Synthesis, kinase inhibitory potencies and in vitro antiproliferative activity of isoindigo and 7′-azaisoindigo derivatives substituted by Sonogashira cross-coupling

In the course of structure-activity relationship studies we were interested in the synthesis of isoindigo and 7'-azaisoindigo derivatives substituted at the N-1 position by a 1-(2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl), at the 5'-position by various chains introduced by Sonogashira cross-coupling and substituted or not at the 5-position by a bromine atom. To get an insight into the substitution pattern required for the best biological potencies, their kinase inhibitory potencies and their in vitro anti-proliferative activities were evaluated. The derivatives were tested toward four protein kinases (CDK5/p25, GSK3, CK1, Dyrk1A) and their in vitro anti proliferative activity was tested against two human myeloid leukaemia cell lines (K562 and HL60). (C) 2009 Elsevier Masson SAS. All rights reserved.