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JOURNAL ARTICLE
RESEARCH SUPPORT, NON-U.S. GOV'T
Synthesis and biological evaluation of pyrimidine derivatives with diverse azabicyclic ether/amine as novel GPR119 agonist.
Bioorganic & Medicinal Chemistry Letters 2017 June 2
A class of novel pyrimidine derivatives bearing diverse conformationally restricted azabicyclic ether/amine were designed, synthesized and evaluated for their GPR119 agonist activities against type 2 diabetes. Most compounds exhibited superior hEC50 values to endogenous lipid oleoylethanolamide (OEA). Analogs with 2-fluoro substitution in the aryl ring showed more potent GPR119 activation than those without fluorine. Especially compound 27m synthesized from endo-azabicyclic alcohol was observed to have the best EC50 value (1.2nM) and quite good agonistic activity (112.2% max) as a full agonist.
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