(trifluoromethyl)pyrimidine (BETP), a Small Molecule Positive Allosteric Modulator of the Glucagon-Like Peptide-1 (GLP-1) Receptor
نویسندگان
چکیده
Pharmacokinetics, Dynamics and Metabolism–New Chemical Entities, Groton, CT (H.E., R.S., T.S.M.) and Cambridge, MA (A.S.K.) Cardiovascular, Metabolic and Endocrine Diseases Medicinal Chemistry, Cambridge, MA (D.J.E., B.D.S., D.A.G., W.M.N., D.A.P.) and Groton (C.L.) Cardiovascular, Metabolic and Endocrine Diseases Research Unit, Cambridge, MA (J.P.F., X.L., M.J.) Pfizer, Inc. DMD Fast Forward. Published on May 7, 2013 as doi:10.1124/dmd.113.052183
منابع مشابه
Small molecule allosteric modulation of the glucagon-like Peptide-1 receptor enhances the insulinotropic effect of oxyntomodulin.
Identifying novel mechanisms to enhance glucagon-like peptide-1 (GLP-1) receptor signaling may enable nascent medicinal chemistry strategies with the aim of developing new orally available therapeutic agents for the treatment of type 2 diabetes mellitus. Therefore, we tested the hypothesis that selectively modulating the low-affinity GLP-1 receptor agonist, oxyntomodulin, would improve the insu...
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4-(3-(Benzyloxy)phenyl)-2-(ethylsulfinyl)-6-(trifluoromethyl)pyrimidine (BETP) represents a novel small-molecule activator of the glucagonlike peptide-1 receptor (GLP-1R), and exhibits glucose-dependent insulin secretion in rats following i.v. (but not oral) administration. To explore the quantitative pharmacology associated with GLP-1R agonism in preclinical species, the in vivo pharmacokineti...
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The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small molecule GLP-1 receptor agonists. Although the GLP-1 receptor is a member of the structurally complex class B1 family of GPCRs, in recent years, a diverse array of orthosteric and allosteric n...
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