US 7,071,189 B2 · Heterocyclic compound and antitumor agent containing the same as active ingredient

Abstract

The present invention relates to heterocyclic compounds represented by the formula I or pharmaceutically acceptable salts thereof and antitumor agents containing the heterocyclic compounds as effective components: wherein X represents nitrogen atom or CH; R1 represents CHnF3-n (wherein n is 1 or 2), hydroxy C1–C6 alkyl, NHR6 [wherein R6 represents hydrogen atom or COR (wherein R represents hydrogen atom, C1–C6 alkyl or C1–C6 alkoxy)]; R2 represents morpholino (which may be substituted with one to four C1–C6 alkyl), thiomorpholino, piperidino, pyrrolidinyl (which may be substituted with hydroxy C1–C6 alkyl), oxazolidinyl (which may be substituted with one or two C1–C6 alkyl) or tetrahydro-1,4-thiazin-1-oxo-4-yl; R3 and R4 each represent hydrogen atom or C1–C6 alkyl; and R5 represents hydrogen atom, amino or hydroxyl.

Claims32

Dependent claims

A heterocyclic compound represented by the formula I or a pharmaceutically acceptable salt thereof:

wherein X represents nitrogen atom or CH;
R1 represents CHnF3-n (wherein n is 1 or 2), hydroxy C1–C6 alkyl, NHR6 (wherein R6 represents a hydrogen atom or COR (wherein R represents a hydrogen atom, C1–C6 alkyl or C1–C6 alkoxy));
R2 represents morpholino (which may be substituted with one to four C1–C6 alkyl), thiomorpholino, piperidino, pyrrolidinyl (which may be substituted with hydroxy C1–C6 alkyl), oxazolidinyl (which may be substituted with one or two C1–C6 alkyl) or tetrahydro-1,4-thiazin-1-oxo-4-yl;
R3 and R4 each represent hydrogen atom or C1–C6 alkyl;
and
R5 represents hydrogen atom, amino or hydroxyl.

3 more elements

A compound selected from the group consisting of:

2-(2-difluoromethylbenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholinopyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-thiomorpholinopyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholinopynmidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(2-methylmorpholino)-6-morpholinopyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-[2,2,5(R)-trimethylmorpholino]pyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-[2,2,5(S)-trimethylmorpholino]pyrimidine,
4-(cis-2,3-dimethylmorpholino)-2-(2-fluoromethylbenzimidazol-1-yl)-6-morpholinopyrimidine,
2-(2-aminobenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2-aminobenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-morpholinopyrimidine,
4-(cis-2,3-dimethylmorpholino)-2-(2-hydroxymethylbenzimidazol-1-yl)-6-morpholinopyrimidine,
4-(cis-2,3-dimethylmorpholino)-2-(2-hydroxymethylbenzimidazol-1-yl)-6-piperidinopyrimidine,
4-(cis-2,3-dimethylmorpholino)-2-(2-hydroxymethylbenzimidazol-1-yl)-6-(2-hydroxymethylpyrrolidin-1-yl)pyrimidine,
2-(6-amino-2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholinopyrimidine,
2-(6-amino-2-difluoromethylbenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2-difluoromethyl-5-hydroxybenzimidazol-1-yl)-4,6-dimorpholinopyrimidine,
2-(2-difluoromethyl-4-hydroxybenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2,4-diaminobenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2,4-diaminobenzimidazol-1-yl)-4,6-dimorpholinopyrimidine,
2-(2-amino-4-hydroxybenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-thiomorpholino-1,3,5-trazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(2-methylmorpholino)-6-morpholino-1,3,5-trazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(trans-2,5-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-[2,2,5(R)-trimethylmorpholino]-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-tetrahydro-1,4-thiazin-1-oxo-4-yl-1,3,5-triazine,
2-(2-acetylaminobenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-acetylaminobenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-morpholinopyrimidine,
2-(2-formylaminobenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-propionylaminobenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(trans-2,3-dimethylmorpholino)-4-(2-formylaminobenzimidazol-1-yl)-6-morpholino-1,3,5-triazine,
4-(trans-2,3-dimethylmorpholino)-2-(2-formylaminobenzimidazol-1-yl)-6-morpholinopyrimidine,
2-(cis-2,6-dimethylmorpholino)-4-(2-formylaminobenzimidazol-1-yl)-6-morpholino-1,3,5-triazine,
2-(2-methoxycarbonylaminobenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-aminobenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-aminobenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-morpholino-1,3,5-trazine,
2-(2-aminobenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-piperidino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-morpholino-6-piperidino-1,3,5-triazine,
2-(2-difluoromethylbenzimidazol-1-yl)-4-(trans-2,3-dimethylmorpholino)-6-(2-hydroxymethylpyrrolidin-1-yl)-1,3,5-triazine,
2-(6-amino-2-difluoromethylbenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(6-amino-2-difluoromethylbenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(4-amino-2-difluoromethylbenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-difluoromethyl-5-hydroxybenzimidazol-1-yl)-4-(cis-2,3-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethyl-6-hydroxybenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethyl-5-hydroxybenzimidazol-1-yl)-4-(2,2-dimethyloxazolidin-3-yl)-6-morpholino-1,3,5-triazine,
2-(2-difluoromethyl-4-hydroxybenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine,
2-(2-difluoromethyl-4-hydroxybenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2,4-diaminobenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholino-1,3,5-triazine,
2-(2,4-diaminobenzimidazol-1-yl)-4,6-dimorpholino-1,3,5-triazine, and
2-(2-amino-4-hydroxybenzimidazol-1-yl)-4-(2,2-dimethylmorpholino)-6-morpholino-1,3,5-triazine.

51 more elements

Dependencies are inferred from the claim text.

Heterocyclic compound and antitumor agent containing the same as active ingredient

Life of this patent

Heterocyclic compound and antitumor agent containing the same as active ingredient

Life of this patent

Abstract

Claims32