Identification of a series of PPARγ/δ dual agonists via solid-Phase parallel synthesis

We have developed a general solid-phase synthesis for identification of PPAR ligands. Synthesis of a 480-member library led to the identification of a potent PPARγ/δ dual agonist 23. Compound 23 showed good plasma exposure in rats and demonstrated antihyperglycemic and antihyperlipidemic efficacy in...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2001-11, Vol.11 (22), p.2959-2962
Hauptverfasser:	Liu, Kevin G, Lambert, Millard H, Leesnitzer, Lisa M, Oliver, William, Ott, Ronda J, Plunket, Kelli D, Stuart, Ludwig W, Brown, Peter J, Willson, Timothy M, Sternbach, Daniel D
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Diabetes Mellitus - therapy DNA-Binding Proteins - agonists Enzyme Activators - chemical synthesis Enzyme Activators - pharmacology General and cellular metabolism. Vitamins Hyperglycemia - prevention & control Hyperlipidemias - prevention & control Ligands Medical sciences Pharmacology. Drug treatments Rats Rats, Zucker Receptors, Cytoplasmic and Nuclear - agonists Transcription Factors - agonists
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Zusammenfassung:	We have developed a general solid-phase synthesis for identification of PPAR ligands. Synthesis of a 480-member library led to the identification of a potent PPARγ/δ dual agonist 23. Compound 23 showed good plasma exposure in rats and demonstrated antihyperglycemic and antihyperlipidemic efficacy in diabetic fatty Zucker rats. A potent PPARγ/δ dual agonist was identified from a 480-member library. This compound showed good plasma stability in rats and antihyperglycemic and antihyperlipidemic efficacy in a rodent model.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/S0960-894X(01)00596-0