Patent ID: 6342487
Filing Date: 2002-01-29
Classification: A61K,A61P,Y10S

Abstract:
A composition comprising at least one topoisomerase I inhibitor and at least one farnesyl transferase inhibitor selected from the compounds of formula (I): in which:Ar is a phenyl radical substituted by one or more identical or different atoms or radicals, selected from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkenyl radicals containing 2 to 4 carbon atoms, hydroxyl, mercapto, alkylthio, alkylsulfonyl and alkylsulfinyl, amino, alkylamino and dialkylamino, formyl, alkylcarbonyl, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl and dialkylcarbamoyl, cyano and trifluoromethyl radicals, and alkoxy radicals containing 1 to 4 carbon atoms, whose alkyl portion is optionally perhalogenated; a phenyl radical fused to a heterocycle of 4 to 7 members containing one or more heteroatoms selected from oxygen, nitrogen and sulfur atoms; a polycyclic aromatic radical; or a heterocyclic aromatic radical of 5 to 12 chain members incorporating one or more heteroatoms selected from oxygen, nitrogen and sulfur atoms, linked to the fused ring by a carbon-carbon bond, said radical being optionally substituted, by one or more identical or different atoms or radicals, selected from halogen atoms and alkyl and alkenyl radicals containing 2 to 4 carbon atoms, hydroxyl, alkoxy radicals containing 1 to 4 carbon atoms, mercapto, alkylthio, alkylsulfonyl and alkylsulfinyl, amino, alkylamino and dialkylamino, formyl, alkylcarbonyl, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl and dialkylcarbamoyl, cyano and trifluoromethyl radicals; R is a radical of formula â€”(CH2)mâ€”X1â€”(CH2)nâ€”Z in which X1 is a single bond or an oxygen or sulfur atom, m is a whole number equal to 0 or 1, n is a whole number equal to 0, 1 or 2, or one or more methylene radicals which are optionally substituted by a carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, amino, alkylamino or dialkylamino radical, Z is a carboxyl radical; a COOR6 radical, in which R6 is a linear alkyl radical containing 1 to 3 carbon atoms, or a branched alkyl radical containing 3 carbon atoms; or a radical of formula CON(R7)(R8) in which R7 is a hydrogen atom or a linear alkyl radical containing 1 to 6 carbon atoms or a branched alkyl radical containg 3 to 6 carbon atoms; and R8 is a hydrogen atom; a hydroxyl radical; an arylsulfonyl radical, optionally substituted by one or more identical or different atoms or radicals, selected from halogen atoms and alkyl and alkoxy radicals; a heterocycle of 5 to 7 members incorporating one or more heteroatoms selected from nitrogen, oxygen and sulfur atoms, wherein said heterocycle can be linked by a heteroatom; an amino radical optionally substituted by one or two identical or different radicals selected from the radicals alkyl containing 1 to 4 carbon atoms, aryl, optionally substituted by one or more identical or different radicals, selected from alkyl and alkoxy radicals, wherein said alkyl radicals contain 1 to 4 carbon atoms, heterocyclyl of 5 to 7 chain members and containing one or more heteroatoms selected from nitrogen, oxygen and sulfur atoms, and arylcarbonyl, optionally substituted by one or more identical or different radicals, selected from alkyl and alkoxy radicals, wherein said alkyl radicals contain 1 to 4 carbon atoms; an alkoxy radical containing 1 to 6 carbon atoms in a linear or branched chain optionally substituted by a phenyl radical; or a linear alkyl radical containing 1 to 6 carbon atoms or a branched alkyl radical containing 3 to 6 carbon atoms, each of said radicals being optionally substituted by an amino, alkylamino, dialkylamino or hydroxyl radical, an alkoxy radical containing 1 to 4 carbon atoms, a mercapto, alkylthio, alkoxycarbonyl, carboxyl, cyano, a mono- or polycyclic aromatic radical having 5 to 12 chain members, incorporating or not incorporating one or more heteroatoms selected from oxygen, nitrogen and optionally substituted sulfur atoms, or a phenyl radical optionally substituted by one or more halogen atoms or by one or more hydroxyl, amino ortrifluoromethyl groups, or by one or more C2 to C4 alkyl or alkenyl, alkoxy, alkylthio, alkylamino, alkylcarbonyl or alkoxycarbonyl radicals, a carbamoyl, alkylcarbamoyl or dialkylcarbamoyl whose alkyl part is C1 to C8, formyl or a 1- or 2-naphthyl radical; or Z is a PO(OR9)2 radical in which R9 is a hydrogen atom or a linear alkyl radical containing 1 to 6 carbon atoms or a branched alkyl radical containing 3 to 6 carbon atoms, or an â€”NHâ€”COâ€”T radical in which T is a hydrogen atom or a linear alkyl radical containing 1 to 6 carbon atoms or a branched alkyl radical containing 3 to 6 carbon atoms, each of said radicals being optionally substituted by an amino, carboxyl, alkoxycarbonyl, hydroxyl, alkoxy, mercapto or alkylthio radical, or having, as counterion, an anion;R1 and R2, which are identical or different, are a hydrogen atom, a halogen or an alkyl radical, an alkoxy radical, each optionally substituted by a dialkylamino radical of which each alkyl part contains 1 to 4 carbon atoms or forms, with the nitrogen atom, a saturated heterocycle containing 5 or 6 chain members, an alkylthio radical, an alkoxycarbonyl radical, or when situated ortho with respect to one another, R1 and R2 may form a saturated or unsaturated heterocycle containing 1 or 2 heteroatoms selected from nitrogen and oxygen, optionally substituted by a halogen atom or by an alkyl or alkoxy radical; R3 and R4, which are identical or different, are a hydrogen or halogen atom or an alkyl, hydroxyl, alkoxy, alkylcarbonyloxy, mercapto, alkylthio, alkylsulfonyl or alkylsulfinyl, amino, alkylamino or dialkylamino, alkoxycarbonylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl or dialkylcarbamoyl, formyl, alkylcarbonyl, cyano or trifluoromethyl radical; R5 is a hydrogen atom or an alkyl radical, or an alkylthio radical; X is an oxygen or sulfur atom or an â€”NHâ€”, â€”COâ€”, methylene, or alkene-1-diyl group; and Y is an oxygen or sulfur atom; in a racemic form, in the form of an optical isomer or in the form of a salt thereof.