Perhydroquinolylbenzamides as novel inhibitors of 11β-hydroxysteroid dehydrogenase type 1

…, JL Stanton, AD Neubert, N Marcopulos…

Index: Coppola, Gary M.; Kukkola, Paivi J.; Stanton, James L.; Neubert, Alan D.; Marcopulos, Nicholas; Bilci, Natalie A.; Wang, Hua; Tomaselli, Hollis C.; Tan, Jenny; Aicher, Thomas D.; Knorr, Douglas C.; Jeng, Arco Y.; Dardik, Beatriz; Chatelain, Ricardo E. Journal of Medicinal Chemistry, 2005 , vol. 48, # 21 p. 6696 - 6712

Full Text: HTML

Citation Number: 56

Abstract

High-throughput screening identified 5 as a weak inhibitor of 11β-HSD1. Optimization of the structure led to a series of perhydroquinolylbenzamides, some with low nanomolar inhibitory potency. A tertiary benzamide is required for biological activity and substitution of the terminal benzamide with either electron-donating or-withdrawing groups is tolerated. The majority of the compounds show selectivity of> 20 to> 700-fold over 11β-HSD2. ...