5-aryl thiazolidine-2,4-diones: discovery of PPAR dual alpha/gamma agonists as antidiabetic agents.
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.
Desai
Ranjit C
RC
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. ranjit_desai@merck.com
Han
Wei
W
Metzger
Edward J
EJ
Bergman
Jeffrey P
JP
Gratale
Dominick F
DF
MacNaul
Karen L
KL
Berger
Joel P
JP
Doebber
Thomas W
TW
Leung
Kwan
K
Moller
David E
DE
Heck
James V
JV
Sahoo
Soumya P
SP
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
D007004:Hypoglycemic Agents; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone