title: 5-aryl thiazolidine-2,4-diones: discovery of PPAR dual alpha/gamma agonists as antidiabetic agents.
abstract: A novel series of 5-aryl thiazolidine-2,4-diones based dual PPARalpha/gamma agonists was identified. A number of highly potent and orally bioavailable analogues were synthesized. Efficacy study results of some of these analogues in the db/db mice model of type 2 diabetes showed them superior to rosiglitazone in correcting hyperglycemia and hypertriglyceridemia.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. ranjit_desai@merck.com
authors.forename: Ranjit C
authors.initials: RC
authors.lastname: Desai
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Metzger
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Bergman
authors.forename: Dominick F
authors.initials: DF
authors.lastname: Gratale
authors.forename: Karen L
authors.initials: KL
authors.lastname: MacNaul
authors.forename: Joel P
authors.initials: JP
authors.lastname: Berger
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Doebber
authors.forename: Kwan
authors.initials: K
authors.lastname: Leung
authors.forename: David E
authors.initials: DE
authors.lastname: Moller
authors.forename: James V
authors.initials: JV
authors.lastname: Heck
authors.forename: Soumya P
authors.initials: SP
authors.lastname: Sahoo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D004195:Disease Models, Animal; D006943:Hyperglycemia / Q000188:drug therapy; D015228:Hypertriglyceridemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D051379:Mice; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000378:metabolism; D000077154:Rosiglitazone; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis* / Q000494:pharmacology; D014157:Transcription Factors / Q000819:agonists* / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone