ANTI-MITOTIC AGENTS WHICH INHIBIT TUBULIN POLYMERIZATION

摘要

3-Aroyl-2-arylbenzo[b]thiophenes derivatives of formula (I) are new: X = S, O, NH or CH2; R1-R4 = H, OH or 1-5C alkoxy; Z = CO, CH2, C2H2, CHOH or CHOCH3; Y = covalent bond, CH2 or CH2CH2; Ar, Ar1 = phenyl or naphthyl (both substituted with >= 1-5C alkoxy); provided that, when Ar1 = 3,4,5-trimethoxyphenyl or 4-methoxyphenyl, X = S, Z = CO, Y = covalent bond, R3 = methoxy, R1, R2, R4 = H, and Ar is substituted with a methoxy group, then Ar is substituted with >= 2 alkoxy groups. Also claimed are compounds (II) - (VII): Z1 = CO, Ar2, Ar3 = phenyl substituted with >= 1-5C alkoxy; provided that, when Ar3 = 3,4,5-trimethoxyphenyl or 4-methoxyphenyl, Z = CO, Y = covalent bond, R3 = methoxy, R1, R2, R4 = H, and Ar2 is substituted with a methoxy group, then Ar2 is substituted with at least two alkoxy groups; R11 = H or CH3O; R21 = H, CH3O or C2H5O; R31 = CH3O or C2H5O; R5, R7, R8, R41 = H, CH3O, C2H5O or F; R6 = H, CH3O, C2H5O, OH, F or N(CH3)2; X1 = CO, C(O)CH2, (CO)C2H4 or (CO)C2H2; X2 = S or SO; X3 = CHOH or CO; Ra, Rb = CH3O, NO2, NH2 or N3 and CH3O; and C2H2 is in E or Z configuration; provided that one of Ra and Rb is CH3O, and the other is NO2, NH2 or N3.