Synthesis and structural activity relationship of 11beta-HSD1 inhibitors with novel adamantane replacements.
A series of structurally novel and metabolically stable bridged bicyclic carbocycle and heterocycle adamantane replacements have been synthesized and biologically evaluated. Several of these compounds exhibit excellent human and mouse 11beta-HSD1 potency and 11beta-HSD2 selectivity.
Yeh
Vince S C
VS
Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, AP-10,304B, Abbott Park, IL 60064, USA. vince.yeh@abbott.com
Kurukulasuriya
Ravi
R
Madar
David
D
Patel
Jyoti R
JR
Fung
Steven
S
Monzon
Katina
K
Chiou
William
W
Wang
Jiahong
J
Jacobson
Peer
P
Sham
Hing L
HL
Link
J T
JT
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000037:antagonists & inhibitors; D000218:Adamantane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000218:Adamantane