Discovery of orally active butyrolactam 11beta-HSD1 inhibitors.
A series of metabolically stable butyrolactam 11beta-HSD1 inhibitors have been synthesized and biologically evaluated. These compounds exhibit excellent HSD1 potency and HSD2 selectivity, 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
Kurukulasuriya
Ravi
R
Fung
Steven
S
Monzon
Katina
K
Chiou
William
W
Wang
Jiahong
J
Stolarik
Deanne
D
Imade
Hovis
H
Shapiro
Robin
R
Knourek-Segel
Victoria
V
Bush
Eugene
E
Wilcox
Denise
D
Nguyen
Phong T
PT
Brune
Michael
M
Jacobson
Peer
P
Link
J T
JT
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors*; D000284:Administration, Oral; D000818:Animals; D006801:Humans; D007769:Lactams / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology*; D024821:Metabolic Syndrome / Q000188:drug therapy; D051379:Mice
D007769:Lactams; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1