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ID: ALA1770133
Journal: Bioorg Med Chem Lett
Title: Design of potent and selective GPR119 agonists for type II diabetes.
Authors: Szewczyk JW, Acton J, Adams AD, Chicchi G, Freeman S, Howard AD, Huang Y, Li C, Meinke PT, Mosely R, Murphy E, Samuel R, Santini C, Yang M, Zhang Y, Zhao K, Wood HB.
Abstract: Screening of the Merck sample collection identified compound 1 as a weakly potent GPR119 agonist (hEC(50)=3600 nM). Dual termini optimization of 1 led to compound 36 having improved potency, selectivity, and formulation profile, however, modest physical properties (PP) hindered its utility. Design of a new core containing a cyclopropyl restriction yielded further PP improvements and when combined with the termini SAR optimizations yielded a potent and highly selective agonist suitable for further preclinical development (58).
CiteXplore: 21273063