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.
Bioorganic & Medicinal Chemistry Letters(2010)
Abstract
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.
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Key words
PPARα,PPARγ,Activator,Structure–activity relationship,Selectivity modulation
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