Bis-aryl triazoles as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.
3-Aryl-5-phenyl-(1,2,4)-triazoles were identified as selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). They are active in both in vitro and an in vivo mouse pharmacodynamic (PD) model. The synthesis and structure activity relationships are presented.
Aster
Susan D
SD
Department of Medicinal Chemistry, Merck & Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. susan_aster@merck.com
Graham
Donald W
DW
Kharbanda
Divya
D
Patel
Gool
G
Ponpipom
Mitree
M
Santorelli
Gina M
GM
Szymonifka
Michael J
MJ
Mundt
Steven S
SS
Shah
Kashmira
K
Springer
Marty S
MS
Thieringer
Rolf
R
Hermanowski-Vosatka
Anne
A
Wright
Samuel D
SD
Xiao
Jianying
J
Zokian
Hratch
H
Balkovec
James M
JM
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000818:Animals; D001665:Binding Sites; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D006841:Hydrocarbons, Aromatic / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use; D007004:Hypoglycemic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D020128:Inhibitory Concentration 50; D024821:Metabolic Syndrome / Q000188:drug therapy*; D051379:Mice; D008956:Models, Chemical; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use
D004791:Enzyme Inhibitors; D006841:Hydrocarbons, Aromatic; D007004:Hypoglycemic Agents; D014230:Triazoles; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1