Synthesis and structure-activity relationships of 2-aryl-4-oxazolylmethoxy benzylglycines and 2-aryl-4-thiazolylmethoxy benzylglycines as novel, potent PPARalpha selective activators- PPARalpha and PPARgamma selectivity modulation.

A series of potent, selective PPARα modulators incorporating 2-aryl-4-oxazolylmethoxy and 2-aryl-4-thiazolylmethoxy into oxybenzylglycine framework were designed and synthesized (structure shown as 2). The optimizations of R1, R2, and R3 in 2 have led to the identification of several potent, selective PPARα modulators such as 2a, 2l, and 2s. Their PK, in vivo pharmacology, and ADME profiles are discussed.