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(2R)-2-methylchromane-2-carboxylic acids: discovery of selective PPARalpha agonists as hypolipidemic agents. 2005
Hiroo Koyama, and
Julia K Boueres, and
Daniel J Miller, and
Joel P Berger, and
Karen L MacNaul, and
Pei-ran Wang, and
Marc C Ippolito, and
Samuel D Wright, and
Arun K Agrawal, and
David E Moller, and
Soumya P Sahoo
Department of Medicinal Chemistry, Merck Research Laboratories, PO Box 2000 Rahway, NJ 07065, USA. hiroo_koyama@merck.com
A SAR study was conducted on chromane-2-carboxylic acid toward selective PPARalpha agonisim. As a result, highly potent, and selective PPARalpha agonists were discovered. The optimized compound 43 exhibited robust lowering of total cholesterol levels in hamster and dog animal models.
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