Structure Report for: 2QT9

Kaelin, D.E., Smetin, A.L, Eiermann, G.J., He, H., Leiting, B., Lyons, K.A., Patel, R.A, Patel, S.B, Petrov, A., Scapin, G., Wu, J.K., Thornberry, N.A, Weber, A.E, Duffy, J.L.

Title: 4-arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV
Kaelin DE, Smenton AL, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A and Duffy JL <4 more author(s)> Kaelin DE, Smenton AL, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE, Duffy JL (- 4)
Ref: Bioorganic & Medicinal Chemistry Lett, 17:5806, 2007 : PubMed
Abstract


ESTHER: Kaelin_2007_Bioorg.Med.Chem.Lett_17_5806
PubMedSearch: Kaelin 2007 Bioorg.Med.Chem.Lett 17 5806
PubMedID: 17851076
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: 4-aryl-cyclohexylalanine-inhibitor-1, 4-aryl-cyclohexylalanine-inhibitor-2

Abstract

A novel series of 4-arylcyclohexylalanine DPP-4 inhibitors was synthesized and tested for inhibitory activity as well as selectivity over the related proline-specific enzymes DPP-8 and DPP-9. Optimization of this series led to 28 (DPP-4 IC(50)=4.8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated that this compound effectively reduced glucose excursion in lean mice.