Cyclobutene derivatives, their preparation and their therapeutic uses

A method of reducing the cholesterol level in a human having or susceptible to a high blood cholesterol level, which comprises administering to said human an effective dose of an inhibitor or an ileal bile acid transporter selected from the group consisting of compounds of formula (I):

• wherein:
• R1 represents an unsubstituted cycloalkyl group, an unsubstituted aryl group, an unsubstituted heterocyclic group, a cycloalkyl group substituted by at least one of substituents α and β defined below, an aryl group substituted by at least one of substituents α and β defined below, or a heterocyclic group substituted by at least one of substituents α and β defined below;
• R2 represents an unsubstituted cycloalkyl group, an unsubstituted aryl group, an unsubstituted heterocyclic group, a cycloalkyl group substituted by at least one of substituents α defined below, an aryl group substituted by at least one of substituents α defined below, or a heterocyclic group substituted by at least one of substituents α defined below;
• R3 and R4 are the same as or different from each other and each represents a hydrogen atom or one of substituents α defined below;
• A represents a group of formula (A-1):
• wherein:
• R5 represents a hydrogen atom, a hydroxy group or a lower alkyl group,
• R6 represents a hydroxy group, a lower alkoxy group, a lower alkylthio group or an amine residue,
• X and Y are the same as or different from each other and each represents an oxygen atom or a sulfur atom, and
• Z represents a direct single bond between the nitrogen atom and the benzene ring in formula (I), or an alkylene group having from 1 to 6 carbon atoms,
• G represents a single bond, an unsubstituted alkylene group having from 1 to 6 carbon atoms or an alkylene group having from 1 to 6 carbon atoms and substituted by at least one of substituents γ, defined below;
• the broken line represents a single or double bond;
• when the broken line represents a double bond,
• D represents a carbon atom;
• and
• E represents an ═N—O— group;
• when the broken line represents a single bond,
• D represents a CH group or a nitrogen atom, and
• E represents an oxygen atom, a sulfur atom, an —NH— group or a —CO— group;
• said substituents α are selected from the groups consisting of halogen atoms, hydroxy groups, cyano groups, nitro groups, lower alkyl groups, lower haloalkyl groups, lower alkoxy groups, lower alkylthio groups, amino groups, lower monoalkylamino groups and di(lower alkyl)amino groups;
• said substituents β are selected from the group consisting of carboxy groups, lower alkoxycarbonyl groups, carbamoyl groups, lower monoalkylcarbamoyl groups, di(lower alkyl)carbamoyl groups, nitro groups, unsubstituted cycloalkyl groups, unsubstituted aryl groups, unsubstituted aryloxy groups, unsubstituted aralkyloxy groups, unsubstituted arylthio groups and cycloalkyl, aryl, aryloxy, aralkyloxy and arylthio groups each substituted by at least one of said substituents α;
• said substituents γ are selected from the group consisting of hydroxy groups, oxo groups, unsubstituted cycloalkyl groups, unsubstituted aryl groups, unsubstituted heterocyclic groups, cycloalkyl groups substituted by at least one of said substituents α and β, aryl groups substituted by at least one of said substituents α and β, and heterocyclic groups substituted by at least one of said substituents α and β;
• said cycloalkyl groups are optionally fused to an aryl group;
• said heterocyclic groups and are optionally fused to an aryl group;
• or a pharmaceutically acceptable salt, ester or other derivative thereof.