2,2-dimethyl-4,5-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-ethinyl-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(2R,4S)-4-acetaminophenramadol-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-butylmethylamine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(R)-4-oxopyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(2R,4S)-4-aminopyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(S)-pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

N-[4-(3-about somerton-4-yl)phenyl]-(2R,4R)-1-[2-(4-chlorophenyl)acetyl]-4-hydroxypyrrolidine-2-carboxamide,

N-[4-(3-exmortis-4-yl)phenyl]-(2R,4R)-1-(4-chlorobenzoyl)-4-hydroxypyrrolidine-2-carboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4S)-4-(2-methylpropylamine)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

2-N-[(4-chlorophenyl)]-1-N-{[4-(3-exmortis-4-yl)phenyl]}-(R)-pyrrolidin-1,2-dicarboxamide,

2-N-[(4-chlorophenyl)]-1-N-{[4-(3-exmortis-4-yl)phenyl]}-(S)-pyrrolidin-1,2-dicarboxamide,

N-(4-chlorophenyl)-(R)-1-{2-[4-(3-exmortis-4-yl)phenyl]-acetyl}-pyrrolidin-2-carboxamid,

N-(4-chlorophenyl)-(S)-1-{2-[4-(3-exmortis-4-yl)phenyl]-acetyl}-pyrrolidin-2-carboxamid,

N-(4-chlorophenyl)-(2R,4R)-1-{2-[4-(3-exmortis-4-yl)-phenyl]acetyl}-4-ethoxypyrrolidine-2-carboxamid,

N-(4-chlorophenyl)-(2R,4S)-1-(2-[4-(3-exmortis-4-yl)-phenyl]acetyl}-4-ethoxypyrrolidine-2-carboxamid,

N-(4-chlorophenyl)-(2S,4R)-1-{2-[4-(3-exmortis-4-yl)-phenyl]acetyl}-4-ethoxypyrrolidine-2-carboxamid,

1-N-[(4-chlorophenyl)]-2-N-{[4-(2-oxo-2H-p the Razin-1-yl)phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(prop-2-ynyloxy)pyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(but-2-ynyloxy)pyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(2,3-dihydroxypropane)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(2-hydroxy-3-pyrrolidin-1 ipropose)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(3-amino-2-hydroxypropoxy)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[3-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(R)-2,5-dihydropyrrol-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(R)-2,5-dihydropyrrol-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2S,3S)-3-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2S,4S)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-carboxy-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-3-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,3S,4R)-3,4-dihydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N - {[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-alliancebernstein-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-(prop-2-ynyloxy)pyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4S)-4-(prop-2-ynyloxy)pyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(ethoxycarbonylmethoxy)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(carboxymethoxy)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-bromophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-ethoxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-fluoro-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-(2,3-dihydroxypropane)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-aminocarbonyl-4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide;

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxy-2-methylpyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-3-N-{[4-(3-exmortis-4-yl)phenyl]}-piperidine-1,3-dicarboxamide,

1-N-[(4-chlorophenyl)]-3-N-{[3-methyl-4-(3-exmortis-4-yl)-phenyl]}piperidine-1,3-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-(2-methoxyethoxy)pyrrolidin-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-methyl-4-(3-exmortis-4-yl)-phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

1-N-[(4-chlorophenyl)]-2-N-{[2-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide,

and their pharmaceutically usable derivative, solvate, salt, and stereoisomers, including mixtures thereof in all ratios.

3. Method of producing compounds of the formula I according to claims 1 and 2 and their

pharmaceutically usable derivatives, solvate, salts and stereoisomers, which is characterized by the fact that

to obtain compounds of the formula I, in which

W represents N and

G represents NH,

the compound of formula II

in which R1, R2, E, X, Y and T have the meanings indicated in claim 1,

and W represents N,

subjected to interaction with the compound of the formula III

in which D has the meanings indicated in claim 1,

and/or a base or acid of the formula I is converted into one of its salts.

4. The compounds of formula I according to claim 1 or 2, as inhibitors of coagulation factor XA.

5. The compounds of formula I according to claim 1 or 2, as inhibitors of coagulation factor VIIa.

6. Drug, possess inhibitory activity against coagulation factor XA and VII, which contains at least one compound of formula I according to claim 1 or 2, and/or its pharmaceutically prydnyeproskaya, the solvate, salts and stereoisomers, including mixtures thereof in all ratios, and optionally excipients and/or auxiliary substances.

7. The use of compounds according to claim 1 or 2, and/or their physiologically acceptable salts and solvate for the preparation of drugs for the treatment of thrombosis, myocardial infarction, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after plastic surgery on the blood vessels moving claudication, migraine, tumours, tumour diseases and/or tumor metastasis.

8. The use of compounds of the formula I according to claim 1 or 2, and/or pharmaceutically usable derivatives, solvate, salts and stereoisomers, including mixtures thereof in all ratios, for the preparation of drugs for the treatment of thrombosis, myocardial infarction, arteriosclerosis, inflammation, apoplexy, angina pectoris, restenosis after plastic surgery on the blood vessels moving claudication, migraine, tumours, tumour diseases and/or tumor metastases in combination with aspirin.

9. Intermediate compounds selected from the group including:

N-[4-(3-exmortis-4-yl)phenyl]-(S)-pyrrolidin-2-carboxamid,

N-[4-(3-exmortis-4-yl)phenyl]-(R)-pyrrolidin-2-carboxamid,

N-[4-(3-exmortis-4-yl)phenyl]-(2R,4R)-4-hydroxypyrrolidine-2-carboxamide,

N-[4-(3-exmortis-4-yl)phenyl]-(R)-4,4-methoxypyridine-2-carboxamide,

and their isomers and salts.

10. Drug, possess inhibitory activity against coagulation factor XA and VIIa containing 1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxy-pyrrolidine-1,2-dicarboxamide and/or pharmaceutically usable derivative, solvate, salt, and stereoisomers, including mixtures thereof in all ratios, and aspirin.

11. The use of claim 8 1-N-[(4-chlorophenyl)]-2-N-{[4-(3-exmortis-4-yl)phenyl]}-(2R,4R)-4-hydroxypyrrolidine-1,2-dicarboxamide and/or pharmaceutically usable derivative, solvate, salt, and stereoisomers, including mixtures thereof in all ratios, in combination with aspirin.



 

Same patents:

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I) , where R1 represents phenyl group, containing 1-3 substitutes, selected from halogen and cyano group; R2 represents pyridyl group, which has 1-3 substitutes, selected from monocyclic or polycyclic heterocyclic group, which can have 1-3 substitutes, selected from halogen atoms, cyanogroup, as well as other values of R2 radical, given in formula of invention, R3 represents phenyl group or pyridyl group, which has 1-2 substitutes, selected from halogen and trihalogenmethyl group; R4 represents hydrogen atom; and X represents -SO2-; its salt or its solvate. As well as to medication and pharmaceutical composition, inhibiting production or secretion of β-amyloid protein, and containing compound of formula (I), and to application of compound of pt.1 in order to obtain medication.

EFFECT: obtaining novel compounds, inhibiting production or secretion of β-amyloid protein.

14 cl, 1 tbl, 296 ex

FIELD: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. The compounds claimed by the invention have inhibition effect on VR1 receptor activation and can be applied in pain prevention or treatment. In the general formula (I) , or , L is a low alkylene, E cycle is benzene or 5-membered heteroaromatic ring containing sulfur atom as a heteroatom, D cycle is a monocyclic or bicyclic hydrocarbon cycle optionally condensed with C5-7 cycloalkyl, 6-membered monocyclic heteroaromatic cycle containing nitrogen atom as heteroatom or 9-11-membered bicyclic heteroaromatic cycle containing 1 to 3 equal or different heteroatoms selected out of the group including N, S and O, G cycle is a 5-7-membered monocyclic saturated or partially saturated heterocycle or 10-membered bicyclic heterocycle containing 1 to 3 equal or different heteroatoms selected out of the group including N, S and O. The invention also concerns pharmaceutical composition based on the said compounds, and application thereof in obtaining pain prevention or treatment medication, and a method of pain prevention or treatment.

EFFECT: obtaining prevention or treatment medium against pain.

24 cl, 470 ex, 41 tbl

FIELD: medicine; pharmacology.

SUBSTANCE: derivatives possess antiproliferative activity and stimulate an apoptosis in cells where absence of normal regulation of development of a cell and its destruction is observed. The derivatives are applied as a part of pharmaceutical compositions in combination with pharmaceutically acceptable mediums. The pharmaceutical compositions can be applied for treatment of diseases caused by hyperproliferation, including tumour growth, lymphoproliterative diseases and angiogenesis. Invention compounds pertain to the group of replaced pyrazoles and Pyrazolinums characterised by the formula of the invention.

EFFECT: derivatives possess useful biological properties.

56 cl, 115 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to the obtaining of the new derivatives of benzamide of the formulas (I), which possess the activating influence on glucokinase, which can be used for treating of diabetes and obesity: where X1 and X2 represent oxygen, R1 represents alkylsufonyl, alkaneyl, halogen or hydroxyl; R2 represents alkyl or alkenyl, R3 represents alkyl or hydroxyalkyl, ring A represents phenyl or pyridyl, the ring B represents thiazolyl, thiadiazolil, isoxazoleyl, pyridothiazolyl or pyrazolyl, in which the atom of carbon of ring B, which is connected with the atom of nitrogen of the amide group of the formula(I), forms C=N bond with ring B.

EFFECT: obtaining new bioactive benzamides.

12 cl, 166 ex, 4 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to new pyrimidine of the general formula (I), which possess properties of the inhibitor of CDK-kinase. In the general formula (I) R1 designates hydrogen, halogen, C1-C6alkyl, R2 designates C1-C10alkyl, C1-C10alkenyl, or C3-C10cycloalkyl which can be mono-, bi- or tricyclic or denotes one- or polysubstituted by identical or different substitutes from the number of hydroxy-group, halogen, C1-C6alkoxygroup, C1-C6kalkylthiogroup, -NH-(CH2)n-C3-C10cycloalkyl, C3-C10 cycloalkyl, C1-C6hydroxyalkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkoxy-C1-C6alkyl, -NHC1-C6alkyl, -N(C1-C6alkyl)2, C1-C6alkanoil, -CONR3R4, -COR5, C1-C6alkylOAc, where Ac indicates C1-C4alkylCO-group, carboxygroups, phenyl, 5-6-member heteroaryl, containing 1-2-heteroatom in the ring, selected from nitrogen, -(CH2)n- phenyl, -(CH2)n-5-6-member heteroaryl containing 1-2-heteroatom in a ring, selected from nitrogen, phenyl-(CH2)n-R5, -(CH2)nPO3(R5)2 and -R6 and -NR3R4C1-C10alkyl, or C3-C10cycloalkyl, in this case phenyl, C3-C10 cycloalkyl, heteroaryl, -(CH2)n-phenyl and -(CH2)n heteroaryl can be one or polysubstituted by identical or different substitutes from halogens, hydroxygroup, C1-C6alkyl, C1-C6alkoxygroup, benzoxy-group and -CF3 groups, and ring of C3-C10 cycloalkyl and C1-C10alkyl can be separated by one or several nitrogen atoms, oxygen and/or sulfur and/or the said ring can be interrupted by one or two groups of =C=O or R2 designates the group X designates oxygen or group-NH-, and one of A and B independently indicates hydrogen, and the other indicates hydrogen, hydroxygroup, C1-C3alkyl, C1-C6alkyoxy,group SR7, SO2R7, CO(OH)R7, CR7(OH)R7, C1-C6alkyl-P(O)OR3OR4, COR7 or A and B together form C3-6-cycloalkyl ring which does not necessarily have to be interrupted by 1-3 atoms of nitrogen, oxygen and/or sulfur and/or can be interrupted by =C=O or =SO2 groups, and/or does not necessarily have to contain one or several double bonds, X designates oxygen or group-NH-, either one from A and B independently indicates hydrogen, and the other indicates hydrogen, hydroxygroup, C1-C3alkyl, C1-C6alkyoxy,group SR7, SO2R7, CO(OH)R7, CR7(OH)R7, C1-C6alkyl-P(O)OR3OR4, COR7 or A and B together form C3-6-cycloalkyl ring which does not necessarily have to be interrupted by 1-3 atoms of nitrogen, oxygen and/or sulfur and/or can be interrupted by =C=O or =SO2 groups, and/or does not necessarily have to contain one or several double bonds, values of R3 -R10 are specified in the formula of the invention.

EFFECT: connections can be used for the treatment of cancer, autoimmune diseases caused by chemotherapeutic means of alopecia and inflammations of mucous membrane, cardiovascular diseases, infectious diseases, chronic neurodegenerative and viral infections.

13 cl, 1 tbl, 540 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the compounds of the formula (I) where: X is O; Y represents a bond, CH2, NR35, CH2NH, CH2NHC(O), CH(OH), CH(NHC(O)R33), CH(NHS(O)2R34), CH2O or CH2S; Z is C(O), or if Y is a bond, then Z can also be S(O)2; R1 could be substituted with phenyl; R4 is hydrogen, C1-6-alkyl (substituted possibly by C3-6-pilkoalkyl) or C3-6-cycloalkyl; R2, R3, R5, R6, R7 and R8 are independently hydrogen, C1-6-alkyl or C3-6-cycloalkyl; type independently indicate 0 or 1; R9 could possibly be substituted with an aryl or heterocycle; R10, R32 and R35 are independently hydrogen, C1-6-alkyl or C3-6-cycloalkyl; R33 and R34 are C1-6-alkyl or C3-6-cycloalkyl; where the aforesaid aryl and heterocyclic groups, when possible, can be substitute with: halogen cyanogens, nitro, hydroxyl, oxo, S(O)Kr12, OC(O)NR13R14, NR15R16, NR17C(O)R18, NR19C(O)NR20R21, S(O)2NR22R23, NR24S(O)2R25, C(O)NR26R27, C(O)R28, CO2R29, NR30CO2R31, by C1-6-alkyl (which itself can be monosubstituted with NHC(O)phenyl), C1-6-halogenalkyl, C1-6-alkoxy(C1-6)alkyl, C1-6-alkoxy, C1-6-halogenaloxy, C1-6-alkoxy(C1-6)-alkoxy, C1-6-alkylthio, C2-6-alkenyl, C2-6-alkinil, C3-10-cycloalkyl, methylenedioxy, difluoromethylenedioxy, phenyl, phenyl(C1-4)alkyl, phenoxy, phenylthio, phenyl(C1-4)alkyl, morpholinyl, heteroaryl, heteroaryl(C1-4)alkyl, heteroarylhydroxy of heteroaryl(C1-4)alkoxy, where any of the said phenyl and heteroaryl groups can be substituted by halogen, hydroxyl, nitro, S(O)r(C1-4-alkyl), S(O)2NH2, S(O)2NH(C1-4-alkyl), S(O)2N(C1-.4-alkyl)2, cyanogens, C1-4-alkyl, C1-4-alkoxy, C(O)NH2, C(O)NH(C1-4-alkyl), CO2H, CO2(C1-4-alkyl), NHC(O)( C1-4-alkyl), NHS(O)2(C1-4-alkyl), C(O)( C1-4-alkyl), CF3 or OCF3; k and r independently mean 0, 1 or 2; R13, R14, R15, R16, R17, R18, R19, R20, R21, R22, R23, R24, R26, R27, R29 and R30 independently represent hydrogen, C1-6-alkyl (probably replaced by halogen, hydroxyl or C3-10-cycloalkyl), CH2(C2-6-alkenyl), C3-6-cycloalkyl, phenyl (itself probably replaced by halogen, hydroxyl, nitro, NH2, NH(C1-4-alkyl), NH(C1-4-alkyl)2, S(O)2(C1-4-alkyl), S(O)2NH2, S(O)2NH(C1-4-alkyl), S(O)2N(C1-4-alkyl)2, cyanogen, C1-4-alkyl, C1-4-alkoxy, C(O)NH2, C(O)NH(C1-4-alkyl), C(O)N(C1-4-alkyl)2, CO2H, CO2(C1-4-alkyl), NHC(O)(C1-4-alkyl), NHS(O)2(C1-4-alkyl), C(O)(C1-4-alkyl), CF3 or OCF3) or heterocyclyl (itself probably replaced by halogen, hydroxyl, nitro, NH2, NH(C1-4-alkyl), N(C1-4-alkyl)2, S(O)2)(C1-4-alkyl), S(O)2NH2, S(O)2NH(C1-4-alkyl), S(O)2N(C1-4-alkyl)2, cyanogen, C1-4-alkyl, C1-4-alkoxy, C(O)NH2, C(O)NH(C1-4-alkyl), C(O)N(C1-4-alkyl)2, CO2H5 CO2(C1-4-alkyl), NHC(O)( C1-4-alkyl), NHS(O)2(C1-4-alkyl), C(O)( C1-4-alkyl), CF3 or OCF3); alternatively, NR13R14, NR15R16, NR20R21, NR22R23, NR26R27 can independently form 4-7-member heterocyclic ring, selected from the group, which includes: azetidine (which can be substituted by hydroxyl or C1-4-alkyl), pyrrolidine, piperidine, azepine, 1,4-morpholine or 1,4-piperazine, the latter is probably substituted by C1-4-alkyl on the peripheral nitrogen; R12, R25, R28 and R31 are independently C1-6-alkyl (possibly substituted by halogen, hydroxyl or C3-10-cycloalkyl), CH2(C2-6-alkenyl), phenyl (itself probably replaced by halogen, hydroxyl, nitro, NH2, NH(C1-4- alkyl), N(C1-4-alkyl)2, (and these alkyl groups can connect to form a ring as described hereabove for R13 and R14), S(O)2(C1-4-alkyl), S(O)2NH2, S(O)2NH(C1-4-alkyl), S(O)2N(C1-4-alkyl)2 (and these alkyl groups can connec to form a ring as described hereabove for R13 and R14), cyanogen, C1-4- alkyl, C1-4- alkoxy, C(O)NH2, C(O)NH(C1-4- alkyl), C(O)N(C1-4-alkyl)2 (and these alkyl groups can connect to form a ring as described hereabove for R13 and R14), CO2H, CO2(C1-4-alkyl), NHC(O)(C1-4-alkyl), NHS(O)2(C1-4-alkyl), C(O)(C1-4-alkyl), NHC(O)(C1-4-alkyl), CF3 or OCF3) or heterocyclyl (itself probably replaced by halogen, hydroxyl, nitro, NH2, NH(C1-4-alkyl), N(C1-4-alkyl)2, (and these alkyl groups can connect to form a ring as described hereabove for R13 and R14), S(O)2(C1-4-alkyl), S(O)2NH2, S(O)2NH(C1-4-alkyl), S(O)2N(C1-4-alkyl)2 (and these alkyl groups can connect to form a ring as described hereabove for R13 and R14), cyanogen, C1-4-alkyl, C1-4-alkoxy, C(O)NH2, C(O)NH(C1-4- alkyl), C(O)N(C1-4-alkyl)2 (and these alkyl groups can connect to form a ring as described hereabove for R13 and R14), CO2H, CO2(C1-4-alkyl), NHC(O)(C1-4-alkyl), NHS(O)2(C1-4-alkyl), C(O)(C1-4-alkyl), CF3 or OCF3); or its N-oxide; or its pharmaceutically acceptable salt, solvate or solvate of its salt, which are modulators of activity of chemokines (especially CCR3); also described is the pharmaceutical composition on their basis and the method of treating the chemokines mediated painful condition.

EFFECT: obtaining new compounds possessing useful biological properties.

13 cl, 238 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention concerns applications of compositions formulated as follows or its salt, solvate or prodrug of medical agent for treatment or prevention of disease state mediated by glucokinase (GLK). Besides, given invention concerns new group of composition formulated as (I) and to method of specified compositions production. The invention enables to widen range of agents used for treatment or prevention of disease conditions mediated by glucokinase (GLK) where each of R1, R2, R3, n and m has values specified in the description.

EFFECT: increased efficiency.

19 cl, 51 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention is related to the compounds of general formula (I) and their pharmaceutically acceptable salts with properties β2-adrenoreceptor agonists, to the method of their production and based on them pharmaceutical composition. The compounds can be used for treatment of conditions when the symptomatic severity can be reduced by β2- adrenoreceptor activation, e.g., obstructive or inflammatory respiratory diseases. In the general formula (I) , X means -R1-Ar-R2 or -Ra-Y; Ar means phenylen, optionally substituted by group of the row: halogen, hydroxy, C1-C10alkyl, C1-C10alcoxy, phenyl, C1-C10 alcoxy, substituted by phenyl group or phenyl, substituted by C1-C10 alcoxy group; R1 and R2 are bound to the adjacent carbon atoms within Ar group, and either R1 means C1-C10alkylen, and R2 means hydrogen, C1-C10alkyl or halogen, Ra means the bond or C1-C10 alkylen optionally substituted by group of the row: hydroxy, C1-C10 alcoxy, C6-C10aryl or C7-C14aralkyl; Y means C1-C10alkyl, or C2-C10alkynil, optionally substituted by hydroxyl group, C3-C10cycloalkyl, optionally condensed with one or more benzene rings and optionally substituted by group of the row: C1-C10alkyl, C1-C10alcoxy, C3-C10cycloalkyl, C7-C14aralkyl, C7-C14aralkyloxy or C6-C10aryl, where groups C7-C14aralkyl, C7-C14aralkyloxy or C6-C10 aryl are optionally substituted by group of the row: halogen, C1-C10alkyl, C1-C10alcoxy; C6-C10aryl, optionally substituted by group of the row: halogen, hydroxy, C1-C10alkyl, C1-C10alcoxy, C1-C10halogenalkyl, phenoxy, C1-C10alkylthio, C6-C10aryl, 5-6-term saturated heterocyclic ring, containing one nitrogen atom in cycle; phenoxy, optionally substituted by C1-C10alcoxy group; 5-6-term heterocyclic ring, containing one or two nitrogen or oxygen atoms in cycle, and the described heterocyclic ring is optionally substituted by group of the row: C1-C10alkyl, C6-C10aryl, C7-C14aralkyl, C1-C10alcoxycarbonil or 5-7-term heterocyclil (C1-C10)alkyl, containing one nitrogen atom in cycle; -NRdRe, where Rd means hydrogen or C1-C10alkyl, and Re means C1-C10alkyl, or Re means C6-C10aryl, or Re means 5-6-term heterocyclic ring, containing one nitrogen or sulfur atom in cycle, and the ring is optionally substituted by halogen-substituted phenyl group or Re means C6-C10arylsypfonil, optionally substituted by groups C1-C10alkylamino or di(C1-C10alkyl)amino; -SRf, where Rf means C6-C10aryl or C7-C14aralkyl, optionally substituted by group of row: halogen or C1-C10halogenalkyl; or -CONHRg, where Rg means C6-C10aryl, provided, if Ra means the bond, then Y doesn't mean C1-C5alkyl.

EFFECT: compound can prevent or reduce symptom's intensity.

15 cl, 4 tbl, 157 ex

FIELD: medicine; pharmacology.

SUBSTANCE: invention relates to the novel compounds with formula (I) and their pharmaceutically acceptable salts. The compounds of this invention has the properties of the NPY receptor antagonists and can be used fortreatment of such diseases as arthritis, diabetes, malnutrition, obesity. In general formula (I) , R1 means phenyl or 6-term nitrogen-containing heteroaryl, where in at least one of two meta-positions each phenyl group or 6-term nitrogen-containing heteroaryl group is substituted by group R5; R2 means hydrogen; R3 means C3-C6cycloalkyl, naphthyl, phenyl or 5-6-term heteroaryl, containing N or S as heteroatoms, where in at least one of two ortho-positions each group of C3-C6 cycloalkyl, naphthyl, phenyl or 5-6-term heteroaryl, containing N or S as heteroatoms, substituted by group R6; R4 means hydrogen, C1-C6alkyl; R5 means hydrogen, cyano, trifluoromethyl, C1-C6alkyl-SO2-, amino-SO2-, halogen, C1-C6alcoxy, C1-C6alkylcarbonil or aminocarbonil; R6 means hydrogen, halogen, cyano, nitro, trifluoromethyl, C1-C6 alkyl, C1-C6 alcoxy or hydroxy, provided, one R5 group, and R6 doesn't mean hydrogen.

EFFECT: described compounds and based on them pharmaceutical agents are efficient in treatment and prevention of above listed diseases.

19 cl, 2 tbl, 2 dwg, 130 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

FIELD: chemistry.

SUBSTANCE: invention refers to benzothiazole derivatives of general formula I and to their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands and based medicinal product. Compounds can be applied for treatment and prevention of diseases mediated by adenosine receptors, e.g., epilepsy, depressions, narcomania, Parkinson's disease. In general formula I R denotes phenyl unsubstituted or substituted with halogen or -SN2N(CH3) (CH2)nOCH3, or denotes benzyl, lower alkyl, lower alkoxy-group, - (CH2)nOCH3, or denotes pyridine-3- or -4-yl unsubstituted or substituted with lower alkyl, halogen, morpholinyl, - (CH2)n-halogen, - (CH2)nOCH3, - (CH2)n-diethylene-imide oxide-4-yl, or (CH2)n-tetrahydropyrrole-1-yl; R1 denotes phenyl unsubstituted or substituted with halogen tetrahydropyran-4-yl, 3,6-2H-2n-pyran-4-yl or morpholine-4-yl; n denotes mutually independent 1 or 2.

EFFECT: production of benzothiazole derivatives which can be applied for treatment and prevention of diseases mediated by adenosine receptors.

9 cl, 4 dwg, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the new compounds presented by the following formula (I), or to the pharmaceutically acceptable salts: , where R1 and R2 represent substitutes, adjoining with each other and with two carbonic atoms, to each of which they are adjoined forming the group presented by the following formula: 1) , or

2) , , , , , , , , or

3) or

4) , , or

where hydrogen atom in each cyclic group can be substituted bi 1-4 substitutes selected fro the following group of substitutes B1, R3 represents hydrogen atom or methyl group; and R6 represents substitute selected from the following group of A1 substitutes, the group of A1 substitutes: (1) hydrogen atom, (2) C1-C6 alkoxy group; substitute B1 group: (1) hydrogen atom, (2) hydroxyl group, (3) oxo group, (4) C1-C6 alkanoyl group, (5) C3-C8 cycloalkyl group, (6) C1-C6 alkyl group (where C1-C6 alkyl group can be substituted by C1-C6 alkoxy group), (7) C1-C6 alkoxy group, (8) C1-C6 alkoxyimino group, (9) C5-C6 cycloalkyl group, derived by two C1-C3 alkyl groups joined to the same carbonic atom with hydrogen atom and the carbons. The invention is also relates to the pharmaceutical composition.

EFFECT: production of the new biologically active compounds and pharmaceutical compositions on their basis having inhibitor potency towards to serotonine1A receptor.

34 cl, 73 ex, 12 tbl, 4 dwg

FIELD: chemistry, pharmaceuticals.

SUBSTANCE: invention pertains to compounds with formula (I), their pharmaceutical salts or N-oxide used as an inhibitor to replication and/or proliferation of HCV, to the method of inhibiting replication or proliferation of hepatitis C virion using formula (I) compounds, as well as to pharmaceutical compositions based on them. The compounds can be used for treating or preventing infections, caused by hepatitis C virus. In general formula (I) cycle B is an aromatic or non-aromatic ring, which contains two heteroatoms, where X and Y, each is independently chosen from C, CH, N or O, under the condition that, both X and Y are not O and that, both X and Y are not N; U and T represent C; Z represents -CH-; A represents N or -CR2-; B represents -CR3-; D represents N or -CR4-; E represents N or -CR5-; G represents N or -CR6-; J represents N or -CR14-; K represents -CR8-; L represents N or -CR9-; M represents N or -CR10-; R2 and R6, each is independently chosen from a group, consisting of hydrogen, halogen, C1-C6alkyl, substituted C1-C6alkyl, C1-C6alkoxy, C1-C6substituted alkoxy, C1-C6alkoxycarbonyl, cycloheteroalkyl, substituted cycloheteroalkyl, -O-carbamoil, substituted -O-carbamoil, halogen C1-C6alkyl, diC1-C6alkylamino, substituted diC1-C6alkylamino and sylye ethers, where cycloheteroalkyl is a 3-7-member ring, containing 1-2 heteroatoms, chosen from N and O, under the condition that, one of R2 and R6 is not hydrogen; R3 and R5, each is independently chosen from a group, consisting of hydrogen, halogen; R4 represents hydrogen; R7 represents - NR11C(O)R12; R8, R9, R10 and R14, each is independently represents hydrogen; R11 represents hydrogen, C1-C6alkyl; and R12 is chosen from a group, consisting of halogen C1-C6alkyl; where each substituted group is substituted with one or more groups, chosen from -Q, -R40, -OR40, -C(O)R40, -C(O)OR40, where each Q independently represents halogen, R40 and R41 are independently chosen from a group consisting of hydrogen, C1-C6alkyl, C1-C6alkoxy, under the condition that: (i) at least one of A, D, E, G, J, L or M represents N; (ii) not more than one of A, D, E or G represents N; and (iii) not more than one of J, L or M represents N.

EFFECT: obtaining pyridyl-substituted heterocycles for treating and preventing infections, caused by hepatitis C virus.

33 cl, 85 dwg, 101 ex

FIELD: chemistry.

SUBSTANCE: invention concerns compounds of the general formula: , where R1 is an inferior alkyl, -(CH2)n-aryl, unsubstituted or substituted by one or two substitutes from the group of inferior alkyl, inferior alkoxy-, halogen or trifluormethyl, or pyridine; R2 is an inferior alkyl, -(CH2)n- aryl, unsubstituted or substituted by one or two substitutes from the group of inferior alkyl, inferior alkoxy-, halogen or trifluoromethyl, nitro-, cyano-, -NR'R", hydroxy-, or heteroaryl group that is a monovalent heterocyclic 5- or 6-membered aromatic radical with N atoms, either R2 is a heteroaryl that is monovalent heterocyclic 5- or 6-membered aromatic radical where heteroatoms are chosen from N, O or S group, unsubstituted or substituted by one or two substitutes from the group of inferior alkyl or halogen; R3 is pyridine or aryl, unsubstituted or substituted by a halogen or inferior alkyl; R4 is hydrogen or hydroxy-. A is -S(O)2- or -C(O)-; X, Y are -CH2- or -O- independently from each other, though both X and Y should not be -O- at the same time; R'R" are hydrogen or inferior alkyl independently from each other; n is 0, 1 or 2. Also the invention concerns pharmaceutically acceptable additive salts and acids of the compounds, and a medicine based on it.

EFFECT: new biologically active compounds show inhibition effect in glycine absorption.

21 cl, 214 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to the new derivatives of imide indolylmaleic acid with the formula I , where Ra denotes H; C1-4alkyl or C1-4alkyl, with substituted OH, NH2, NH(C1-4 alkyl) or H(C1-4alkyl)2; Rb denotes H or C1-4alkyl; R denotes a radical of the formula (d) or (e) , where each one from R8 and R11 independently denotes OH; heterocyclic residue; NR16R17, where each from R16 and R17 independently denotes H or C1-4alkyl, or R16 and R17 together with a nitrogen atom; to which they are joined, form a heterocyclic residue; or a radical of the formula -X-RC-Y (α) where X denotes a covalent bond, O, S or NR18, where R18 denotes H or C1-4alkyl; Rc denotes C1-4alkylen or C1-4alkylen, in which one CH2 has been changed with the group CRxRy, whereby one of Rx and Ry denotes H, and the other denotes CH3, each of the Rx and Ry denote CH3 or Rx and Ry together form the group -CH2-CH2-, and Y is joined with the terminal carbon atom and is selected from OH, -NR19R20, where each one of R19 and R20 independently denotes C1-4alkyl; each one of R9, R10, R12, R13 independently denotes H, halogen, C1-4alkyl, OH, NH2, C1-4alkoxy, NH(C1-4alkyl) or N(C1-4alkyl)2 or each E denotes -N= and G denotes -CH= or E denotes -CH= and G denotes -N=, and cycle A is unsubstituted, monosubstituted, where the substitute is selected from a group containing halogen, OH, C1-4alkoxy, C1-4alkyl, NO2, NH2, NH(C1-4alkyl) or N(C1-4alkyl)2 or CN; where the heterocyclic residue is 3-8 member saturated, heterocyclic rings, containing 1-2-heteroatoms, of which one is N, and the other N or O, possibly substituted with one or more carbon atoms in the cycle and/or with a nitrogen atom in the cycle, if it is in the ring; where the substitutes of the carbon atom ring, if they exist, are selected from the group which contains C1-4alkyl, C3-C6cycloalkyl, it is optional to further substitute C1-4alkyl; , where p denotes 1, 2 or 3; and where the substitutes on the nitrogen atom ring if they exist, are selected from a group which contains C1-4alkyl, C3-C6cycloalkyl, C3-C6cycloalkyl C1-4alkyl, phenyl, phenylC1-4alkyl, heterocyclic residue and the residue from the formula β: -R21-Y' (β) R21 - denotes C1-C4alkylen, a Y' denotes OH, NH2, NH(C1-4alkyl) or N(C1-4alkyl)2, where the heterocyclic residue is of importance, as stated above, or its pharmaceutically acceptable salts.

EFFECT: bonds possess an action, which has an inhibitory activity on proteinkinase C and can be used in a pharmaceutical composition for treatment or prophylaxis of acute or chronic rejection of allo or xenotransilants of organs or tissues.

10 cl, 7 tbl, 182 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to derivatives of phtalazine with general formula (I) , in which R represents a methyl or difluromethyl group; R1 represents phenyl or oxazolyl or thiophenyl, chemically bonded to a phtalazine ring through a carbon-carbon bond. Both phenyl and the above mentioned heterocycle are substituted with a carboxylic group, and optionally with a second functional group, chosen from methoxy-, nitro-, N-acetylamino-, N-metanesulphonylamino- group. The invention also relates to pharmaceutical salts of such derivatives. The given compounds with general formula (I) are inhibitors of phosphodiesterase.

EFFECT: objective of the invention is also the method of obtaining compounds with general formula (I) and pharmaceutical compositions for treating allergies and antiphlogistic diseases based on the given compounds.

9 cl, 9 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new bonds in the formula (I-0): or its pharmaceutically acceptable salts, where X represents a carbon atom or nitrogen atom; X1, X2, X3 and X4, each independently, represents a carbon atom or a nitrogen atom; ring A of the formula (II): represents tiazolil, imidazolil, izotiazolil, tiadiazolil, triazolil, oxazolil, oxadiazolil, izoxazolil, pirazinil, piridil, piridazinil, pirazolil or pirimidinil; R¹ represents aryl or represents a 4-10- membered monocyclic or bicyclic heteroring, which has in the ring from 1 to 4 heteroatoms, selected from the group, consisting of a nitrogen atom, sulphur atom and an oxygen atom, and R¹ can be independently substituted with 1-3 R4, and, when the specified heteroring is an aliphatic heteroring, then it can have 1 or 2 double bonds; R² independently represents hydroxy, formyl, -CH3-aFa, -OCH3-aFa, amino, CN, halogen, C1-6 alkyl or -(CH2)1-4OH; R3 represents -C1-6 alkyl, -(CH2)1-6-OH, -C(O)-OC1-6 alkyl, -C(O)-OC1-6 alkyl, -(CH2)1-6-NH2, cyano, -C(O)-C1-6 alkyl, halogen, -C2-6 alkenyl, -OC1-6 alkyl, -COOH, -OH or oxo; R4 independently represents -C1-6 alkyl, and the alkyl can be substituted with identical or different 1-3 hydroxyls, halogens, -OC(O)-C1-6 alkyls, and the alkyl can be substituted with 1-3 halogens or -OC1-6 alkyls, -C3-7 cycloalkyl, -C2-6 alkenyl, -C(O)-N(R51)R52, -S(O)2-N(R51)R52,-O-C1-6 alkyl, and C1-6 alkylcan be substituted with a halogen or N(R51)R52, -S(O)0-2-C1-6 alkyl, -C(O)-C1-6 alkyl, and C1-6 alkyl can be substituted with a halogen, amino, CN, hydroxy, -O-C1-6 alkyl, -CH3-aFa, -OC(O)-C1-6 alkyl, -N(C1-6 alkyl)C(O)O-C1-6 alkyl, -NH-C(O)O-C1-6 alkyl, phenyl, -N(R51)R52, -NH-C(O)-C1-6 alkyl, -N(C1-6 alkyl)-C(O)-C1-6 alkyl or -NH-S(O)0-2-C1-6 alkyl, -C(S)-C3-7 cycloalkyl, -C(S)- C1-6 alkyl, -C(O)-O- C1-6 alkyl, -(CH2)0-4-N(R53)-C(O)-R54, -N(R53)-C(O)-O-R54,-C(O)-aryl, it is optional to substitute the halogen, -C(O)-aromatic heteroring, -C(O)-aliphatic heteroring, heteroring, and the heteroring can be substituted with C1-6 alkyl, optionally substituting the halogen or -O-C1-6 alkyl, phenyl, optionally substituting the halogen, -C1-6 alkyl, -O-C1-6 alkyl, halogen, CN, formyl, COOH, amino, oxo, hydroxy, hydroxyamidine or nitro; R51 and R52, each independently, represents a hydrogen atom, C1-6 alkyl or a nitrogen atom, R51 and R52 together form 4-7-member heteroring; R53 represents a hydrogen atom or C1-6 alkyl, R54 represents -C1-6 alkyl or alkyls for R53 and R54 and -N-C(O)- together form 4-7-member hydrogen containing heteroring, or alkyls for R53 and R54 and -N-C(O)-O- together form 4-7-member hydrogen containing aliphatic heteroring and an aliphatic heteroring can be substituted with oxo, or an aliphatic heteroring can have 1 or 2 double bonds in the ring; X5 represents -O-, -S-, -S(O)-, -S(O)2-, a single bond or -O-C1-6 alkyl; a independently denotes a whole number 1, 2 or 3; q denotes a whole number from 0 till 2; m denotes a whole number from 0 till 2, except in the case when one of the X5 represents -O-, -S-, -S(O)- or -S(O)2-, and the other from X5 represents a single bond, and R1 represents aryl, optionally substituted with 1-3 R4, or a hydrogen containing aromatic heteroring, consisting of from 1 to 4 heteroatoms, selected from the group, comprising of a hydrogen atom, sulphur atom and an oxygen atom, in the case, when X5, both represent single bonds or in cases, when R1, both represent aliphatic heteroring. The invention also relates to the bonding in the formula (I-12), and also to the bonding in the formula (I-0), to the pharmaceutical composition, to the glucokinase activator and to the medication.

EFFECT: getting new bioactive compounds which can be used for treatment and/or prophylaxis of diabetes or obesity.

23 cl, 603 ex

FIELD: chemistry.

SUBSTANCE: invention pertains to non-peptide antagonists GnRH, with general formula 1 , where each of A1, A2 and A3 are independently chosen from A5 and A6; and A4 represents either a covalent bond, or A5; under the condition that, if A4 is a covalent bond, then one of A1-A3 represent A6, and the other two represent A5, and that, if A4 represents A5, then all of A1-A3 represent A5; A5 is chosen from C-R13 and N; A6 is chosen from N-R14, S and O; R1 is chosen from H, NHY1 and COY2, and R2 represents H; or and R1, and R2 represents methyl or together represent =O; each of R3, R4 and R5 independently represents H or low alkyl; each of R6, R7, R8, R9, R10, R11 and R12 are independently chosen from H, NH2, F, CI, Br, O-alkyl and CH2NMe2; R13 is chosen from H, F, CI, Br, NO2, NH2, OH, Me, Et, OMe and NMe2; R14 is chosen from H, methyl and ethyl; W is chosen from CH and N; X is chosen from CH2, O and NH; Y1 is chosen from CO-low alkyl, CO(CH2)bY3, CO(CH2)bCOY3 and CO(CH2)bNHCOY3; Y2 is chosen from OR15, NRI6R17 and NH(CH2)cCOY3; Y3 is chosen from alkyl, OR15 and NR16R17; R15 represents H; each of R16 and R17 is independently chosen from H, low alkyl and (CH2)aR18, or together represent -(CH2)2-Z-(CH2)2-; R18 is chosen from OH, pyridyl, pyrizinyl and oxadiazolyl; Z represents NH; a represents 0-4; and b and c represent 1-3. The invention also relates to use of formula 1 a compound as a therapeutic agent and pharmaceutical composition, with antagonistic effect to GnRH receptor. Description is also given of the method of obtaining compounds with the given formula.

EFFECT: obtaining new compounds, with useful biological properties.

27 cl, 70 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new derivatives of benzimidazol of the general formula I R1 designates phenyl group which unessentially contains up to three substitutors independently chosen of the group including F, Cl, Br, J, R4; R2 designates monocyclic or bicyclic 5-10-terms heteroaryl group which contains 1-2 heteroatoms, chosen of N, S and O; R3 designates H; R4 designatesC1-6alkyl; A designates C2-6 alkylene group; B designates group COOH, CONH2, CONHR5 or CONR5R5, in each case attached to atom of carbon of group A; R5 and R5 ' independently designate the residue chosen from group includingC1-6 alkyl where one C-atom can be replaced by O, and(C0-3 alkandiil-C3-7 cycloalkyl); and to their pharmaceutically acceptable salts, except for following compounds: 6 [[1-phenyl-2 (pyridine-4-il)-1H-benzimidazol-6-il] oxi] hexanic acid and 6 [[1-phenyl-2 (benzothien-2-il)-1H-benzimidazol-6-il] oxi] hexanic acid. The invention relates also to pharmaceuticals and to application of compounds of general formula I.

EFFECT: new biologically active compounds possess inhibiting effect on activation of microglia.

10 cl, 34 ex

Amid derivative // 2336273

FIELD: chemistry.

SUBSTANCE: invention relates to amid derivatives of formula (I), method of disease treatment and pharmaceutical composition based on them. Compounds can be applied in treatment of different herpes virus infections. In general formula (I) , Z: 1,2,4-oxydiazol-3-yl, 4-oxazolyl, 1,2,3-triazol-2-yl or 2-pyridyl, A: phenyl, which can have a substitute (substitutes) selected from group, including lower alkyl, halogen, halogen-substituted lower alkyl, O-lower alkyl, O-lower alkylene -OH, CN, OH, O-lower alkylene-phenyl, O-lower alkylene-O-lower alkyl, NH2, NH-lower alkyl, N-(lower alkyl)2 ,NH-lower alkylene-OH, NH-lower alkylene-O-lower alkyl, O-lower alkylene- NH2, O-lower alkylene-NH-lower alkyl and O-lower alkylene-N(lower alkyl)2; heteroaryl, representing monocyclic 6-member ring, which contains nitrogen atom as heteroatom or bicyclic 9-member ring, containing 1-2 heteroatoms selected from nitrogen and/or sulfur, which can have a substitute (substitutes), selected from lower alkyl; or phenyl group, condensed with saturated 5-member hydrocarbon cycle; or phenyl group, condensed with saturated 5-member heterocyclic cycle, which contains 1-2 heteroatoms, selected from nitrogen and/or oxygen, which can have a substitute (substitutes), selected from group, including lower alkyl, halogen, -C(O)-lower alkyl, lower alkylene-O-lower alkyl, on condition, that aryl group, condensed with saturated hydrocarbon cycle or aryl group, condensed with saturated heterocyclic cycle is bound with nitrogen atom through carbon atom in aromatic cycle, X: CO, R3: C3-C6cycloalkyl, which can have a substitute (substitutes), selected from group, which includes oxo, OH, halogen, CN, O-lower alkyl, -C(O)-NH2, -C(O)-NH-lower alkyl, -C(O)-N(lower alkyl)2, lower alkylene-OH, lower alkylene-O-lower alkyl; aryl, selected from phenyl, naphtyl, which can have a substitute (substitutes), selected from halogen; pyridyl; 9-member bicyclic heteroaryl, containing 1-3 heteroatoms, selected from S, N, O; or saturated heterocyclic group, representing monocyclic 6-member group, which contains 1-2 heteroatoms selected from S, SO, SO2, N, O, which can have a substitute (substitutes), selected from halogen.

EFFECT: obtaining amid derivatives that can be applied for treating various herpes virus infections.

17 cl, 26 tbl, 125 ex

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