title: Design and synthesis of potent and subtype-selective PPARalpha agonists.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065, USA. ranjit_desai@merck.com
authors.forename: Ranjit C
authors.initials: RC
authors.lastname: Desai
authors.forename: Edward
authors.initials: E
authors.lastname: Metzger
authors.forename: Conrad
authors.initials: C
authors.lastname: Santini
authors.forename: Peter T
authors.initials: PT
authors.lastname: Meinke
authors.forename: James V
authors.initials: JV
authors.lastname: Heck
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Karen L
authors.initials: KL
authors.lastname: MacNaul
authors.forename: Tian-quan
authors.initials: TQ
authors.lastname: Cai
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Wright
authors.forename: Arun
authors.initials: A
authors.lastname: Agrawal
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
authors.forename: Soumya P
authors.initials: SP
authors.lastname: Sahoo
mesh_terms: 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
chemical_list: D000960:Hypolipidemic Agents; D047493:PPAR alpha