Optimization of Activity, Selectivity, and Liability Profiles in 5-Oxopyrrolopyridine DPP4 Inhibitors Leading to Clinical Candidate (Sa)-2-(3-(Aminomethyl)-4-(2, 4- …

P Devasthale, Y Wang, W Wang, J Fevig…

Index: Devasthale, Pratik; Wang, Ying; Wang, Wei; Fevig, John; Feng, Jianxin; Wang, Aiying; Harrity, Tom; Egan, Don; Morgan, Nathan; Cap, Michael; Fura, Aberra; Klei, Herbert E.; Kish, Kevin; Weigelt, Carolyn; Sun, Lucy; Levesque, Paul; Moulin, Frederic; Li, Yi-Xin; Zahler, Robert; Kirby, Mark S.; Hamann, Lawrence G. Journal of Medicinal Chemistry, 2013 , vol. 56, # 18 p. 7343 - 7357

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Citation Number: 9

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.