2. Academic Validation
  3. Amphipathic 3-phenyl-7-propylbenzisoxazoles; human pPaR gamma, delta and alpha agonists

Amphipathic 3-phenyl-7-propylbenzisoxazoles; human pPaR gamma, delta and alpha agonists

  • Bioorg Med Chem Lett. 2003 Mar 10;13(5):931-5. doi: 10.1016/s0960-894x(02)01029-6.
Alan D Adams 1,  Winston Yuen,  Zao Hu,  Conrad Santini,  A Brian Jones,  Karen L MacNaul,  Joel P Berger,  Thomas W Doebber,  David E Moller
Affiliations

Affiliation

  • 1 Departments of Basic Chemistry, Merck Research Laboratories, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065, USA. [email protected]
PMID: 12617924 DOI: 10.1016/s0960-894x(02)01029-6
Abstract

A series of amphipathic 3-phenylbenzisoxazoles were found to be potent agonists of human PPARalpha, gamma and delta. The optimization of acid proximal structure for in vitro and in vivo potency is described. Results of po dosed efficacy studies in the db/db mouse model of type 2 diabetes showed efficacy equal or superior to Rosiglitazone in correcting hyperglycemia and hypertriglyceridemia. Good functional receptor selectivity for PPARalpha and gamma over PPARdelta can be obtained.

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