VARIOLIN DERIVATIVES AS ANTI-CANCER AGENTS

摘要

The invention provides variolin derivatives of formula (I), wherein: R1 and R2are each independently selected from the group consisting of H, OH, ORï, SH,SRï, SORï, SO2Rï, NO2, NH2, NHRï, N(Rï)2, NHCORï, N(CORï)2, NHSO2Rï, CN,halogen, C(=O)H, C(=O)Rï, CO2H, CO2Rï, C1-C12 alkyl, C1-C12 haloalkyl, C2-C12alkenyl, C2-C12 alkynyl, substituted or unsubstituted aryl, substituted orunsubstituted aralkyl and substituted or unsubstituted heteroaromatic; and R3is selected from the group consisting of H, OH and OMe; wherein the or eachgroup Rï is independently selected from the group consisting of OH, C1-C12alkyl, C1-C12 haloalkyl, C2-C12 alkenyl, C2-C12 alkynyl, substituted orunsubstituted aryl, substituted or unsubstituted aralkyl, substituted orunsubstituted arylalkenyl and substituted or unsubstituted heteroaromatic, andwherein the group R1, R2 or R3 is a group of formula N(Rï)2 or N(CORï)2, eachof the Rï groups may be the same or different, or the two Rï groups, togetherwith the nitrogen atom to which they are attached, may form a 5-14 memberedheterocyclic ring. These compounds display activity against a range ofmammalian cancer cell lines. New synthetic routes to new and known variolincompounds, together with novel intermediates, are also disclosed. Newantitumour activity of known variolin compounds is also described.