Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1374337 | Bioorganic & Medicinal Chemistry Letters | 2011 | 5 Pages |
Abstract
Screening of the Merck sample collection identified compound 1 as a weakly potent GPR119 agonist (hEC50 = 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).
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Jason W. Szewczyk, John Acton, Alan D. Adams, Gary Chicchi, Stanley Freeman, Andrew D. Howard, Yong Huang, Cai Li, Peter T. Meinke, Ralph Mosely, Elizabeth Murphy, Rachel Samuel, Conrad Santini, Meng Yang, Yong Zhang, Kake Zhao, Harold B. Wood,