2-hydroxy-N-arylbenzenesulfonamides as ATP-citrate lyase inhibitors.
A novel series of 2-hydroxy-N-arylbenzenesulfonamides were identified to be ATP-citrate lyase (ACL) inhibitors with compound 9 displaying potent in vitro activity (IC(50)=0.13 microM). Chronic oral dosing of compound 9 in high-fat fed mice lowered plasma cholesterol, triglyceride, and glucose, as well as inhibited weight gain.
Li
James J
JJ
Bristol-Myers Squibb Pharmaceutical Research Institute, PO Box 5400, Princeton, NJ 08543-5400, USA. James.Li@bms.com
Wang
Haixia
H
Tino
Joseph A
JA
Robl
Jeffrey A
JA
Herpin
Timothy F
TF
Lawrence
R Michael
RM
Biller
Scott
S
Jamil
Haris
H
Ponticiello
Randy
R
Chen
Luping
L
Chu
Ching-hsuen
CH
Flynn
Neil
N
Cheng
Dong
D
Zhao
Rulin
R
Chen
Bangchi
B
Schnur
Dora
D
Obermeier
Mary T
MT
Sasseville
Vito
V
Padmanabha
Ramesh
R
Pike
Kristen
K
Harrity
Thomas
T
D001275:ATP Citrate (pro-S)-Lyase / Q000037:antagonists & inhibitors*; D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry*; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D051381:Rats; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
D019440:Anti-Obesity Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D013449:Sulfonamides; D014280:Triglycerides; D002784:Cholesterol; D001275:ATP Citrate (pro-S)-Lyase; D001554:Benzene