Azabicyclic sulfonamides as potent 11beta-HSD1 inhibitors.
Inhibition of 11beta-HSD1 has demonstrated potential in the treatment of various components of metabolic syndrome. We wish to report herein the discovery of novel azabicyclic sulfonamide based 11beta-HSD1 inhibitors. Highly potent compounds exhibiting inhibitory activities at both human and mouse 11beta-HSD1 were identified. Several compounds demonstrated significant in vivo activity in the mouse cortisone challenge assay.
Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. unmesh.shah@spcorp.com
Unmesh
U
Shah
Craig D
CD
Boyle
Samuel
S
Chackalamannil
Hana
H
Baker
Timothy
T
Kowalski
Julie
J
Lee
Giuseppe
G
Terracina
Lili
L
Zhang
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D053961:Azabicyclo Compounds / Q000737:chemistry*; D003348:Cortisone / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D053961:Azabicyclo Compounds; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D013449:Sulfonamides; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D003348:Cortisone