168080-72-6Relevant academic research and scientific papers
Perhydroquinolylbenzamides as novel inhibitors of 11β-hydroxysteroid dehydrogenase type 1
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.
, p. 6696 - 6712 (2007/10/03)
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. Analogues which showed >50% inhibition of 11β-HSD1 at 1 μM in an cellular assay were screened in an ADX mouse model. A maximal response of >70% reduction of liver corticosterone levels was observed for three compounds; 9m, 25 and 49.
