Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2,4-dichlorophenyl)-2-methyl-5-oxo-5H-pyrrolo[3,4-b]pyridin-6(7H)-yl)-N,N-dimethylacetamide (BMS-767778)
Journal of Medicinal Chemistry2013Vol. 56(18), pp. 7343–7357
Citations Over TimeTop 16% of 2013 papers
Pratik Devasthale, Ying Wang, Wei Wang, John M. Fevig, Jianxin Feng, Aiying Wang, Tom Harrity, Don Egan, Nathan Morgan, Michael Cap, Aberra Fura, Herbert E. Klei, Kevin Kish, Carolyn A. Weigelt, Lucy Sun, Paul Lévesque, Frederic Moulin, Yixin Li, Robert Zahler, Mark Kirby, Lawrence G. Hamann
Abstract
Optimization of a 5-oxopyrrolopyridine series based upon structure-activity relationships (SARs) developed from our previous efforts on a number of related bicyclic series yielded compound 2s (BMS-767778) with an overall activity, selectivity, efficacy, PK, and developability profile suitable for progression into the clinic. SAR in the series and characterization of 2s are described.
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