TRIFLUOROMETHYL PYRIMIDINE: SYNTHESIS AND ANTIDIABETIC EVALUATION OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS
Shaikha S. AlNeyadi, Abdu Adem, Naheed Amer, and Ibrahim M. Abdou
ABSTRACT
In this study, two series of new trisubstituted pyrimidine derivatives were designed and synthesized using an efficient route, and these derivatives were evaluated for GLP-1 receptor agonist activity. In the first series, new pyrimidines substituted at positions 2 with a p-fluorobenzoyl moiety was synthesized in a good yield. In the second series, the designed pyrimidine templates were substituted at positions 2 with different cycloaliphatic amines, and these compounds were successfully produced with yields of 77-89%. In vitro experiments in cultured cells showed that compounds 4a and 6a (10-15 to 10-9 M) significantly increased insulin secretion compared to the control cells in the absence and presence of 2.8 mM glucose. Compounds 4b and 6d demonstrated significance in the absence of glucose. These results suggest a valuable starting point for the design and discovery of orally active GLP-1 receptor agonists.
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