Pyrazole derivative

A pharmaceutical composition which comprises a pharmaceutically effective amount of a pyrazole compound represented by the following general formula (I′) or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier

• wherein each symbol has the following meaning,
• D:
• 1H-pyrazol-1-yl, which may have 1 to 2 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, halogeno-lower alkyl-, -cycloalkyl, —O-Alk, —COO-Alk and -Hal,
• n:
• 0,
• B:
• 1,4-phenylene,
• X:
• —NH—CO—, and
• A:
• aryl which may have one or more substituents of group F;
• mono- or di-cyclic fused heteroaryl selected from the group consisting of thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyt, isothiazolyl, oxazolyl, isoxazolyl, tetrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, isoquinolyl, quinolyl, quinoxanyl, phthalazinyl, imidazo[1,2-a]pyridyl, quinazolinyl and cinnolinyl which may have one or more substituents of group F;
• cycloalkyl;
• or Alk, wherein the F group is:
• -Alk, -lower alkenyl, -lower alkynyl, -Hal, —NH2, —NH(Alk), —N(Alk)2, —NO2, —CN, —OH, —O-Alk, —O—CO-Alk, —SH, —S-Alk, —COO-Alk, —CO-Alk, —CONH2, —CONH(Alk), —CON(Alk)2, —SO-Alk, —SO2-Alk, and —SO2NH2,
• with the proviso that
• (1) when D is 3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl, n is 0, B is 1,4-phenylene and X is NHCO, A is a group other than 4-methyl-1,2,3-thiadiazol-5-yl,
• (2) when D is 1H-pyrazol-1-yl, n is 0, B is 1,4-phenylene and X is NHCO, A is a group other than methyl,
• (3) when D is 3,5-dimethyl-1H-pyrazol-1-yl, n is 0, B is 1,4-phenylene and X is NHCO, A is a group other than methyl, and
• (4) when D is 3-methyl-4-bromo-1H-pyrazol-1-yl, n is 0, B is 1,4-phenylene and X is NHCO, A is a group other than methyl.

A method for treating bronchial asthma, which comprises administering a pharmaceutical composition comprising a pyrazole compound represented by the following general formula (I′)

• wherein each symbol has the following meaning,
• D:
• 1H-pyrazol-1-yl, which may have 1 to 2 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, halogeno-lower alkyl-, -cycloalkyl, —O-Alk, —COO-Alk and -Hal,
• n:
• 0,
• B:
• 1,4-phenylene,
• X:
• —NH—CO—, and
• A:
• aryl which may have one or more substituents of group F;
• mono- or di-cyclic fused heteroaryl selected from the group consisting of thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, tetrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, isoquinolyl, quinolyl, quinoxanyl, phthalazinyl, imidazo[1,2-a]pyridyl, quinazolinyl and cinnolinyl which may have one or more substituents of group F;
• cycloalkyl;
• or Alk, wherein the F group is:
• -Alk, -lower alkenyl, -lower alkynyl, -Hal, —NH2, —NH(Alk), —N(Alk)2, —NO2, —CN, —OH, —O-Alk, —O—CO-Alk, —SH, —S-Alk, —COO-Alk, —CO-Alk, —CONH2, —CONH(Alk), —CON(Alk)2, —SO-Alk, —SO2-Alk, and —SO2NH2,
• with the proviso that
• when D is 3,5-bis(trifluoromethyl-1H-pyrazol-1-yl, n is 0, B is 1,4-phenylene and X is NHCO, A is a group other than 4-methyl-1,2,3-thiadiazol-5-yl,
• or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, in an effective amount for treating said disease in a patient suffering from or susceptible to said disease.

A method for treating rheumatoid arthritis, which comprises administering a pharmaceutical composition comprising a pyrazole compound represented by the following general formula (I′)

• wherein each symbol has the following meaning,
• D:
• 1H-pyrazol-1-yl, which may have 1 to 2 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, halogeno-lower alkyl-, -cycloalcyl, —O-Alk, —COO-Alk and -Hal,
• n:
• 0,
• B:
• 1,4-phenylene,
• X:
• —NH—CO—, and
• A:
• aryl which may have one or more substituents of group F;
• mono- or di-cyclic fused heteroaryl selected from the group consisting of thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, tetrazolyl, triazolyl, thiadiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, isoquinolyl, quinolyl, quinoxanyl, phihalazinyl, imidazo[1,2-a]pyridyl, quinazolinyl and cinnolinyl which may have one or more substituents of group F;
• cycloalkyl;
• or -Alk, wherein the F group is:
• -Alk, -lower alkenyl, -lower alkynyl, -Hal, —NH2, —NH(Alk), —N(Alk)2, —NO2, —CN, —OH, —O-Alk, —O—CO-Alk, —SH, —S-Alk, —COO-Alk, —CO-Alk, —CONH2, —CONH(Alk), —CON(Alk)2, —SO-Alk, —SO2-Alk, and —SO2NH2,
• with the proviso that
• when D is 3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl, n is 0, B is 1,4-phenylene and X is NHCO, A is a group other than 4-methyl-1,2,3-thiadiazol-5-yl,
• or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, in an effective amount for treating said disease in a patient suffering from or susceptible to said disease.