Design and synthesis of oxime ethers of alpha-acyl-beta-phenylpropanoic acids as PPAR dual agonists.
Oxime ethers of alpha-acyl-beta-phenylpropanoic acids were prepared to apply as PPARalpha and gamma dual agonists. Among them, compound 11l proved to exhibit potent in vitro activities with EC(50) of 19 and 13nM in PPARalpha and gamma, respectively. It showed better glucose lowering effects than rosiglitazone 1 and ameliorated the lipid profile like plasma triglyceride in db/db mice model.
Oon Han
Hee
H
Research and Development, LG Life Sciences, 104-1 Munji-dong, Yuseong-gu, Daejon 305-380, Republic of Korea.
Kim
Seung Hae
SH
Kim
Kyoung-Hee
KH
Hur
Gwong-Cheung
GC
Joo Yim
Hyeon
H
Chung
Hee-Kyung
HK
Ho Woo
Sung
S
Dong Koo
Ki
K
Lee
Chang-Seok
CS
Sung Koh
Jong
J
Kim
Geun Tae
GT
D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D001786:Blood Glucose / Q000378:metabolism; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007202:Indicators and Reagents; D008055:Lipids / Q000097:blood; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008958:Models, Molecular; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D010666:Phenylpropionates / Q000138:chemical synthesis* / Q000494:pharmacology*; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007202:Indicators and Reagents; D008055:Lipids; D047493:PPAR alpha; D047495:PPAR gamma; D010666:Phenylpropionates; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone