DIFLUOROMETHYLENE COMPOUND

摘要

The present invention relates to a compound having an URAT1 inhibitory activity, and to an URAT1 inhibitor, a blood uric acid level-reducing agent and a pharmaceutical composition containing the compound.;More specifically, the present invention relates to a compound represented by the formula (I):;;wherein
R1 is -Q1-A1 or the like; R2 is a hydrogen atom, a halogen atom, a lower alkyl group or the like; W1, W2, W3 and W4 are each independently a nitrogen atom or a methine group optionally having substituents, or the like; X and Y are each a single bond, an oxygen atom or the like; Z is a hydroxyl group or COOR3 or the like.

主权项

1. A compound represented by the formula (I) or a pharmaceutically acceptable salt or ester of the compound: the formula (I):wherein
R1 represents a lower alkyl group optionally substituted by a cycloalkyl group, a cycloalkyl group, a halo lower alkyl group, a hydroxy lower alkyl group, a lower alkoxy lower alkyl group, a lower alkoxy carbonyl group, a lower alkyl sulfonyl group or a group represented by the general formula: -Q1-A1; Q1 represents a single bond or a lower alkylene group (wherein the entirety of each of the 1 or 2 or more methylene group(s) that constitute(s) the lower alkylene group may be independently replaced with a carbonyl group, a sulfinyl group or a sulfonyl group, and/or the hydrogen(s) that constitute(s) the methylene group(s) may be substituted by lower alkyl group(s)); A1 represents an aryl group or a heteroaryl group optionally substituted by 1 to 3 substituent(s) selected from the following (wherein the adjacent optional two substituents on the aryl group or heteroaryl group may be together to form a lower alkylenedioxy group); R2 represents a hydrogen atom, a substituent selected from the following or a group represented by the general formula: -Q2-A2; Q2 represents a single bond, a lower alkylene group or lower alkenylene group (wherein the entirety of each of the 1 or 2 or more methylene group(s) that constitute(s) the lower alkylene group may be independently replaced with an oxygen atom, a nitrogen atom or a carbonyl group, and/or the hydrogen(s) that constitute(s) the methylene group(s) may be substituted by a halogen atom, a cyano group, a hydroxyl group or a lower alkyl group); A2 represents a cycloalkyl group, an aliphatic heterocycle group, an aryl group or a heteroaryl group optionally substituted by 1 to 3 substituent(s) selected from (wherein the adjacent optional two substituents on the aryl group or heteroaryl group may be together to form a lower alkylenedioxy group); W1, W2, W3 and W4 are each independently a nitrogen atom, or a methine group optionally having substituent(s) selected from the group consisting of a halogen atom, a hydroxyl group, a cyano group, a lower alkyl group, a cycloalkyl group, a halo lower alkyl group, a lower alkoxy group and a halo lower alkoxy group; provided that 0 to 4 of W1, W2, W3 and W4 is/are nitrogen atom(s); X and Y are each independently a single bond, a lower alkylene group, a lower alkenylene group or a lower alkynylene group (wherein the entirety of each of the 1 or 2 or more methylene group(s) that constitute(s) the lower alkylene group may be independently replaced with an oxygen atom, a sulfur atom, a sulfinyl group, a sulfonyl group, a carbonyl group or a group represented by the general formula: —N(RN)—, and/or the hydrogen(s) that constitute(s) the methylene group(s) may be substituted by a halogen atom, a cyano group, a hydroxyl group or a lower alkyl group; RN represents a hydrogen atom, a lower alkyl group, a halo lower alkyl group or a lower alkanoyl group; Z represents a hydroxyl group, COOR3, CONR4R5, SO3R3, SO3NR4R5, a 5-tetrazolyl group, a 5-oxo-1,2,4-oxadiazolyl group, a 2-oxo-1,3,4-oxadiazolyl group, a 5-imino-4,5-dihydro-1,3,4-oxadiazolyl group, a 2-thioxo-1,3,4-oxadiazolyl group or a 5-oxo-1,2,4-thiaziazolyl group; wherein R3, R4 and R5 each independently represents a hydrogen atom or a lower alkyl group; and and are defined as follows.:
a halogen atom, a hydroxyl group, a nitro group, a cyano group, a formyl group, an amino group, a carboxyl group, a lower alkyl group, a halo lower alkyl group, a cycloalkyl group, a lower alkoxy group, a halo lower alkoxy group, a hydroxy lower alkyl group, a lower alkoxy lower alkyl group, a lower alkoxy carbonyl group, a lower alkanoyl group, a lower alkylthio group, a lower alkyl sulfonyl group, a lower alkylamino group, a di-lower alkylamino group, a carbamoyl group, a mono-lower alkyl carbamoyl group, a di-lower alkyl carbamoyl group, a lower alkanoyl amino group, a lower alkyl sulfonylamino group, a lower alkoxy carbonylamino group, an aralkyl group, an aryloxy group, a heteroaryloxy group, a lower alkenyl group, and a cyano lower alkyl group:
a halogen atom, a hydroxyl group, a nitro group, a cyano group, a formyl group, an amino group, a carboxyl group, a lower alkyl group, a halo lower alkyl group, a cycloalkyl group, a lower alkoxy group, a halo lower alkoxy group, a hydroxy lower alkyl group, a lower alkoxy lower alkyl group, a lower alkoxy carbonyl group, a lower alkanoyl group, a lower alkylthio group, a lower alkyl sulfonyl group, a lower alkylamino group, a di-lower alkylamino group, a carbamoyl group, a mono-lower alkyl carbamoyl group, a di-lower alkyl carbamoyl group, a lower alkanoyl amino group, a lower alkyl sulfonylamino group, and a lower alkoxycarbonylamino group].