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Published on: November 15, 2013
Design, synthesis, and effects of novel phenylpyrimidines as glucagon receptor antagonists
Hojung Choi1, Chang-Yong Lee2, Eun-Young Park3
1Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Yeonsu-gu, Incheon 21999, Republic of Korea; College of Pharmacy, Gachon Institute of Pharmaceutical Science, Gachon University, Yeonsu-gu, Incheon 21936, Republic of Korea.
Abstract:
The hormone glucagon increases blood glucose levels through increasing hepatic glucose output. In diabetic patients, dysregulation of glucagon secretion contributes to hyperglycemia. Thus, the inhibition of glucagon receptor is one target for the treatment of hyperglycemia in type 2 diabetes. Here we designed and synthesized a series of small molecules based on phenylpyrimidine. Of these, the compound (R)-7a most significantly decreased the glucagon-induced cAMP production and glucagon-induced glucose production during in vitro and in vivo assays. In addition, (R)-7a showed good efficacy in glucagon challenge tests and lowered blood glucose levels in diabetic db/db mice. Our results suggest that the compound (R)-7a could be a potential glucose-lowering agent for treating type 2 diabetes.
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