Iso CA-4 and analogues thereof as potent cytotoxic agents inhibiting tubuline polymerization

A compound of the following formula (I):

• wherein:
• R1, R2 and R3 represent independently of each other a methoxy group optionally substituted with one or more fluorine atoms,
• R4 represents a hydrogen atom,
• R5 and R6 are identical and each represents a hydrogen or fluorine atom,
• A is a 1,3-benzodioxolyl, chromanyl or chromenyl group, said group being optionally substituted with one or more C1-C4 alkyl groups, or
• a phenyl or naphtyl group, said group being optionally substituted with one or more groups selected from halogens, —B(OH)2 groups, C1-C4 alkyls, C2-C4 alkenyls, C2-C4 alkynyls, aryl, heteroaryl, —COOH, —NO2, methylenedioxy, —NR7R8, —NHCOR7, —CONR7R8, —NHCOOR9, —OSi(C1-C4 alkyl)3, —NHSO2R9, C1-C4 alkoxy optionally substituted with one or more fluorine atoms, OCONR7R8, —OSO2CF3, —OSO2R9, —SO2R9, —OSO3H, —OPO(OR10)2, —ONR7R8, —OR11, —SO2NR12R13, —SO2NHCOR14, —OCOR15, —OCOOR16, —SR17, OCO(CH2)nC6H4N[(CH2)mCl]2 with n=1 to 4 and m=1 to 3, and a residue of a molecule with antitumoral activity, said molecule comprising a COOH function in order to bound said molecule to the phenyl or naphtyl group via an ester or amide bond,
• wherein:
• R7 and R8 represent independently of each other, a hydrogen atom or a C1-C4 alkyl, aryl or heteroaryl group,
• R9 represents a C1-C4 alkyl, aryl or heteroaryl group,
• R10 represents a hydrogen atom or a C1-C4 alkyl group or a benzyl group,
• R11 represents a hydrogen atom, an O-protective group, a sugar selected from glucose, mannose, arabinose or galactose, an aminosugar or an amino acid, the free OH and HN2 groups of sugars, aminosugars and amino acids may optionally be substituted with an O-protective and N-protective group, respectively,
• R12 and R13 represent independently of each other a hydrogen atom, a C1-C4 alkyl group, an aryl or heteroaryl group,
• —COR14 represents the remainder of an amino acid molecule bound to the —SO2NH-group, or R14 represents a C1-C4 alkyl group,
• R15 represents a hydrogen atom, a C1-C4 alkyl, aryl or heteroaryl group, or a (CH2)mCO2H or —(CH2)mNR7R8 group with m=1 to 3,
• R16 represents a C1-C4 alkyl, aryl or heteroaryl group or a —(CH2)mCO2H or —(CH2)mNR7R8 group with m=1 to 3, and
• R17 represents a hydrogen atom or a C1-C4 alkyl or aryl group, as well as its pharmaceutically acceptable salts, excluding the following compound: