beta-Keto sulfones as inhibitors of 11beta-hydroxysteroid dehydrogenase type I and the mechanism of action.
The design, synthesis, and biological evaluation of beta-keto sulfones as 11beta-HSD1 inhibitors and the mechanism of inhibition are described here. This class of compounds is not active against 11beta-HSD2 and therefore may have therapeutic potential for metabolic syndrome and type 2 diabetes.
Xiang
Jason
J
Chemical and Screening Sciences, Wyeth Research, 200 Cambridge Park Drive, MA 02140, USA. jxiang@wyeth.com
Ipek
Manus
M
Suri
Vipin
V
Tam
May
M
Xing
Yuzhe
Y
Huang
Nelson
N
Zhang
Yanling
Y
Tobin
James
J
Mansour
Tarek S
TS
McKew
John
J
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000478:Alkylation; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004563:Electrochemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology*; D012997:Solvents; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D007659:Ketones; D012997:Solvents; D013450:Sulfones; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1