Synthesis and biological evaluation of heterocycle containing adamantane 11beta-HSD1 inhibitors.
A series of metabolically stable adamantane amide 11beta-HSD1 inhibitors have been synthesized and biologically evaluated. These compounds exhibit excellent HSD1 potency and HSD2 selectivity and good pharmacokinetic and pharmacodynamic profiles.
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
Patel
Jyoti R
JR
Yong
Hong
H
Kurukulasuriya
Ravi
R
Fung
Steven
S
Monzon
Katina
K
Chiou
William
W
Wang
Jiahong
J
Stolarik
Deanne
D
Imade
Hovis
H
Beno
David
D
Brune
Michael
M
Jacobson
Peer
P
Sham
Hing
H
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*; D006571:Heterocyclic Compounds / 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; D006571:Heterocyclic Compounds; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D000218:Adamantane