Synthesis and biological evaluation of thienopyrimidine derivatives as GPR119 agonists |
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| Affiliation: | 1. Department of Endocrinology, Clinical Medical College, Yangzhou University, Yangzhou 225001, China;2. Institute of Combined Chinese and Western Medicine, Medical College, Yangzhou University, Yangzhou 225001, China;3. Department of Physiology, Nanjing University of Chinese Medicine Hanlin College, Taizhou 225300, China |
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| Abstract: | A series of thienopyrimidine derivatives was synthesized and evaluated for their GPR119 agonistic ability. Several thienopyrimidine derivatives containing R1 and R2 substituents displayed potent GPR119 agonistic activity. Among them, compound 5d, which is a prototype, showed good in vitro activity with an EC50 value of 3 nM and human and rat liver microsomal stability. Compound 5d exhibited no CYP inhibition and induction, Herg binding, or mutagenic potential. Compound 5d showed increase insulin secretion in beta TC-6 cell and lowered the glucose excursion in mice in an oral glucose-tolerance test. |
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| Keywords: | Diabetes Thienopyrimidine GPR119 Treatment |
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