Diprolyl nitriles as potent dipeptidyl peptidase IV inhibitors |
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Authors: | Zhao Guohua Taunk Prakash C Magnin David R Simpkins Ligaya M Robl Jeffrey A Wang Aiying Robertson James G Marcinkeviciene Jovita Sitkoff Doree F Parker Rex A Kirby Mark S Hamann Lawrence G |
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Affiliation: | Department of Discovery Chemistry, Bristol-Myers Squibb, Pharmaceutical Research Institute, P.O. Box 5400, Princeton, NJ 08543-5400, USA. guohua.zhao@bms.com |
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Abstract: | Dipeptidyl peptidase IV (DPP4) is a multifunctional type II transmembrane serine peptidase which regulates various physiological processes, most notably plasma glucose homeostasis by cleaving peptide hormones glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Inhibition of DPP4 is a potentially valuable therapy for type 2 diabetes. Synthesis and structure-activity relationships of a series of substituted diprolyl nitriles are described, leading to the identification of compound 1 with a measured DPP4 K(i) of 3.6 nM. |
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