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

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Liu KG, Lambert MH, Ayscue AH, Henke BR, Leesnitzer LM, Oliver WR Jr, Plunket KD, Xu HE, Sternbach DD, Willson TM

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

Bioorg Med Chem Lett. 2001 Dec 17;11(24):3111-3.

PubMed ID
11720854 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
PioglitazonePeroxisome proliferator-activated receptor gammaEC 50 (nM)580N/AN/ADetails
PioglitazonePeroxisome proliferator-activated receptor gammaKi (nM)630N/AN/ADetails
RosiglitazonePeroxisome proliferator-activated receptor gammaEC 50 (nM)43N/AN/ADetails
RosiglitazonePeroxisome proliferator-activated receptor gammaKi (nM)120N/AN/ADetails