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

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. doi: 10.1016/s0960-894x(01)00649-7.
K G Liu 1,  M H Lambert,  A H Ayscue,  B R Henke,  L M Leesnitzer,  W R Oliver Jr,  K D Plunket,  H E Xu,  D D Sternbach,  T M Willson
Affiliations

Affiliation

  • 1 Nuclear Receptor Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. kliu@kalypsys.com
PMID: 11720854 DOI: 10.1016/s0960-894x(01)00649-7
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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