Referenced in: none

Automatically associated channels: Kv11.1

Title: 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site.

Authors: Wei Wang, Pratik Devasthale, Aiying Wang, Tom Harrity, Don Egan, Nathan Morgan, Michael Cap, Aberra Fura, Herbert E Klei, Kevin Kish, Carolyn Weigelt, Lucy Sun, Paul Levesque, Yi-Xin Li, Robert Zahler, Mark S Kirby, Lawrence G Hamann

Journal, date & volume: Bioorg. Med. Chem. Lett., 2011 Nov 15 , 21, 6646-51

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/21996520

Abstract
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.