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Bioorg Med Chem Lett
; 28(3): 523-528, 2018 02 01.
Article
in English
| MEDLINE
| ID: mdl-29329659
ABSTRACT
Inspired by a rhodanine-based dual inhibitor of Bcl-xL and Mcl-1, a focused library of analogues was prepared wherein the rhodanine core was replaced with a less promiscuous thiazolidine-2,4-dione scaffold. Compounds were initially evaluated for their abilities to inhibit Mcl-1. The most potent compound 12b inhibited Mcl-1 with a Ki of 155â¯nM. Further investigation revealed comparable inhibition of Bcl-xL (Kiâ¯=â¯90â¯nM), indicating that the dual inhibitory profile of the initial rhodanine lead had been retained upon switching the heterocycle core.