Imidazole derivatives having an inhibitory activity for farnesyl transferase and process for preparation thereof

A compound represented by the following formula (8)

• wherein
• n1 represents an integer of 1 to 4,
• A represents hydrogen;
• straight-chain or branched C1-C10-alkyl which may be optionally substituted by C3-C7-cycloalkyl or lower alkoxy;
• or a radical selected from the following group:
• wherein
• R1 and R1′ independently of one another represent hydrogen, cyano, nitro, hydroxycarbonyl, aminocarbonyl, aminothiocarbonyl, lower alkoxy, phenoxy, phenyl, benzyloxy, or lower alkyl which may be optionally substituted by C3-C6-cycloalkyl,
• R2 represents hydrogen or lower alkyl, or represents —E—F wherein E is —CH2—, —C(O)— or —S(O)2— and F is hydrogen, lower alkyl which may be optionally substituted by phenoxy or biphenyl;
• lower alkoxy which may be optionally substituted by aryl;
• phenyl;
• benzyl;
• benzyloxy;
• or amino which may be optionally substituted by lower alkyl, benzyl, or C5-C6-cycloalkyl,
• R3 represents hydrogen, lower alkyl or phenyl,
• R4 represents a radical selected from the following group:
• wherein
• n2 and n3 independently of one another denote 0, 1, 2, 3 or 4,
• R5 and R9 independently of one another represent hydrogen, lower alkyl, lower alkoxy, phenoxy, phenyl, hydroxy or halogen,
• R6 and R8 independently of one another represent hydrogen, lower alkyl, lower alkoxy, phenoxy, phenyl, cyano, hydroxy or halogen,
• R7 represents hydrogen;
• lower alkyl which may be optionally substituted by C3-C6-cycloalkyl;
• lower alkoxy;
• hydroxy;
• C3-C6-cycloalkyl;
• di(lower alkyl)amino;
• phenyl;
• phenoxy;
• or halogen,
• R10 represents hydrogen, lower alkyl or lower alkoxy,
• Y represents a radical selected from the following group:
• wherein
• X represents O or S,
• B represents hydrogen, or lower alkyl which may be optionally substituted by hydroxy, mercapto, lower alkoxy, lower alkylthio or aryl,
• C represents hydrogen, or lower alkyl which may be optionally substituted by aryl;
• or represents a radical selected from the following group:
• wherein
• R11 and R12 independently of one another represent hydrogen, lower alkyl, lower alkoxy, halogen, cyano, hydroxycarbonyl, aminocarbonyl, aminothiocarbonyl, hydroxy, phenyl, or phenoxy,
• R13 and R14 independently of one another represent hydrogen, lower alkyl, aryl or —(CH2)n4—X—R15 wherein X is defined as previously described, n4 is an integer of 2 to 4 and R15 is lower alkyl,
• D represents amino acid residue or lower alkyl ester of amino acid residue;
• or represents a radical selected from the following group:
• wherein
• R10 is defined as previously described,
• Q represents O, S, S═O Or SO2,
• Z represents O, S, S═O, SO2, C═O or C═S, or represents CH—R20 or N—R20 (wherein R20 is hydrogen, lower alkyl or hydroxy),
• n5 denotes an integer of 1 to 3,
• R16 and R17 independently of one another represent hydrogen;
• aryl;
• lower alkyl which may be optionally substituted by aryl or cyanoaryl;
• or —(CH2)n4—Q—R10 wherein n4, Q and R10 are defined as previously described,
• R18 and R19 independently of one another represent hydrogen;
• halogen;
• cyano;
• lower alkyl;
• lower alkoxy;
• alkoxyalkyl;
• alkylthio;
• hydroxycarbonyl;
• aminocarbonyl;
• aminothiocarbonyl;
• alkylsulfonyl;
• alkylthioalkyl;
• alkylthioalkyloxy;
• aryl;
• or oxy, thio, sulfonyl or lower alkyl substituted by aryl,
• G represents a radical selected by the following group:
• wherein
• R11 and R12 are defined as previously described,
• I represents lower alkoxy, or represents a radical selected from the following group:
• wherein
• R16, R17 and Z are defined as previously described,
• L represents a radical selected from the following group:
• wherein Z and Q are defined as previously described,
• provided that (1H) n2 is other O when R3 is hydrogen, and
• or a pharmaceutically acceptable salt or isomer thereof.