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.
Design, synthesis, and SAR of 7-oxopyrrolopyridine-derived DPP4 inhibitors are described. The preferred stereochemistry of these atropisomeric biaryl analogs has been identified as Sa. Compound (+)-3t, with a K(i) against DPP4, DPP8, and DPP9 of 0.37 nM, 2.2, and 5.7 μM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 μmol/kg in ob/ob mice.
Lucy Sun合作论文数3Pc Levesque合作论文数3Harrity Tom合作论文数3Lawrence G Hamann合作论文数3
Aiying Wang (王爱英)合作论文数Department of Chemistry and Biochemistry, University of South Carolina, Columbia, SC 29208 USA3Robert Zahler合作论文数Bristol-Myers Squibb Pharmaceutical Research Institute3Nathan Morgan合作论文数3Mark S. Kirby合作论文数3Aberra Fura合作论文数3Kevin Kish合作论文数3Pratik Devasthale合作论文数3Wei Wang合作论文数2Yi-Xin Li合作论文数2Carolyn A. Weigelt合作论文数2Michael Cap合作论文数2
Herbert E Klei合作论文数2Jianxin Feng合作论文数1Frederic Moulin合作论文数1Fevig John合作论文数1
Ying Wang合作论文数University of Science and Technology, Beijing,China
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