Synthesis and optimization of arylsulfonylpiperazines as a novel class of inhibitors of 11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1).
The synthesis and SAR of a series of arylsulfonylpiperazine inhibitors of 11beta-HSD1 are described. Optimization rapidly led to potent, selective, and orally bioavailable inhibitors demonstrating efficacy in a cynomolgus monkey ex vivo enzyme inhibition model.
Sun
Daqing
D
Wang
Zhulun
Z
Cardozo
Mario
M
Choi
Rebekah
R
Degraffenreid
Michael
M
Di
Yongmei
Y
He
Xiao
X
Jaen
Juan C
JC
Labelle
Marc
M
Liu
Jinsong
J
Ma
Ji
J
Miao
Shichang
S
Sudom
Athena
A
Tang
Liang
L
Tu
Hua
H
Ursu
Stefania
S
Walker
Nigel
N
Yan
Xuelei
X
Ye
Qiuping
Q
Powers
Jay P
JP
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D017739:Arylsulfonic Acids / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology; D001682:Biological Availability; D002460:Cell Line; D018360:Crystallography, X-Ray; D004795:Enzyme Stability / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008252:Macaca fascicularis; D051379:Mice; D010879:Piperazines / Q000138:chemical synthesis* / Q000145:classification / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D017739:Arylsulfonic Acids; D010879:Piperazines; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1