Discovery of 4-(dimethylamino)quinazolines as potent and selective antagonists for the melanin-concentrating hormone receptor 1

A series of 4-(dimethylamino)quinazoline based antagonists of the melanin-concentrating hormone receptor 1 (MCH-R1) is described. This series was derived from a lead compound, AR129330, identified by HTS of a GPCR-directed library using a functional assay with a constitutively activated (CART) form of the receptor. The preliminary optimization resulted in the identification of compounds 20, 21, and 23.

Graphical abstractHigh-throughput screening of our in-house GPCR-directed library uncovered a series of 4-(dimethylamino)quinazolines as melanin-concentrating hormone receptor 1 (MCH-R1) antagonists (e.g., AR129330). The synthesis and early SAR investigation of this series are reported.Figure optionsDownload full-size imageDownload as PowerPoint slide