2-aryl-indolyl maleimides - novel and potent inhibitors of protein kinase C

A new class of protein kinase C (PKC) inhibitors is described. These inhibitors were derived from the familiar bis-indolyl maleimide series of inhibitors through a structural rearrangement involving transfer of one aryl ring from the maleimide moiety to the C-2 position of the indole ring remaining attached to that moiety. The resulting compounds are among the most potent known inhibitors of PKC and also show good selectivity for PKC in relation to other kinases. The lead compound in this series possesses antitumor activity in several in vitro and in vivo models.