Dihydro iso AC-4 and analogs: potent cytotoxic, inhibitors of tubulin polymerization

The present invention relates to compounds of formula (I): g id = "ID2932180-2" he = "" wi = "" file = "" img-format = "tif" />> wherein: - Ri, R2 and R4, independently of each other, a hydrogen atom or a methoxy group optionally substituted by one or more fluorine atoms, - R3 represents a methoxy group optionally substituted by one or more fluorine atoms, - a represents a ring selected from the group consisting of aryl and heteroaryl, which ring may be substituted or fused to a heterocycle, - X represents a nitrogen atom or a CH group, and - Z1 represents a hydrogen atom or a halogen atom , preferably fluorine, and - Z2 represents a hydrogen atom, a halogen atom, preferably fluorine, C1-C4 alkyl, aryl or -CN, -SO2NR12R13, -SO2R9, -COOR15 or -COR15 and their pharmaceutically acceptable salts, isomers and prodrugs thereof.