Isoquinolin-3-Ylurea Derivatives

A compound of formula I:

• wherein
• R1 represents (C1-C3)alkyl, (C2-C3)haloalkyl or cyclopropyl;
• R4 represents H;
• R3 represents H, R5 represents H and R2 represents phenyl or 4-carboxyphenyl;
• or
• R2 represents H, R5 represents H and R3 represents benzoylamino;
• or
• R2 represents H, R3 represents H and R5 represents —NH—CO—R6, —CH2—O—R7, —NH—R8, —CH2—NH—R9, —CH2—R10, (pyridin-3-ylmethyl)amino, pyridin-3-yloxy or 4-carboxyphenyl;
• or
• R3 represents H, R5 represents methyl and R2 represents halogen, (C1-C3)alkylamino, (C1-C3)alkylaminomethyl, 2-(aminocarbonyl)-ethyl, pyrimidin-4-yl, pyridazin-3-yl, pyridazin-4-yl, 1H-imidazol-4-yl, 1-methyl-1H-imidazol-4-yl, 1H-pyrazol-4-yl, 1-methyl-1H-pyrazol-4-yl, imidazo[1,2-a]pyridin-6-yl, 4-methyl-thiophen-3-yl, thiazol-4-yl, isoquinolin-5-yl or 1H-indol-4-yl or a group having the formula (A1), (A2) or (A3) shown hereafter
• wherein
• each of A13 and A14 represents H and A12 represents H or OH, or
• each of A12 and A14 represents H and A13 represents OH, acetylamino, aminomethyl, sulfamoyl or hydroxymethyl, or
• each of A12 and A13 represents H and A14 represents OH, methylaminocarbonyl, dimethylaminocarbonyl, methoxycarbonylamino, sulfamoyl or hydroxymethyl;
• each of A25 and A26 represents H and A22 represents H or halogen, or
• each of A22 and A26 represents H and A25 represents methyl or halogen, or
• each of A22 and A25 represents H and A26 represents hydroxymethyl;
• each of A33 and A36 represents H and A32 represents H, halogen, amino, methyl or methoxy, or
• A33 represents H and each of A32 and A36 represents methyl;
• or
• R2 represents H, R5 represents methyl and R3 represents amino, vinyl, (C1-C4)alkylamino, cyclopropylmethylamino, (2-(benzyloxy)ethyl)amino, methoxymethylcarbonylamino, (thiazol-5-yl)carbonylamino, pyridin-3-ylcarbonylamino, pyridin-4-ylcarbonylamino, naphthalen-2-yl, furan-2-yl, furan-3-yl, 1H-pyrazol-4-yl, thiophen-3-yl, 4-methyl-thiophen-3-yl, quinolin-3-yl, isoquinolin-4-yl, isoquinolin-5-yl, imidazo[1,2-a]pyridin-6-yl, 1H-indol-4-yl or a group having the formula (B1), (B2), (B3), (B4), (B5), (B6), (B7), (B8), (B9), (B10), (B11) or (B12) shown hereafter
• wherein
• each of B13 and B14 represents H and B12 represents OH, methyl, acetylamino, (C1-C2)alkoxycarbonyl or dimethylaminocarbonyl, or
• each of B12 and B14 represents H and B13 represents OH, halogen, acetyl, acetylamino, acetylammomethyl, aminocarbonyl, sulfamoyl, (C1-C2)alkoxy, (C1-C2)alkoxycarbonyl, cyano, amino-(C1-C2)alkyl or hydroxy-(C1-C2)alkyl, or
• each of B12 and B13 represents H and B14 represents acetyl, acetylamino, acetylammomethyl, aminocarbonyl, dimethylaminocarbonyl, sulfamoyl, (C1-C2)alkylsulfonyl, cyanomethyl or hydroxymethyl;
• X and X′ each represent —O— or one of X and X′ represents —O— and the other represents —CH2—;
• each of B35 and B36 represents H and B32 represents H or halogen, or
• each of B32 and B36 represents H and B35 represents halogen, methyl, methylsulfanyl, methanesulfonyl or methoxycarbonyl, or
• each of B32 and B35 represents H and B36 represents halogen, methoxy or hydroxymethyl;
• B43 represents H or halogen;
• B54 represents H or (C1-C3)alkyl;
• B64 represents H and B63 represents H, methoxycarbonyl or dimethylamino, or
• B63 represents H and B64 represents methoxy, methoxycarbonyl, dimethylamino or methane sulfonyl;
• B74 represents H and B73 represents H, methoxy, methoxycarbonyl, carboxy, 2-hydroxyethoxy, 1H-1,2,4-triazol-1-yl or 1H-1,2,4-triazol-1-ylmethyl, or
• B represents H and B represents carboxy, acetylamino, ((amino carbonyl)methyl)oxy, N-methylsulfamoyl or 3-methyl-1H-1,2,4-triazol-1-yl;
• B91 represents H or methyl;
• B111 represents H or morpholino;
• or
• R2 represents H, R5 represents pyridin-3-ylamino and R3 represents propylamino, 3-acetylamino-phenyl, benzylamino, 5-methylpyridin-3-yl or 3-(N,N-dimethylamino)phenylcarbonylamino;
• or
• R2 represents fluorine, R3 represents H and R5 represents bromine, benzyl, benzoylamino, 4-carboxyphenyl, benzylamino, pyridin-3-yl or (pyridin-3-ylmethyl)amino;
• or
• R2 represents bromine, R3 represents H and R5 represents methoxy;
• or
• R2 represents fluorine, R5 represents methyl and R3 represents quinolin-3-yl, benzylamino, a phenyl group optionally substituted once by acetylamino or sulfamoyl, pyridin-2-yl, or a pyridin-3-yl group optionally substituted once by methyl;
• or
• R2 represents fluorine, R3 represents pyridin-3-yl and R5 represents pyridin-3-yl or 4-carboxyphenyl;
• or
• R2 represents fluorine, R3 represents benzylamino and R5 represents chlorine or 2-methoxy-pyrimidin-5-yl;
• or
• R2 represents fluorine, R3 represents quinolin-3-yl and R5 represents quinolin-3-yl;
• or
• R2 represents fluorine, R3 represents 3-(acetylamino)phenyl and R5 represents pyridin-3-yl, pyridin-3-ylamino or 2-methoxypyrimidin-5-yl;
• or
• R2 represents fluorine, R3 represents 4-sulfamoyl-phenyl and R5 represents chlorine;
• or
• R2 represents fluorine, R5 represents pyridin-3-ylamino and R3 represents benzylamino or 5-methylpyridin-3-yl;
• or
• R3 represents H, R2 represents (C1-C3)alkylaminomethyl, N,N-dimethylaminomethyl, pyridin-3-yl, pyridin-4-yl, 2-methylpyridin-4-yl, 2-methoxypyridin-4-yl, 2-aminopyridin-4-yl, 2,6-dimethylpyridin-4-yl, pyrimidin-4-yl, 1H-imidazol-4-yl, 1H-pyrazol-4-yl, thiazol-4-yl, pyridin-3-ylamino, 3-(aminomethyl)phenyl, 4-hydroxyphenyl, 4-(hydroxymethyl)phenyl, 4-sulfamoyl-phenyl, morpholino, morpholinomethyl, 4-methylpiperazin-1-yl or 4-methyl-piperazin-1-ylmethyl and R5 represents chlorine, vinyl, methoxy, (3-carboxyphenyl)amino, (3-(methoxycarbonyl)phenyl)amino, (3-(dimethylcarbamoyl)phenyl)amino, (3-(methylcarbamoyl)phenyl)amino, pyridin-4-yl, (6-methyl-pyridin-2-yl)amino, (6-methoxy-pyridin-2-yl)amino, pyridin-3-ylamino, (6-methyl-pyridin-3-yl)amino or pyridin-3-yloxy;
• R6 represents phenyl, 1H-pyrrol-2-yl or 1H-1,2,3-triazol-5-yl;
• R7 represents pyridin-2-yl, 5-methyl-pyridin-2-yl, 2-methyl-pyridin-3-yl, 6-methyl-pyridin-3-yl, pyridin-4-yl, 3-methoxycarbonyl-pyridin-4-yl, 2-(methoxycarbonyl)phenyl, 3-hydroxy-phenyl or 3-amino-phenyl;
• R8 represents pyridin-2-yl, 6-methoxy-pyridin-2-yl, 5-methoxy-pyridin-2-yl, 4-methoxy-pyridin-2-yl, 3-methyl-pyridin-2-yl, 4-methyl-pyridin-2-yl, 5-methyl-pyridin-2-yl, 6-methyl-pyridin-2-yl, 5-aminocarbonyl-pyridin-2-yl, 4-fluoro-pyridin-2-yl, 5-methoxycarbonyl-pyridin-2-yl, 6-methoxycarbonyl-pyridin-2-yl, pyridin-3-yl, 5-fluoro-pyridin-3-yl, 2-methoxypyridin-3-yl, 5-methoxy-pyridin-3-yl, 6-methoxy-pyridin-3-yl, 6-acetylamino-pyridin-3-yl, 6-methyl-pyridin-3-yl, pyridin-4-yl, 2-methoxy-pyridin-4-yl, 3-fluoro-pyridin-4-yl, pyrazin-2-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, phenyl, 3-hydroxyphenyl, 3-methoxyphenyl, 3-carboxyphenyl, 3-carbamoylphenyl, 3-acetylamino-phenyl, 3-sulfamoylphenyl, 3-methoxycarbonyl-phenyl, 4-methyl-3-methoxycarbonyl-phenyl, 4-methyl-3-carboxyphenyl, 3-(carboxymethyl)phenyl, 3-(methylcarbamoyl)phenyl, 3-(dimethylcarbamoyl)phenyl, 3-(benzylcarbamoyl)phenyl, 3-(2-amino-2-oxoethyl)phenyl, 3-(2-(dimethylamino)-2-oxoethyl)phenyl, 3-(2-(benzylamino)-2-oxoethyl)phenyl, 4-methoxycarbonyl-phenyl, 3-methyl-4-methoxycarbonyl-phenyl, 4-carboxyphenyl, 3-methyl-4-carboxyphenyl, 3-carbamoyl-4-methoxyphenyl, 4-methoxy-3-(methylcarbamoyl)phenyl, 3-(dimethylcarbamoyl)-4-methoxyphenyl, 4-hydroxyphenyl, 4-(carboxymethyl)phenyl, 4-cyanophenyl, 4-acetylamino-phenyl, 4-carbamoylphenyl, 4-(methylcarbamoyl)phenyl, 4-(dimethylcarbamoyl)phenyl, 4-(2-amino-2-oxoethyl)phenyl, 4-(2-(dimethylamino)-2-oxoethyl)phenyl, 4-(2-(methylamino)-2-oxoethyl)phenyl, 4-(2-(benzylamino)-2-oxoethyl)phenyl, 5-methyl-1,3,4-oxadiazol-2-yl or imidazo[1,2-a]pyridin-7-yl;
• R9 represents pyridin-2-yl, pyridin-3-yl, 6-methoxypyridin-3-yl, pyrimidin-2-yl, 1,3-dimethyl-1H-pyrazol-5-yl, 1-methyl-1H-pyrazol-5-yl, 5-methylisoxazol-3-yl or 3-methylisothiazol-5-yl;
• R10 represents 1H-imidazol-1-yl, 4-(hydroxymethyl)-1H-imidazol-1-yl, 5-(hydroxymethyl)-1H-imidazol-1-yl, 2-carboxy-1H-imidazol-1-yl, 2,4-dimethyl-1H-imidazol-1-yl, 2,5-dimethyl-1H-imidazol-1-yl, 2-methyl-1H-imidazol-1-yl, 1H-1,2,3-triazol-1-yl, 1H-pyrazol-1-yl, 4-methyl-1H-pyrazol-1-yl or 4-(hydroxymethyl)-1H-pyrazol-1-yl;
• or a salt thereof.