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

…, MA Hashim, EA Hull-Ryde, I Kaldor…

Index: Henke, Brad R.; Blanchard, Steven G.; Brackeen, Marcus F.; Brown, Kathleen K.; Cobb, Jeff E.; Collins, Jon L.; Harrington Jr., W. Wallace; Hashim, Mir A.; Hull-Ryde, Emily A.; Kaldor, Istvan; Kliewer, Steven A.; Lake, Debra H.; Leesnitzer, Lisa M.; Lehmann, Juergen M.; Lenhard, James M.; Orband-Miller, Lisa A.; Miller, John F.; Mook Jr., Robert A.; Noble, Stewart A.; Oliver Jr., William; Parks, Derek J.; Plunket, Kelli D.; Szewczyk, Jerzy R.; Willson, Timothy M. Journal of Medicinal Chemistry, 1998 , vol. 41, # 25 p. 5020 - 5036

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Citation Number: 345

Abstract

We have identified a novel series of antidiabetic N-(2-benzoylphenyl)-l-tyrosine derivatives which are potent, selective PPARγ agonists. Through the use of in vitro PPARγ binding and functional assays (2 S)-3-(4-(benzyloxy) phenyl)-2-((1-methyl-3-oxo-3-phenylpropenyl) amino) propionic acid (2) was identified as a structurally novel PPARγ agonist. Structure- activity relationships identified the 2-aminobenzophenone moiety as a suitable isostere for ...