title: Phenylacetic acid derivatives as hPPAR agonists.
abstract: Beginning with the weakly active lead structure 1, a new series of hPPAR agonists was developed. In vivo glucose and triglyceride lowering activity was obtained by homologation and oxamination to 3, then conversion to substituted benzisoxazoles 4 and 5. Further manipulation afforded benzofurans 6 and 7. Compound 7 was of comparable potency as a glucose and triglyceride lowering agent in insulin resistant rodents to BRL 49653.
authors.affiliation: Department of Basic Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. conrad_santini@merck.com
authors.forename: Conrad
authors.initials: C
authors.lastname: Santini
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Berger
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Ralph
authors.initials: R
authors.lastname: Mosley
authors.forename: Karen
authors.initials: K
authors.lastname: MacNaul
authors.forename: Joel
authors.initials: J
authors.lastname: Berger
authors.forename: Thomas
authors.initials: T
authors.lastname: Doebber
authors.forename: Margaret
authors.initials: M
authors.lastname: Wu
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
authors.forename: Richard L
authors.initials: RL
authors.lastname: Tolman
authors.forename: Soumya P
authors.initials: SP
authors.lastname: Sahoo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D010648:Phenylacetates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011924:Rats, Zucker; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D000077154:Rosiglitazone; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000819:agonists*; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D010648:Phenylacetates; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D014280:Triglycerides; D000077154:Rosiglitazone