Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same

摘要

The present invention is for the anti-inflammatory compounds that have an inhibitory activity against protein tyrosine kinases and their pharmaceutical composition(s) containing the compound as the active ingredient. Since the compounds of the present invention can inhibit multiple protein kinases associated with inflammatory diseases and immune disorders, they are useful for their prevention or treatment.

主权项

1. A compound of the following chemical formula 1, or pharmaceutically acceptable salts thereof: wherein,
X1 is N or CH;R1 is —OH or —OCH3;Y is C6-10 aryl substituted with R2, or C5-10 heteroaryl substituted with R2 or N-methylpiperazinyl;R2 is —(CH2)n—R3, —(CH2)n—C(O)—R3, or —O(CH2)n—R3;R3 is —H, —CN, halogen, C1-3 alkyl, C1-3 alkoxy, phenyl, pyridinyl, amino, C1-3 alkyl amino, di C1-3 alkyl amino, hydroxyl C1-3 alkyl amino, carboxy C1-3 alkyl amino, C3-6 cycloalkyl C1-3 alkylamino, pyrolidinyl, hydroxyl pyrolidinyl, hydroxyl C1-3 alkylpyrolidinyl, carboxypyrolidinyl, piperidinyl, C1-3 alkylpiperidinyl, di C1-3 alkyl piperidinyl, piperazinyl, C1-3 alkylpiperazinyl, C1-4 alkoxycarbonylpiperazinyl, or morpholinyl; andn is an integer selected from 0 to 3, and wherein the compound of the chemical formula 1 is any one selected from the group consisting of— 3(6-(phenylthieno[3,2-d]pyrimidine-4-ylamino)phenol, 4-(4-(3-methoxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzonitrile, 4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzonitrile, 4-(4-(3-methoxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenol, 3-[6-(4-methoxyphenyl)-thieno[3,2-d]pyrimidine-4-nylamino]-phenol, N-(3-methoxyphenyl)-6-(4-(2-morpholinoethoxy)phenyl)thieno[3,2-d]pyrimidine-4-amine, 3-(6-(4-chlorophenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-(2-morpholinoethoxy)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, N-(3-methoxyphenyl)-6-(4-phenethoxyphenyl)thieno[3,2-d]pyrimidine-4-amine, N-(3-methoxyphenyl)-6-(4-(2-(pyridine-2-yl)ethoxy)phenyl)thieno[3,2-d]pyrimidine-4-amine, (6-furan-2-yl-thieno[3,2-d]pyrimidine-4-yl)-(3-methoxyphenol)-amine, (6-furan-3-yl-thieno[3,2-d]pyrimidine-4-yl)-(3-methoxyphenol)-amine, N-(3-methoxyphenyl)-6-(4-(2-(pyrolidine-1-yl)ethoxy)phenyl)thieno[3,2-d]pyrimidine-4-amine, N-(3-methoxyphenyl)-6-(thiophene-2-yl)thieno[3,2-d]pyrimidine-4-amine, (3-methoxyphenyl)-(6-thiophene-3-yl-thieno[3,2-d]pyrimidine-4-yl)-amine, N-(3-methoxyphenyl)-6-(4-(2-(piperazine-1-yl)ethoxy)phenyl)thieno[3,2-d]pyrimidine-4-amine, (3-methoxyphenyl)-(6-thiophene-2-yl-thieno[3,2-d]pyrimidine-4-yl)-amine, 3-(6-thiophene-3-yl-thieno[3,2-d]pyrimidine-4-ylamino)-phenol, 3-((6-(4-(morpholinomethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-(piperazine-1-ylmethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-(pyrolidine-1-ylmethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-(piperidine-ylmethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-((4-methylpiperazine-1-yl-methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-((diethylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-((cyclopropylmethylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-((isobutylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-((ethylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-(2-(pyrolidine-1-yl)ethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-(2-(piperidine-1-yl)ethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-((6-(4-(2-(4-methylpiperazine-1-yl)ethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-(2-morpholinoethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 2-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenyl)-1-(4-methylpiperazine-1-yl)ethanone, 2-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenyl)-1-(pyrolidine-1-yl)ethanone, N,N-diethyl-2-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenyl)acetamide, 3-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzoic acid, (4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenyl)(4-methylpiperazine-1-yl)methanone, (3-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenyl(pyrolidine-1-yl)methanone, N,N-diethyl-3-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzamide, (3-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)phenyl(4-methylpiperazine-1-yl)methanone, methyl 1-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzyl)pyrolidine-2-carboxylate, 3-(6-(4-((2-(hydroxymethyl)pyrolidine-1-yl)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-((4-methylpiperidine-1-yl)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-(((2R,6S)-2,6-dimethylpiperidine-1-yl)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-(piperidine-1-ylmethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-((4-methylpiperazine-1-yl)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-(pyrolidine-1-ylmethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-((diethylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-(piperazine-1-ylmethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-((ethylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-(morpholinomethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 1-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzyl)pyrolidine-2-carboxamide HCl salt, 1-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzyl)pyrolidine-2-carboxylic acid HCl salt, 3-(6-(4((2-hydroxyethylamino)methyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, methyl 2-(3-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzamido)propanoate, 1-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzyl)pyrolidine-3-ol HCl salt, 3-(6-(4-(ethoxymethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)-N-(1-hydroxyprophane-2-yl)benzamide, 2-(4-(4-(3-hydroxyphenylamino)thieno[3,2-d]pyrimidine-6-yl)benzamido)prophane acid, 3-(6-(3-(2-(pyrolidine-1-yl)ethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(3-(2-(piperazine-1-yl)ethyl)phenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(2-(4-(pyrolidine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(6-(4-morpholinophenyl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(2-(4-(morpholinomethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(4-((4-methylpiperazine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(6-(5-(pyrolidine-1-ylmethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-(pyrolidine-1-ylmethyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5((4-methylpiperazine-1-yl)methyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-(piperidine-1-ylmethyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-(morpholinomethyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-(piperazine-1-ylmethyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-((ethylamino)methyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-((4-methylpiperazine-1-yl)methyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-(piperidine-1-ylmethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-(piperazine-1-ylmethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(5-((ethylamino)methyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(2-(4-(piperidine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(4-(piperazine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(4-((ethylamino)methyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(4-methylpiperazine-1-yl)thiazolo[4,5-d]pyrimidine-7-ylamino)phenol, 3-(6-(4-(pyrolidine-1-ylmethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-((4-methylpiperazine-1-yl)methyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-(piperidine-1-ylmethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-(morpholinomethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol trifluoroacetic acid) 3-(6-(4-(piperazine-1-ylmethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol trifluoroacetic acid 3-(6-(4-((ethylaminomethyl)thiophene-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(2-(3-(pyrolidine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(3-((4-methylpiperazine-1-yl)methyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(3-(piperidine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(3-(morpholinomethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(3-(piperazine-1-ylmethyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(2-(3-((ethylamino)methyl)phenyl)thieno[3,2-b]pyridine-7-ylamino)phenol, 3-(6-(4-(pyrolidine-1-ylmethyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol, 3-(6-(4-((4-methylpiperazine-1-yl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol trifluoroacetic acid or 3-(6-(4-(piperidine-1-ylmethyl)furan-2-yl)thieno[3,2-d]pyrimidine-4-ylamino)phenol.