2. Academic Validation
  3. 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)

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)

  • J Med Chem. 2013 Sep 26;56(18):7343-57. doi: 10.1021/jm4008906.
Pratik Devasthale 1,  Ying Wang,  Wei Wang,  John Fevig,  JianXin Feng,  Aiying Wang,  Tom Harrity,  Don Egan,  Nathan Morgan,  Michael Cap,  Aberra Fura,  Herbert E Klei,  Kevin Kish,  Carolyn Weigelt,  Lucy Sun,  Paul Levesque,  Frederic Moulin,  Yi-Xin Li,  Robert Zahler,  Mark S Kirby,  Lawrence G Hamann
Affiliations

Affiliation

  • 1 Metabolic Diseases Chemistry, ‡Metabolic Diseases Biology, §Pharmaceutical Candidate Optimization, ∥Protein Science and Structure, ⊥Computer-Assisted Drug Design, Bristol-Myers Squibb Research and Development , Princeton, New Jersey 08543-5400, United States.
PMID: 23964740 DOI: 10.1021/jm4008906
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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