The discovery of azepane sulfonamides as potent 11beta-HSD1 inhibitors.
Discovery of a series of azepine sulfonamides as potent inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is described. SAR studies at the 4-position of the azepane ring have resulted in the discovery of a very potent compound 30 which has an 11beta-HSD1 IC(50) of 3.0nM.
Neelamkavil
Santhosh F
SF
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA. santhosh.neelamkavil@spcorp.com
Boyle
Craig D
CD
Chackalamannil
Samuel
S
Greenlee
William J
WJ
Zhang
Lili
L
Terracina
Giuseppe
G
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000893:Anti-Inflammatory Agents; D001381:Azepines; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1