3‐(7‐Azaindolyl)‐4‐indolylmaleimides as a novel class of mutant isocitrate dehydrogenase‐1 inhibitors: Design, synthesis, and biological evaluation. Issue 10 (16th August 2018) - Hu, Yuanyuan
Abstract: A series of 3‐(7‐azainodyl)‐4‐indolylmaleimides was designed, synthesized, and evaluated for their isocitrate dehydrogenase 1 (IDH1)/R132H inhibitory activities. Many compounds such as11a, 11c, 11e, 11g, and11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the wild‐type IDH1. Evaluation of the biological activities at the cellular level showed that compounds11a, 11c, 11e, 11g, and11s could effectively suppress the production of 2‐hydroxyglutaric acid in U87MG cells expressing IDH1/R132H. Preliminary structure–activity relationship (SAR) and molecular modeling studies were discussed based on the experimental data obtained. These findings may provide new insights into the development of novel IDH1/R132H inhibitors. Abstract : A series of 3‐(7‐azainodyl)‐4‐indolylmaleimides was designed, synthesized, and evaluated for their IDH1 mutant R132H inhibitory activities. Many compounds such as11a, 11c, 11e, 11g, and11s exhibited favorable inhibitory effects on IDH1/R132H and were highly selective against the IDH1 wild‐type. Compounds11a, 11c, 11e, 11g, and11s could effectively suppress the production of 2‐hydroxyglutaric acid in U87MG cells expressing IDH1/R132H.