Triazolopyridazines as par1 inhibitors, production and use thereof as medicinal agents

FIELD: chemistry.

SUBSTANCE: described are novel triazolopyridazines of general formula , stereoisomeric or tautomeric forms thereof and physiologically acceptable salts thereof, where Q1 denotes H, -C1-6alkyl, optionally substituted with fluorine, or -C3-6cycloalkyl; Q2 and Q3 independently denote H, -C1-6alkyl; R1-R3 independently denote H, -C1-6 alkyl, -C3-6cycloalkyl, -O-C3-6cycloalkyl, -O-C1-8alkyl, a heterocyclic residue etc; R4-R8 independently denote H, -C1-6 alkyl, -OH, -O-C1-8 alkyl, halogen, SF5 etc, a method for production thereof and use as medicinal agents.

EFFECT: compounds have antithrombotic activity and particularly inhibit the protease-activated receptor.

6 cl, 2 tbl, 242 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):

and/or all stereoisomeric or tautomeric forms of the compounds of formula (I) and/or mixtures of these forms in any ratio, and/or a physiologically acceptable salt of the compounds of formula (I), where
Q1 means a hydrogen atom, -(C1-C6)-alkyl or -(C3-C6-cycloalkyl, where in the alkyl hydrogen atoms are wholly or partly can be replaced by fluorine;
Q2 and Q3 denote a hydrogen atom or -(C1-C6)-alkyl;
R1, R2 and R3 are the same or different and, independently of one another, mean a hydrogen atom, -(C1-C6)-alkyl, -(C3-C6-cycloalkyl, -O-(C1-C8)-alkyl, -O-(C3-C6-cycloalkyl -(C0-C4-alkylen-C(O)-N(R11)-R12, -(C0-C4-alkylene-N(R11)-R12, halogen, HE, -(C1-C6-alkylen-O-(C1-C6)-alkyl, -O-(C1-C6-alkylen-O-(C1-C6)-alkyl, -O-phenyl, -O-oxetanyl, -O-(C1-C4-alkylene - (C3-C6-cycloalkyl or heterocyclic residue selected from the group of piperidinyl, morpholinyl, imidazolyl and pyrazolyl,
where alkyl is nye, alkylene and cycloalkyl groups represented in the definitions of R1-R3 is not substituted, or one, or two, or three times, independently of one another, replaced by -(C1-C4)-alkyl, HE, -O-(C1-C6)-alkyl or oxetanyl where acetanilides the residue is not substituted or monoamide -(C1-C6)-alkyl; or
where in the alkyl, alkylene or cycloalkyl hydrogen atoms are wholly or partly can be replaced by fluorine;
provided that at least one of R1, R2 or R3 does not mean a hydrogen atom, or
R2 and R3 together with the atoms of the cycle with which they are linked, form a 5 - or 6-membered cycle, where a cycle consists only of carbon atoms;
R11 and R12, independently of one another, mean a hydrogen atom or -(C1-C6)-alkyl, where the alkyl hydrogen atoms are wholly or partly can be replaced by fluorine;
R4, R5, R6, R7 and R8 are the same or different and, independently of one another, mean a hydrogen atom, -(C1-C6)-alkyl, -HE,
-O-(C1-C8)-alkyl, halogen, -SF5-(C0-C4-alkylene-N(R21)-R22, -(C0-C4-alkylene-N(R21)-C(O)-R22, -(C1-C6-alkylen-O-(C1-C6)-alkyl, -(C0-C6-alkylen-O-(C1-C6-alkylen-O-(C1-C6)-alkyl, -(C0-C6-alkylen-O-(C1-C4-alkylene-(C3-C6-cycloalkyl or (C 0-C6-alkylen-O-(C0-C6-alkylen-phenyl,
where alkyl, Allenova and cycloalkyl group in the definitions of R4-R8, each substituted or one, two or three times, independently of one another, replaced by -(C1-C4)-alkyl, HE or-O-(C1-C6)-alkyl, or
where in the alkyl, alkylene or cycloalkyl hydrogen atoms are wholly or partly can be replaced by fluorine;
provided that at least one of R4, R5, R6, R7 or R8 does not mean a hydrogen atom, or
R6 and R7 or R7 and R8 together with the atoms of the cycle with which they are linked, form a 3,4-dihydro-2H-benzo[1,4]oxazino group;
where the cycle is not substituted or only once or twice, independently of one another, replaced by -(C1-C4)-alkyl;
R21 and R22, independently of one another, mean a hydrogen atom or -(C1-C6)-alkyl;
where in the alkyl hydrogen atoms are wholly or partly can be replaced by fluorine; or
R21 and R22 in the fragments of the "N(R21)-R22" means a cycle selected from the group pyrrolidinyl, piperidinyl, piperazinil, azepine, morpholine, thiomorpholine,
where the cycle is not substituted or mono-, or twice, independently of one another, replaced by -(C1-C4)-alkyl;

2. The compound of formula (I) according to claim 1, where
Q1, Q2 and Q3 are the same and signify a hydrogen atom,
R1, R2 and R3 are the same or different and follows the IMO from each other, means a hydrogen atom, -(C1-C6)-alkyl, -O-(C1-C8)-alkyl, -O-(C3-C6-cycloalkyl -(C0-C4-alkylen-C(O)-N(R11)-R12, -(C0-C4-alkylene-N(R11)-R12, halogen, -O-(C1-C6-alkylen-O-(C1-C6)-alkyl or-O-(C0-C4-alkylen-phenyl,
where the alkyl or alkylen, respectively, are not substituted or once or twice substituted-O-(C1-C6)-alkyl,
where in the alkyl or alkylene hydrogen atoms are wholly or partly can be replaced by fluorine;
provided that at least one of R1, R2 or R3 does not mean a hydrogen atom,
R11 and R12, independently of one another, mean a hydrogen atom or -(C1-C6)-alkyl;
R4, R5, R6, R7 and R8 are the same or different and, independently of one another, mean a hydrogen atom, -(C1-C6)-alkyl, HE, -O-(C1-C8)-alkyl, halogen, -SF5-(C0-C4-alkylene-N(R21)-R22, -(C0-C4-alkylene-N(R21)-C(O)-R22, -CF3-(C0-C6-alkylen-O-(C1-C6-alkylen-O-(C1-C6)-alkyl, -(C0-C6-alkylen-O-(C1-C4-alkylene-(C3-C6-cycloalkyl or -(C0-C6-alkylen-O-(C0-C6-alkylen-phenyl;
where the alkyl or alkylen, respectively, are not substituted or once or twice substituted-O-(C1-C6)-alkyl;
if h is about, at least one of R4, R5, R6, R7 or R8 does not mean a hydrogen atom; or
R6 and R7 together with the atoms of the cycle with which they are linked, form a 3,4-dihydro-2H-benzo[1,4]-oxazin;
where the cycle is not substituted or once or twice substituted by -(C1-C6)-alkyl;
R21 and R22, independently of one another, mean a hydrogen atom or -(C1-C6)-alkyl; or
R11 and R12 in the fragment of "N(R11)-R12" means a cycle selected from the group consisting of pyrrolidinyl, piperidinyl, piperazinil, azepine, imidazolyl, morpholinyl, thiomorpholine.

3. The compound of formula (I) according to claim 1, where the compound of formula (I) are selected from the group consisting of:
2-(6-chloro-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(3-imino-6-isopropoxy-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(3-imino-6-methoxy-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-(6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-(4-methoxy-3-morpholine-4-yl-5-triptoreline)ethanone;
N-[3-[2-(6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)acetyl]-5-(pentafluoroethyl)phenyl]-N-methylacetamide;
N-[3-[2-(6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)acetyl]-5-(pentafluoroethyl)phenyl]ndimethylacetamide;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-3-imino-[1,2,4]t is Iesolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-cyclopentyloxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-CYCLOBUTANE-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(3-imino-6-phenoxy-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-(6-benzyloxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-cyclohexyloxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[3-imino-6-(2,2,2-triptoreline)-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-cyclopropylmethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-methylamino-5-(pentafluoroethyl)-phenyl]ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-methoxy-5-(pentafluoroethyl)-phenyl]ethanone;
1-(3-tert-butyl-5-ethoxymethylene)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-cyclopropylacetylene)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]this is Nona;
1-(3-tert-butyl-4,5-dioxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-ethoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-propoxymethyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-4,5-bis-cyclopropylmethoxy)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-(3-methoxy-5-triptoreline)ethanone;
1-(3-tert-butyl-5-methoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-cyclopropylmethoxy)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-cyclobutylmethyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-benzoyloxymethyl-5-tert-butylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-cyclohexylmethoxy-4,5-acid)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
2-(6-butoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-(3-tert-butyl-5-methoxymethyl)ethanone;
1-(3-chloro-5-methoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(8-tert-butyl-4-methyl-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]what triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(3-imino-6-piperidine-1-yl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-diethylamino-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-(3-isopropyl-5-methoxyphenyl)ethanone;
1-(3-cyclohexylmethoxy-5-ethoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-bromo-5-methoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-[3-(3,3-Dimethylbutane)-5-methoxyphenyl]-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-[3-(3,3-Dimethylbutane)-5-ethoxyphenyl]-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-cyclohexylmethoxy-5-methoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-bromo-4,5-acid)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
2-(6-diethylamino-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(3-imino-6-morpholine-4-yl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-chloro-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-imidazol-1-yl-3-imino-[1,2,4]t is Iesolo[4,3-b]pyridazin-2-yl)ethanone;
1-(5-bromo-2,3-acid)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-methoxyphenyl)-2-{3-imino-6-[2-(2-methoxyethoxy)ethoxy]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}ethanone;
1-(3-chloro-4,5-acid)-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-diethylamino-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(2-methoxyethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-methoxyphenyl)-2-[3-imino-6-(2-methoxyethoxy)-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-methoxymethyl)-2-[3-imino-6-(2-methoxyethoxy)-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-morpholine-4-yl-5-(pentafluoroethyl)-phenyl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-(5-methoxy-3-pentafluoroethanesulfonyl)-ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-chloro-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(2-methoxyethoxymethyl)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]feast is disin-2-yl]-1-[3-(2-methoxyethoxy)-5-(pentafluoroethyl)-phenyl]ethanone;
2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
2-[6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-(3-methoxypropane)-5-(pentafluoroethyl)phenyl]ethanone;
the diethylamide 2-[2-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-oxoethyl]-6-chloro-3-imino-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-8-carboxylic acid;
the diethylamide 6-chloro-3-imino-2-{2-[3-methoxy-5-(pentafluoroethyl)phenyl]-2-oxoethyl}-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-8-carboxylic acid;
2-(6-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(3-methoxypropane)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-[3-tert-butyl-5-(2-methoxyethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-cyclopropylmethoxy)-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-methoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-[3-tert-butyl-5-(3-methoxypropane)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
2-(6-chloro-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]-feast is disin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]-ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-chloro-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
the diethylamide 6-chloro-3-imino-2-{2-[3-methoxy-5-(pentafluoroethyl)phenyl]-2-oxoethyl}-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-carboxylic acid;
the diethylamide 2-[2-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-oxoethyl]-6-chloro-3-imino-2,3-dihydro-[1,2,4]triazolo-[4,3-b]pyridazin-7-carboxylic acid;
1-[3-tert-butyl-5-(3-methoxypropane)phenyl]-2-(6-ethoxy-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-[3-tert-butyl-5-(2-methoxyethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
1-(3-tert-butyl-5-methoxyphenyl)-2-[6-(1-ethylpropoxy)-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
salt triperoxonane acid diethylamide 6 ethoxy-3-imino-2{2-[3-methoxy-5-(pentafluoroethyl)phenyl]-2-oxoethyl}-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-carboxylic acid;
salt triperoxonane acid 2-(3-imino-6-methoxy-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-chloro-7-diethylamino-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
salt triperoxonane acid 2-(6-chloro-7-diethylamino-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 2-(7-diethylamino-6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 2-[6-(1-ethylpropoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
salt triperoxonane acid diethylamide 2-[2-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-oxoethyl]-6-ethoxy-3-imino-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-7-carboxylic acid;
salt triperoxonane acid diethylamide 2-[2-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-oxoethyl]-6-ethoxy-3-imino-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-8-carboxylic acid;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]this is anhydroglucitol;
1-[3-tert-butyl-5-(3-methoxypropane)phenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
salt triperoxonane acid 1-[3-ethoxy-5-(pentafluoroethyl)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4] triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid diethylamide 6 ethoxy-3-imino-2-{2-[3-methoxy-5-(pentafluoroethyl)phenyl]-2-oxoethyl}-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-8-carboxylic acid;
salt triperoxonane acid 2-(3-imino-8-methyl-6-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(3-imino-8-methyl-6-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-b] pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxymethyl)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(3-imino-6-(2-methoxy-1-methoxymethylethoxy)-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-(3-imino-6-(2-methoxy-1-methoxymethylethoxy)-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-[6-(1-ethyl is repossi)-3-imino-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-methoxypropane)phenyl]-2-[6-(2-hydroxyethoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
salt triperoxonane acid 2-[6-((R)-sec-butoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 2-[6-((R)-sec-butoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)ethanone;
salt triperoxonane acid 2-[6-((S)-sec-butoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine-2-yl]economicrelated;
2-[6-((S)-sec-butoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-methoxy-5-(pentafluoroethyl)phenyl]economicrelated;
salt triperoxonane acid 2-(6-diethylamino-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 1-[3-ethoxy-5-(pentafluoroethyl)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]propane-1-it;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-(6-ethoxy-3-and the Ino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-(6-ethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-(6-ethoxy-3-imino-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine-2-yl)economicrelated;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
salt triperoxonane acid 2-(6,7-diethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-morpholine-4-yl-5-(pentafluoroethyl)phenyl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6,7-diethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-morpholine-4-yl-5-(pentafluoroethyl)-phenyl]economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo-[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]is talesin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl] economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-(3-tert-butyl-5-cyclopropylmethoxy)-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-methoxy-1-methoxymethylethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl] economicrelated;
1-[3-tert-butyl-5-(2-methoxy-1-methoxymethylethoxy)phenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-7,8,9,10-tetrahydro-[1,2,4]triazolo[3,4-a]phthalazine-2-yl)economicrelated;
salt triperoxonane acid 1-[3-ethoxy-5-pentafluoroethyl)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 2-[6-(1-ethylpropoxy)-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-is]-1-[3-morpholine-4-yl-5-(pentafluoroethyl)phenyl]ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-7,8-diethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-{6-ethoxy-7,8-dimethyl-3-[(E)-methyl-imino]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}ethanone;
1-[3-tert-butyl-5-(4-hydroxyethoxy)-4-methoxyphenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxymethyl)phenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(4-hydroxyethoxy)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-(3-tert-butyl-methoxy-5-morpholine-4-ylphenyl)-2-(7,8-dicyclopropyl-6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-3-imino-7,8-aminobutiramida-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[8-ethyl-6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-8-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[7,8-dicyclopropyl-6-(1-Etiler is poxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-7,8-aminobutiramida-[1,2,4] triazolo [4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[7,8-diethyl-6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[7-ethyl-6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-7-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[8-cyclopropyl-6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-8-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-{6-(1-ethylpropoxy)-7,8-dimethyl-3-[(E)-methylimino]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}-ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-diethylamino-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]is ridazin-2-yl)ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(8-cyclopropyl-6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-3-imino-8-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(3-hydroxy-2,2-DIMETHYLPROPANE)-4-methoxyphenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(3-hydroxy-2,2-DIMETHYLPROPANE)phenyl]-2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl] economicrelated;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-7-ethyl-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[7-cyclopropyl-6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[6-(1-ethylpropoxy)-3-imino-7-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-[7-ethyl-6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
salt triperoxonane acid 1-(3-tert-butyl-4-methoxy-5-morpholine-4-ylphenyl)-2-(6-ethoxy-8-ethyl-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)ethanone;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-[8-ethyl-6-(1-ethylpropoxy)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-8-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
salt triperoxonane acid 2-[6-(1-ethylpropoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]-1-[3-(2-hydroxyethoxy)-5-(pentafluoroethyl)phenyl]ethanone;
2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-(2-hydroxyethoxy)-5-(pentafluoroethyl)phenyl]economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-{6-ethoxy-7,8-dimethyl-3-[(E)-methylimino]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-{6-ethoxy-8-methyl-3-[(E)-methylimino]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-7-ethyl-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-7-ethyl-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-[6-ethoxy-8-(1-hydroxy-1-methylethyl)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-8-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-8-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(4-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(4-hydroxyethoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-{3-[(E)-cyclopropylamino]-6-ethoxy-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-7-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(4-hydroxyethoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
hydrochloride ethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-oxoethyl}-3-imino-8-methyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride dimethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-oxoethyl}-3-imino-8-methyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride methylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-oxoethyl}-3-imino-8-methyl-2,3-dihydro-[1,2,4]t is Iesolo[4,3-b]pyridazin-6-carboxylic acid;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-diethylamino-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-diethylamino-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(8-cyclopropyl-6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(8-cyclopropyl-6-ethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-cyclopropylmethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-cyclopropylmethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
hydrochloride ethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-oxoethyl}-3-imino-7,8-dimethyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride methylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-oxoethyl}3-imino-7,8-dimethyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
1-[3-tert-butyl-5-(1-hydroxy-1-methylethyl)phenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-7,8-diethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-7,8-diethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(4-hydroxyethoxy)-4-methoxyphenyl]-2-(6-cyclopropylmethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-cyclopropylmethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-cyclopropylmethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-(6-cyclopropylmethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-cyclopropylmethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-cyclopropylmethoxy-3-imino-8,9-dihydro-7H-cyclopent[d][1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)phenyl]-2-(6-cyclopropylmethoxy-3-imino--methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
hydrochloride methylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-3-[(E)-ethylimino]-7,8-dimethyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride ethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-7,8-dimethyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride methylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-7,8-dimethyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
1-[3-tert-butyl-5-(4-hydroxyethoxy)phenyl]-2-(6-cyclopropylmethoxy-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-8-ethyl-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-{6-ethoxy-7,8-dimethyl-3-[(S)-2,2,2-triptoreline]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-{6-ethoxy-7,8-dimethyl-3-[(S)-2,2,2-triptoreline]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-{6-ethoxy-7,8-dimethyl-3-[(S)-2,2,2-triptoreline]-[1,2,4]triazolo[4,3-b]pyridazin-2-yl}economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(3-imino-7,8-dimethyl-6-propoxy-[1,2,4]triazolo[4,-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(3-imino-6-isopropoxy-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(3-imino-7,8-dimethyl-6-propoxy-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-[3-imino-6-(2-methoxy-1-methoxymethylethoxy)-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-8-trifluoromethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(3-imino-7,8-dimethyl-6-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(3-imino-7,8-dimethyl-6-pyrrolidin-1-yl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-8-ethyl-3-imino-7-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-forproperty)phenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-floratone)phenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-[6-ethoxy-8-(taxidermal)-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-2-hydroxyethoxy)phenyl]-2-(6,8-diethoxy-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-4-methoxy-5-(2-methoxyethoxy)phenyl]-2-[3-imino-6-(2-methoxy-1-methoxymethylethoxy)-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl] economicrelated;
hydrochloride ethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-3-[(E)-ethylimino]-7,8-dimethyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride dimethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-7,8-dimethyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
1-[3-tert-butyl-4-methoxy-5-(3-methoxypropane)phenyl]-2-[3-imino-6-(2-methoxy-1-methoxymethylethoxy)-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicrelated;
1-[3-tert-butyl-5-(1-methoxy-1-methylethyl)phenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(3,3,3-cryptocracy)phenyl]-2-(6-ethoxy-3-imino-7,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
hydrochloride diethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-8-methyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride ethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-8-methyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride dimethylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methox the phenyl]-2-oxoethyl}-8-methyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-[6-(3-atiaxiety-3-ylethoxy)-3-imino-8-methyl-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]economicsamerica;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-[3-imino-8-methyl-6-(3-methyloxiran-3-ylethoxy)-[1,2,4]triazolo[4,3-b]pyridazin-2-economicsamerica
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-[3-imino-8-methyl-6-(oxetan-3-yloxy)-[1,2,4]triazolo[4,3-b]pyridazin-2-yl]ethanone;
hydrochloride methylamide 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)-4-methoxyphenyl]-2-oxoethyl}-8-methyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
hydrochloride ethylamide 2-{2-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-oxoethyl}-7,8-dimethyl-3-[(E)-methylimino]-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(3-imino-6,8-diisopropoxide-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(6-ethoxy-3-imino-8-isopropoxy-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
1-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-(3-imino-6,8-dimethoxy-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated;
hydrochloride of 2-{2-[3-tert-butyl-5-(2-hydroxyethoxy)phenyl]-2-oxoethyl}-3-imino-8-methyl-2,3-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-carboxylic acid;
2-(6-ethoxy-8-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)-1-[3-methoxy-5-(pendaftaran the Anil)phenyl]-economicrelated
or 1-[3-tert-butyl-5-(3-hydroxypropoxy)-4-methoxyphenyl]-2-(6-ethoxy-8-ethyl-3-imino-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)economicrelated]economicrelated.

4. The use of the compounds of formula (I) according to one or more of claims 1 to 3 in the way of prevention, secondary prevention and therapy of all diseases that occur with thrombosis, embolism or hypercoagulopathy.

5. The use according to claim 4, wherein the disease is myocardial infarction, angina, stroke, peripheral vascular disease, deep venous thrombosis, pulmonary embolism, embolic or thrombotic phenomena due to cardiac arrhythmias, restenosis after revascularization and angioplasty, stent implantation and the imposition of bypass, or reducing the risk of thrombosis after surgery as in the case of operations of knee and hip joints, or interference, leading to contact of blood with foreign surfaces as in the case of being treated with dialysis patients and patients with permanent catheters or disseminated intravascular coagulation, atherosclerosis.

6. The method of obtaining the compounds of formula (I) according to one or more of claims 1 to 3, characterized in that the compound of formula (II):

where R4-R8, Q2 and Q3 have specified the AK in the case of the formula (I) values, and W stands for chlorine, bromine, mesilato or tosylate group, enter into interaction with the compound of the formula (III):

where R1, R2, R3, and Q1 are specified as in the case of formula (I) values, with or without added base, in a solvent, to obtain the compounds of formula (I).



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formulas

and or pharmaceutically acceptable salts thereof, wherein the values R1-R13, Ra, Rb, Rc, Rd, Rf, Rq, n are presented in the patent claim possessing the properties of protein p53 activator.

EFFECT: compounds may be used in treating cancer and diseases caused by a fungal, bacterial or parasitic infection, eg malaria.

16 cl, 38 dwg, 12 tbl, 16 ex

Solid forms // 2496780

FIELD: chemistry; pharmaceutics.

SUBSTANCE: invention relates to crystalline forms of 4-[9-(tetrahydrofuran-3-yl)-8-(2,4,6-trifluorophenylamino)-9H-purin-2-ylamino]cyclohexan-1-ol of formula , which have kinase inhibiting properties and can be used to treat or prevent: (a) cancer; (b) an inflammatory condition or (c) an immunologic condition. The invention particularly relates to a crystalline form A, having an X-ray powder diffraction pattern with peaks at about 12.4, 16.0 and 18.5°2θ and further has peaks at about 17.7, 23.2 and 24.1°2θ; a hydrate crystalline form A, having an X-ray powder diffraction pattern with peaks at about 6.5, 13.0 and 23.0°2θ and further has peaks at about 13.4, 20.1 and 23.8°2θ; a crystalline form of a hydrochloride salt A, having an X-ray powder diffraction pattern with peaks at about 17.3, 18.7 and 22.4°2θ, and contains about two mole equivalents of chloride ions.

EFFECT: invention relates to methods of producing a crystalline form A, a pharmaceutical composition containing said crystalline forms and a treatment method.

15 cl, 16 dwg, 9 ex

FIELD: medicine.

SUBSTANCE: present invention describes compounds of formula I: wherein: X1 and X2 independently represent CH or N; R1 represents fluorine or hydrogen; R2 represents hydrogen, halogen; Ar represents phenyl substituted by 1-3 groups optionally substituted in each specific case in a group consisting of hydrogen, halogen, cyano group; R3 is independently specified in each specific case in a group consisting of: (i) CH2OH; (ii) CH2O-C(=O)(CH2)nCO2R4, wherein n has a value of 2 to 5; (iii) CH2O-C(=O)CH2OCH2CO2R4; (iv) CH2OCOR5; (v) CH2OC(=O)CHR6NH2; (vi) C(=O)R5, and (vii) CH2OP(=O)(OH)2; R4 represents hydrogen or C1-10 alkyl; R5 represents hydrogen or C1-10 alkyl, C1-3 dialkylamino-C1-10 alkyl, C1-6 alkoxy or pyridinyl, R6 represents C1-6 alkyl or a side chain of a natural amino acid; or a pharmaceutically acceptable salt thereof. Besides, the invention describes a pharmaceutical composition having HTVRT inhibitory activity and containing a compound according to cl.1.

EFFECT: there are prepared and described new compounds inhibiting HIV-1 reverse transcriptase and effective for preventing and treating HIV-1 infections and treating AIDS or ARC.

13 ex, 3 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new triazolium salts of general formula (I) stereo- and tautomer forms and physiologically acceptable salts thereof, wherein X- C-R1 or N, R1-hydrogen, C1-6alkyl or halogen; A- is an anion of a pharmacologically acceptable organic or inorganic acid; Q1 is hydrogn, -C1-6alkyl optionally substituted, -C3-6cycloalkyl, -C(O)-O-R11 or - C(O)-R11; R11 -C1-6alkyl; Q2 and Q3 are hydrogen; R2- R9 independently mean hydrogen, -C1-6alkyl optionally substituted, -O-(C1-8)alkyl optionally substituted, etc., and using the above compounds as a drug preparation.

EFFECT: compounds possess antithrombotic activity, particularly, they inhibit the protease-activated receptor 1 (PAR1), and may be used in treating the diseases such as myocardial infarction, angina, stroke, and others.

4 cl, 2 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: described is a sodium salt of 2-methyl-6-fluoro-1,2,4-triazolo[5,1-c]-1,2,4-triazin-7(4H)-one , having antiviral activity with respect to influenza virus A(H1N1).

EFFECT: improved properties of the compound.

1 cl, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention describes pyrrolo[2,3-d]pyrimidine derivatives of formula (I) or a pharmaceutically acceptable salt thereof, where R1 is C1-4 alkyl, optionally substituted with a hydroxy group, as well as a crystalline form A of a salt of N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl} methane sulphonamide with maleic acid. Disclosed also is a method of producing a salt of N-methyl-1-{trans-4-[methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl} methane sulphonamide with maleic acid.

EFFECT: improved properties of the composition, having inhibiting activity on Janus kinase and a method of treating allergic reactions, allergic dermatitis, atopic dermatitis, eczema or itching in mammals.

17 cl, 7 ex, 4 tbl, 3 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to novel pyrimidine derivatives of general formula (I), or pharmaceutically acceptable salts thereof, where X1 denotes N, N-R3, C-R3 or O; X2 denotes N, CH or C-CH3; X3 denotes N or C, where X1, X2 and X3 all do not simultaneously denote N; X4, X5 each independently denotes C or N; X6 denotes N or C-R1 ; where at least two and not more than four of X1, X2, X3, X4, X5 and X6 denotes N; and where the bonds between X1 and X2, X2 and X3, X3 and X4, X4 and X5, X5 and X1, as well as X5 and X6 can each independently be single or double, or , can form an aromatic ring, under the condition that a chemically stable structure is formed; R denotes -(cyclohexyl)R2; R1 denotes a halide, nitro group, -CN, -CH2CN, -OH, -NH2, -COOH or -Y1R4; Y1 denotes -O-, -SO2, -NHSO2-, -C(O)O- or a bond; R4 denotes (C1-C6)alkyl, phenyl or benzyl, each of which is substituted with 0-3 times with a hydroxy group or a halogen; n equals 0, 1 or 2; R3 denotes H or (C1-C6)alkyl; R2 denotes H, -OH, =O or -Y2-Y3-Y4-R5, where Y2 denotes -C(O)-, -C(O)NRa-, -NH- or a bond; Y3 denotes (C1-C6)alkylene or a bond; Y4 denotes -NRa-, -S-, -SO2-, -NRaC(O)-, -NHSO2- or a bond; R5 denotes (C1-C6)alkyl, (C3-C10)cycloalkyl, a 5-6-member heterocyclyl containing 1-2 heteroatoms selected from N and O, where R5 is optionally substituted with -OH or -NHRa; where each Ra independently denotes hydrogen or (C1-C6)alkyl; Z denotes hydrogen. The invention also relates to a pharmaceutical composition based on a compound of formula (I).

EFFECT: obtaining novel pyrimidine derivatives which are useful for therapeutic or preventive treatment of a c-Jun N-terminal kinase-mediated disorder.

14 cl, 3 tbl, 26 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to ocrahydropyrrolo[3,4-b]pyrrole derivatives of formula I: or their pharmaceutically acceptable salts, where values R1, R2a, R2b, R2c, R2d, R2e, R2f, R3a , R3b, R3c, R3d, Cy1, L2, Cy2 are given in item 1 of the formula. Method of their obtaining is described.

EFFECT: compounds can be used for treatment of organism therapeutically sensitive to binding of histamine-3 receptor.

47 cl, 22 dwg, 6 tbl, 87 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention discloses crystalline form of S-zopicone with spectrum of powder X-ray diffraction with application of Cu-Ka radiation, with characteristic peaks, expressed under conditions 20 approximately at 11.08°, approximately 12.38°, approximately 15.86°, approximately 17.88°, approximately 19.98°C and approximately 20.58°, DSC-thermogram, on which peak is observed approximately at 207.7°C, and infrared spectrum of absorption (IR) with characteristic peaks approximately at 3078 cm-1, approximately 2942-2838 cm-1, approximately 2790 cm-1, approximately 1716 cm-1, approximately 1463 cm-1, approximately 1372 cm-1 and approximately 757 cm-1.

EFFECT: claimed are: method of preparation of crystalline form of eszopiclone, pharmaceutical preparation and its application in manufacturing medication for treatment of sleep disorder.

8 cl, 8 dwg, 10 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula 1:

or pharmaceutically acceptable salts thereof, where values of Cy1; Cy2; L1; L2, R; R1; Rx and Ry and R2 are given in claim 1.

EFFECT: compounds are suitable for use as Raf protein kinase inhibitors.

36 cl, 6 tbl

FIELD: medicine.

SUBSTANCE: present invention refers to medicine, particularly to pharmacology, and describes a method for correction of disturbed functional activity of platelets, consisting in using Melaxen as a corrector for the disaggregation and hyperaggregation state of the platelets to be orally administered into white non-linear mature rats in a dose of 1 mg/kg once a day within the 7-day therapeutic course.

EFFECT: invention aims at extending the range of preparations having an ability to control the aggregation properties of platelets depending on the nature of the haemostatic disorders.

4 tbl, 4 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to anticoagulant compounds of formula (I) : and pharmaceutically acceptable salts thereof, wherein R represents C1-C8 alkyl substituted by at least one halogen specified in chlorine or fluorine.

EFFECT: invention refers to pharmaceutical compositions containing the compounds and salts thereof, as well as to using the compounds and salts thereof for treating bleeding disorders, to a method of treating, inhibiting epoxyredutase, vitamin K and coagulation factor synthesis.

31 cl, 3 tbl, 11 ex, 10 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described new triazolium salts of general formula (I) stereo- and tautomer forms and physiologically acceptable salts thereof, wherein X- C-R1 or N, R1-hydrogen, C1-6alkyl or halogen; A- is an anion of a pharmacologically acceptable organic or inorganic acid; Q1 is hydrogn, -C1-6alkyl optionally substituted, -C3-6cycloalkyl, -C(O)-O-R11 or - C(O)-R11; R11 -C1-6alkyl; Q2 and Q3 are hydrogen; R2- R9 independently mean hydrogen, -C1-6alkyl optionally substituted, -O-(C1-8)alkyl optionally substituted, etc., and using the above compounds as a drug preparation.

EFFECT: compounds possess antithrombotic activity, particularly, they inhibit the protease-activated receptor 1 (PAR1), and may be used in treating the diseases such as myocardial infarction, angina, stroke, and others.

4 cl, 2 tbl, 86 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a solid oral pharmaceutical formulation containing a hydrolised form of 5-chloro-M-({(5S)-2-oxo-3-[4-(3-oxo-4-morpholinyl)phenyl]-1,3-oxazolidin-5-yl}methyl)-2-thiophenecarboxamide in the amount of 1 to 60%. The formulation contains sodium lauryl sulphate as a wetting agent and hydroxypropylmethyl cellulose as a hydrophilic binding agent. The pharmaceutical formulation is presented in the form of a tablet.

EFFECT: formulation according to the invention provides higher biological availability of the active ingredient.

17 cl, 2 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a biologically active substance possessing the antiaggregant properties. The technical effect: what is produced is a drug preparation of a new compound of (2E)-3-[1-(2-hydroxy-3-piperidin-1-ylpropyl)-1 H-indol-3-yl]-1-(2-thienyl)prop-2-en-1-one hydrochloride of formula I possessing antiaggregant action:

.

EFFECT: substance may be used in medicine for producing a drug preparation for preventing the conditions associated with a high thrombogenic potential of blood.

1 cl, 2 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, namely to therapeutic agents used for treating ischemic cardiac disorders, and describes a combined medicine as a thrombocyte aggregation inhibitor containing an agent presented by a combination of clopidogrel or a pharmaceutically acceptable salt thereof, acetyl salicylic acid and magnesium hydroxide and additives.

EFFECT: invention provides enlarging the list of medicines and preparing the new combination of the agents possessing activity on platelet aggregation and the property to protect the gastric mucosa, as well as enhancing the clinical effectiveness of the medicine and prolonging its action.

13 cl, 3 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: invention describes crystals of 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine (prasugrel) hydrobromate, comprisions of crystals and pharmaceutical compositions containing them for preventing and treating the diseases associated with thrombus or embolism in an animal.

EFFECT: there are prepared new crystals of prasugrel hydrobromate which possess improved stability and solubility, and can find application in medicine.

13 cl, 7 dwg, 3 tbl, 11 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel 5-halogen-substituted oxindole derivatives of formula I: , where: R1 denotes hydrogen, methoxy or ethoxy group; R2 denotes hydrogen or a methoxy group; R3 denotes hydrogen, methyl, ethyl, n-propyl or isopropyl; R4 denotes an ethoxy or isopropoxy group; R5 denotes H or methyl; R6 denotes Cl or F; X1 denotes O, NH or CH2; X2 and X3 denotes N or CH under the condition that X2 and X3 do not denote N at the same time; as well as pharmaceutically acceptable salts thereof. The invention also relates to pharmaceutical compositions for treating and/or preventing vasopressin-dependent diseases, which contain derivatives of formula I, and use thereof in treating vasopressin-dependent diseases.

EFFECT: high efficiency of using said compounds.

25 cl, 8 ex, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely cardiology and concerns treating the patients with ST segment elevation acute myocardial infarction. That is ensured by the two-bolus intravenous administration of the thrombolytic preparation Fortelysine in a dose of 10 mg, and 30 minutes later in a dose of 5 mg.

EFFECT: presented mode of administration of Fortelysine provides the effective recovery of the antegrade coronary blood flow in the infarction-involved coronary artery in the patients with ST segment elevation acute myocardial infarction.

1 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine, particularly to paediatrics, X-ray surgery, paediatric surgery, and concerns the hemostatic disorder correction in the children with hepatic hemangiomas. For this purpose, three days before the endovascular embolisation of the hepatic hemangioma, Protromplex 600 - a preparation of plasma factors II, VII, IX, X is administered intravenously in a dose of 20 IU/kg at max. 2 ml/min; on the first postoperative day, Protromplex is administered in the same dose, and further Fraxiparine is administered subcutaneously in a dose of 158 IU/kg of body weight for 3 days.

EFFECT: presented dose schedule of the preparations provides the effective and safe correction of hemostatic disorders in the children with hepatic hemangiomas due to normalising the internal and external mechanisms of blood coagulation and fibrinolysis.

1 ex

FIELD: medicine.

SUBSTANCE: present invention describes compounds of formula I: wherein: X1 and X2 independently represent CH or N; R1 represents fluorine or hydrogen; R2 represents hydrogen, halogen; Ar represents phenyl substituted by 1-3 groups optionally substituted in each specific case in a group consisting of hydrogen, halogen, cyano group; R3 is independently specified in each specific case in a group consisting of: (i) CH2OH; (ii) CH2O-C(=O)(CH2)nCO2R4, wherein n has a value of 2 to 5; (iii) CH2O-C(=O)CH2OCH2CO2R4; (iv) CH2OCOR5; (v) CH2OC(=O)CHR6NH2; (vi) C(=O)R5, and (vii) CH2OP(=O)(OH)2; R4 represents hydrogen or C1-10 alkyl; R5 represents hydrogen or C1-10 alkyl, C1-3 dialkylamino-C1-10 alkyl, C1-6 alkoxy or pyridinyl, R6 represents C1-6 alkyl or a side chain of a natural amino acid; or a pharmaceutically acceptable salt thereof. Besides, the invention describes a pharmaceutical composition having HTVRT inhibitory activity and containing a compound according to cl.1.

EFFECT: there are prepared and described new compounds inhibiting HIV-1 reverse transcriptase and effective for preventing and treating HIV-1 infections and treating AIDS or ARC.

13 ex, 3 dwg

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