- Discovery of novel, potent benzamide inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) exhibiting oral activity in an enzyme inhibition ex vivo model
-
We report the discovery of potent benzamide inhibitors of 11β-hydroxysteroid dehydrogenase (11β-HSD1). The optimization and correlation of in vitro and in vivo metabolic stability will be described. Through modifications to our initial lead 2, we discovered pyridyl compound 13. This compound has a favorable pharmacokinetic profile across three species and showed a dose-dependent decrease in adipose 11β-HSD1 activity in a monkey ex vivo pharmacodynamic model.
- Julian, Lisa D.,Wang, Zhulun,Bostick, Tracy,Caille, Seb,Choi, Rebekah,DeGraffenreid, Michael,Di, Yongmei,He, Xiao,Hungate, Randall W.,Jaen, Juan C.,Liu, Jinsong,Monshouwer, Mario,McMinn, Dustin,Rew, Yosup,Sudom, Athena,Sun, Daqing,Tu, Hua,Ursu, Stefania,Walker, Nigel,Yan, Xuelei,Ye, Qiuping,Powers, Jay P.
-
experimental part
p. 3953 - 3960
(2009/04/10)
-
- Benzamide derivatives and uses related thereto
-
Benzamide derivatives of formula I are described and have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorders:
- -
-
Page/Page column 25
(2008/06/13)
-
- Benzamide derivatives and uses related thereto
-
Benzamide derivatives of formula I are described and have therapeutic utility, particularly in the treatment of diabetes, obesity and related conditions and disorders: wherein R1, R2, R3, R4, R5, R6, R7, R8, and n are as defined herein.
- -
-
Page/Page column 41
(2008/06/13)
-
- Benzamide derivatives and uses related thereto
-
Benzamide derivatives of formulae I and II, and pharmaceutically acceptable salts, solvates, stereoisomers, and prodrugs thereof, and pharmaceutical compositions comprising the same, are described and have therapeutic utility, particularly in the treatment of diabetes, obesity, and related conditions and disorders: wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, R11, and R12 are defined as provided herein.
- -
-
Page/Page column 49-50
(2008/06/13)
-