1. Phenylalanine derivatives as GPR142 agonists for the treatment of type II diabetes.
- Author
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Du X, Kim YJ, Lai S, Chen X, Lizarzaburu M, Turcotte S, Fu Z, Liu Q, Zhang Y, Motani A, Oda K, Okuyama R, Nara F, Murakoshi M, Fu A, Reagan JD, Fan P, Xiong Y, Shen W, Li L, Houze J, and Medina JC
- Subjects
- Animals, Blood Glucose analysis, Dose-Response Relationship, Drug, Drug Stability, Glucose Tolerance Test, HEK293 Cells, Humans, Hypoglycemic Agents administration & dosage, Hypoglycemic Agents chemistry, Insulin blood, Insulin metabolism, Insulin Secretion, Male, Mice, Mice, Inbred Strains, Microsomes chemistry, Phenylalanine administration & dosage, Phenylalanine chemistry, Rats, Receptors, G-Protein-Coupled metabolism, Structure-Activity Relationship, Diabetes Mellitus, Type 2 drug therapy, Hypoglycemic Agents pharmacology, Phenylalanine pharmacology, Receptors, G-Protein-Coupled agonists
- Abstract
GPR142 is a novel GPCR that is predominantly expressed in pancreatic β-cells. GPR142 agonists potentiate glucose-dependent insulin secretion, and therefore can reduce the risk of hypoglycemia. Optimization of our lead pyridinone-phenylalanine series led to a proof-of-concept compound 22, which showed in vivo efficacy in mice with dose-dependent increase in insulin secretion and a decrease in glucose levels., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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