4,5-dihydro-1H-pyrazole derivatives having CB1-antagonistic activity

A compound of formula (III), or a tautomer, a stereoisomer, or a salt thereof:

• wherein R2 represents a hydroxy group,
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl, and
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or R1 represents naphthyl.

A compound of formula (V), or a tautomer, a stereoisomer, or a salt thereof:

• wherein
• Aa represents one of groups (i), (ii), or (v)
• wherein
• R4 represents hydrogen, C1-8 branched or unbranched alkyl or C3-8 cycloalkyl;
• and when R5 represents hydrogen, R4 optionally further represents acetamido, dimethylamino, 2,2,2-trifluoroethyl, phenyl or pyridyl,
• R5 represents hydrogen, C1-8 branched or unbranched alkyl or C3-8 cycloalkyl,
• R6 represents hydrogen or C1-3 unbranched alkyl,
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl,
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R1 represents naphthyl, and
• R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy.

A compound of formula (VII), or a tautomer, a stereoisomer, or a salt thereof:

• wherein
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl,
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R1 represents naphthyl,
• R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy,
• R3 represents benzyl, phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different, or R3 represents C1-8 branched or unbranched alkyl or C3-8 cycloalkyl, or R3 represents naphthyl, and
• Bb represents sulfonyl or carbonyl.

A compound of formula (IX), or a tautomer, a stereoisomer, or a salt thereof:

• wherein
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl,
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R1 represents naphthyl,
• R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy,
• R3 represents benzyl, phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different, or R3 represents C1-8 branched or unbranched alkyl or C3-8 cycloalkyl, or R3 represents naphthyl,
• and
• Bb represents sulfonyl or carbonyl.

A compound of formula (X), or a tautomer, a stereoisomer, or a salt thereof:

• wherein
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl,
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R1 represents naphthyl,
• R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy,
• R3 represents benzyl, phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different, or R3 represents C1-8 branched or unbranched alkyl or C3-8 cycloalkyl, or R3 represents naphthyl,
• Bb represents sulfonyl or carbonyl,
• and
• R8 represents a halogen atom.

A compound of formula (XII), or a tautomer, a stereoisomer, or a salt thereof:

• wherein
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl,
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R1 represents naphthyl,
• R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy,
• R3 represents benzyl, phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different, or R3 represents C1-8 branched or unbranched alkyl or C3-8 cycloalkyl, or R3 represents naphthyl,
• Bb represents sulfonyl or carbonyl,
• and
• R9 represents a C1-3 alkyl group.

A compound of formula (XVII), or a tautomer, a stereoisomer, or a salt thereof:

• wherein
• R represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R represents naphthyl,
• R1 represents phenyl, thienyl or pyridyl, each of which is unsubstituted or substituted with 1, 2 or 3 substituents Y, which are the same or different and are chosen from
• C1-3-alkyl, C1-3-alkoxy, hydroxy, halogen, trifluoromethyl, trifluoromethylthio, trifluoromethoxy, nitro, amino, monoalkyl (C1-2)-amino, dialkyl (C1-2)-amino, monoalkyl (C1-2)-amido, dialkyl (C1-2)-amido, (C1-3)-alkyl sulfonyl, dimethylsulfamido, C1-3-alkoxycarbonyl, carboxyl, trifluoromethylsulfonyl, cyano, carbamoyl, sulfamoyl and acetyl,
• or
• R1 represents naphthyl,
• R2 represents hydrogen, hydroxy, C1-3-alkoxy, acetyloxy or propionyloxy,
• Aa represents the group (v)
• wherein
• R6 represents hydrogen or C1-3 unbranched alkyl,
• and
• Prot represents a protective group.