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5-aryl thiazolidine-2,4-diones: discovery of PPAR dual alpha/gamma agonists as antidiabetic agents |
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| Authors: | Desai Ranjit C Han Wei Metzger Edward J Bergman Jeffrey P Gratale Dominick F MacNaul Karen L Berger Joel P Doebber Thomas W Leung Kwan Moller David E Heck James V Sahoo Soumya P |
| Institution: | Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000, Rahway, NJ 07065-0900, USA. ranjit_desai@merck.com |
| 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. |
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