Structure Report for: 3SX4

Wang, W., Devasthale, P., Wang, A., Harrity, T., Egan, D., Morgan, N., Cap, M., Fura, A., Klei, H.E., Kish, K., Weigelt, C., Sun, L., Levesque, P., Li, Y.X., Zahler, R., Kirby, M.S., Hamann, L.G.

Title: 7-Oxopyrrolopyridine-derived DPP4 inhibitors-mitigation of CYP and hERG liabilities via introduction of polar functionalities in the active site
Wang W, Devasthale P, Wang A, Harrity T, Egan D, Morgan N, Cap M, Fura A, Klei HE and Hamann LG <7 more author(s)> Wang W, Devasthale P, Wang A, Harrity T, Egan D, Morgan N, Cap M, Fura A, Klei HE, Kish K, Weigelt C, Sun L, Levesque P, Li YX, Zahler R, Kirby MS, Hamann LG (- 7)
Ref: Bioorganic & Medicinal Chemistry Lett, 21:6646, 2011 : PubMed
Abstract


ESTHER: Wang_2011_Bioorg.Med.Chem.Lett_21_6646
PubMedSearch: Wang 2011 Bioorg.Med.Chem.Lett 21 6646
PubMedID: 21996520
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: CHEMBL1910114, CHEMBL1909991

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 muM, respectively, showed a significant improvement in insulin response after single doses of 3 and 10 mumol/kg in ob/ob mice.