Bioorganic & Medicinal Chemistry 2012-12-01

Synthesis and structure based optimization of 2-(4-phenoxybenzoyl)-5-hydroxyindole as a novel CaMKII inhibitor.

Masafumi Komiya, Shigehiro Asano, Nobuyuki Koike, Erina Koga, Junetsu Igarashi, Shogo Nakatani, Yoshiaki Isobe

Index: Bioorg. Med. Chem. 20(23) , 6840-7, (2012)

Full Text: HTML

Abstract

Based on 2-(4-phenoxybenzoyl)-5-hydroxyindole (2), a novel structural class of CaMKII inhibitors were synthesized and further optimized. The strong acidity of the hydroxyl group and the lipophilic group at the 4 and 6-positions were found to be necessary for strong CaMKII inhibition. Compound 25 was identified as a promising compound with 50-fold more potent inhibitory activity for CaMKII than 2. Compound 25 also showed high selectivity for CaMKII over off-target kinases.Copyright © 2012 Elsevier Ltd. All rights reserved.