VARIOLIN DERIVATIVES AS ANTI-CANCER AGENTS

The invention provides variolin derivatives of formula (I), wherein: R1 and R2 are each independently selected from the group consisting of H, OH, OR, SH, SR, SOR, SO2R, NO2, NH2, NHR, N(R)2, NHCOR, N(COR)2, NHSO2R, CN, halogen, C(-O)H, C(-O)R, CO2H, CO2R, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted aralkyl and substituted or unsubstituted heteroaromatic; and R3 is selected from the group consisting of H, OH and OMe; wherein the or each group R is independently selected from the group consisting of OH, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, substituted or unsubstituted aryl, substituted unsubstituted aralkyl, substituted or unsubstituted arylalkenyl and substituted or unsubstituted heteroaromatic, and wherein the group R1, R2 or R3 is a group of formula N(R)2 or N(COR)2, each of the R groups may be the same or different, or the two R groups, together with the nitrogen atom to which they are attached, may form a 5-14 membered heterocyclic ring. These compounds display activity against a range of mammalian cancer cell lines. New synthetic routes to new and known variolin compounds, together with novel intermediates, are also disclosed. New antitumour activity of known variolin compounds is also described.