Design and synthesis of potent and subtype-selective PPARalpha agonists.
Beginning with a moderately potent PPARgamma agonist 9, a series of potent and highly subtype-selective PPARalpha agonists was identified through a systematic SAR study. Based on the results of the efficacy studies in the hamster and dog models of dyslipidemia and the desired pharmacokinetic data, the optimized compound 39 was selected for further profiling.
Desai
Ranjit C
RC
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. ranjit_desai@merck.com
Metzger
Edward
E
Santini
Conrad
C
Meinke
Peter T
PT
Heck
James V
JV
Berger
Joel P
JP
MacNaul
Karen L
KL
Cai
Tian-quan
TQ
Wright
Samuel D
SD
Agrawal
Arun
A
Moller
David E
DE
Sahoo
Soumya P
SP
D000818:Animals; D006224:Cricetinae; D004285:Dogs; D015195:Drug Design; D050171:Dyslipidemias / Q000188:drug therapy*; D000882:Haplorhini; D000960:Hypolipidemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists* / Q000235:genetics; D051381:Rats; D013329:Structure-Activity Relationship; D015533:Transcriptional Activation
D000960:Hypolipidemic Agents; D047493:PPAR alpha