Synthesis and biological activity of l-tyrosine-based PPARγ agonists with reduced molecular weight

Bioorganic & Medicinal Chemistry Letters
2001.0

Abstract

A series of PPARgamma agonists were synthesized from L-tyrosine that incorporated low molecular weight N-substituents. The most potent analogue, pyrrole (4e), demonstrated a K(i) of 6.9nM and an EC(50) of 4.7nM in PPARgamma binding and functional assays, respectively. Pyrrole (4e), which is readily synthesized from L-tyrosine methyl ester in four steps, also demonstrated in vivo activity in a rodent model of Type 2 diabetes.

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