N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.

@article{Henke1998N2BenzoylphenylLtyrosinePA,
  title={N-(2-Benzoylphenyl)-L-tyrosine PPARgamma agonists. 1. Discovery of a novel series of potent antihyperglycemic and antihyperlipidemic agents.},
  author={Brad R Henke and Steven G. Blanchard and Marcus F. Brackeen and Kimberly K Brown and Jeff E Cobb and Jon L. Collins and W. Wallace Harrington and Mir A. Hashim and Emily A. Hull-Ryde and Istvan W Kaldor and Steven A. Kliewer and D H Lake and Lisa M. Leesnitzer and J{\"u}rgen M. Lehmann and James M. Lenhard and Lisa A. Orband-Miller and John F Miller and Robert A. Mook and Stewart A. Noble and Walter Oliver and Derek J. Parks and Kelli D. Plunket and Jerzy R Szewczyk and Timothy M Willson},
  journal={Journal of medicinal chemistry},
  year={1998},
  volume={41 25},
  pages={5020-36}
}
We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-L-tyrosine derivatives which are potent, selective PPARgamma agonists. Through the use of in vitro PPARgamma binding and functional assays (2S)-3-(4-(benzyloxy)phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl)+ ++amin o)propionic acid (2) was identified as a structurally novel PPARgamma agonist. Structure-activity relationships identified the 2-aminobenzophenone moiety as a suitable isostere for the chemically labile enaminone… CONTINUE READING