Discovery of potent and selective inhibitors of 11beta-HSD1 for the treatment of metabolic syndrome.
High throughput screening efforts have identified a novel class of dichloroaniline amide 11beta-HSD1 inhibitors. SAR studies initiated from dichloroaniline 4 focused on retaining the potency and selectivity profile of the lead.
Richards
Steven
S
Metabolic Disease Research, GPRD, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, IL 60064, USA. Steven.Richards@abbott.com
Sorensen
Bryan
B
Jae
Hwan-Soo
HS
Winn
Marty
M
Chen
Yixian
Y
Wang
Jiahong
J
Fung
Steven
S
Monzon
Katina
K
Frevert
Ernst U
EU
Jacobson
Peer
P
Sham
Hing
H
Link
J T
JT
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D002229:Carbenoxolone / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D024821:Metabolic Syndrome / Q000188:drug therapy*; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D000096926:Benzenesulfonamides
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D002229:Carbenoxolone; D004791:Enzyme Inhibitors; D010879:Piperazines; D013449:Sulfonamides; D013844:Thiazoles; C474501:3-chloro-2-methyl-N-(4-(2-(4-methyl-1-piperazinyl)-2-oxoethyl)-1,3-thiazol-2-yl)benzenesulfonamide; D000096926:Benzenesulfonamides