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

Article abstract of DOI:10.1016/S0960-894X(01)00649-7

A series of PPARγ agonists were synthesized from L-tyrosine that incorporated low molecular weight N-substituents. The most potent analogue, pyrrole (4e), demonstrated a K_i of 6.9 nM and an EC₅₀ of 4.7 nM in PPARγ 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.