title: (2R)-2-methylchromane-2-carboxylic acids: discovery of selective PPARalpha agonists as hypolipidemic agents.
abstract: A SAR study was conducted on chromane-2-carboxylic acid toward selective PPARalpha agonisim. As a result, highly potent, and selective PPARalpha agonists were discovered. The optimized compound 43 exhibited robust lowering of total cholesterol levels in hamster and dog animal models.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000 Rahway, NJ 07065, USA. hiroo_koyama@merck.com
authors.forename: Hiroo
authors.initials: H
authors.lastname: Koyama
authors.forename: Julia K
authors.initials: JK
authors.lastname: Boueres
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Miller
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Karen L
authors.initials: KL
authors.lastname: MacNaul
authors.forename: Pei-ran
authors.initials: PR
authors.lastname: Wang
authors.forename: Marc C
authors.initials: MC
authors.lastname: Ippolito
authors.forename: Samuel D
authors.initials: SD
authors.lastname: Wright
authors.forename: Arun K
authors.initials: AK
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; D002264:Carboxylic Acids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D002839:Chromans / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D006224:Cricetinae; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D015394:Molecular Structure; D047493:PPAR alpha / Q000819:agonists*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013329:Structure-Activity Relationship
chemical_list: D002264:Carboxylic Acids; D002839:Chromans; D000960:Hypolipidemic Agents; D047493:PPAR alpha