Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors.

Basic Information

ID: ALA4680296

Journal: Bioorg Med Chem

Title: Design, synthesis and biological evaluation of novel thiazole-based derivatives as human Pin1 inhibitors.

Authors: Du L,Wang X,Cui G,Xu B

Abstract: Pin1 is a peptidyl prolyl cis-trans isomerase (PPIase) and inhibiting Pin1 is a potential way for discovering anti-tumor agents. With an aim to find potent Pin1 inhibitors with a novel scaffold, a series of thiazole derivatives with an alicyclic heterocycles on the 2-position were designed, synthesized and tested against human Pin1. Compound 9p bearing a 2-oxa-6-azaspiro [3,3] heptane moiety on the thiazole scaffold was identified as the most potent Pin1 inhibitor of this series with an IC value of 0.95 μM. The structure-activity relationship (SAR) and molecular modeling study indicated that introducing an alicyclic ring with an H-bond acceptor would be a viable way to improve the binding affinity.

CiteXplore: 33246256

DOI: 10.1016/j.bmc.2020.115878

Patent ID: ┄