Synthesis and evaluation of novel indole derivatives as AKT inhibitors

2^nd International Conference on Medicinal Chemistry & Computer Aided Drug Designing

October 15-17, 2013 Hampton Inn Tropicana, Las Vegas, NV, USA

Linna Zhang, Dezhi Yang, Peng Wang, Jianzhen Liu and Guisen Zhao

Accepted Abstracts: Med chem

Abstract :

We described the discovery and synthesis of a new series of 1,2,4,7-tetra-substituted indole derivatives as novel AKT inhibitors by optimization of a weak hit methyl 4-(2-aminoethoxy)-1H-indole-2-carboxylate. Both representative compounds 8a and 8o showed the most potent inhibitory activity against AKT 1 with inhibition rates of 72.5% and 78.6% at 10 nM concentrations, respectively. Moreover compounds 8a and 8o also potently inhibited the phosphorylation of downstream GSK3 protein and displayed strongly anti-proliferative activity in prostate cancer cell line. Keywords: AKT inhibitors, GSK3 β , Inhibition rate, Tetra-substituted indoles.