Structure Report for: 2RIP

Corbett, J.W., Dirico, K., Song, W., Boscoe, B.P., Doran, S.D., Boyer, D., Qiu, X., Ammirati, M., Vanvolkenburg, M.A., McPherson, R.K., Parker, J.C., Cox, E.D.

Title: Design and synthesis of potent amido- and benzyl-substituted cis-3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl DPP-IV inhibitors
Corbett JW, Dirico K, Song W, Boscoe BP, Doran SD, Boyer D, Qiu X, Ammirati M, VanVolkenburg MA and Cox ED <2 more author(s)> Corbett JW, Dirico K, Song W, Boscoe BP, Doran SD, Boyer D, Qiu X, Ammirati M, VanVolkenburg MA, McPherson RK, Parker JC, Cox ED (- 2)
Ref: Bioorganic & Medicinal Chemistry Lett, 17:6707, 2007 : PubMed
Abstract


ESTHER: Corbett_2007_Bioorg.Med.Chem.Lett_17_6707
PubMedSearch: Corbett 2007 Bioorg.Med.Chem.Lett 17 6707
PubMedID: 17977724
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: cis-3-amino-4-(2-cyanopyrrolidide)pyrrolidinyl-34Q

Abstract

The cis-3-amino-4-(2-cyanopyrrolidide)-pyrrolidine template has been shown to afford low nanomolar inhibitors of human DPP-IV that exhibit a robust PK/PD profile. An X-ray co-crystal structure of 5 confirmed the proposed mode of binding. The potent single digit DPP-IV inhibitor 53 exhibited a preferred PK/PD profile in preclinical animal models and was selected for additional profiling.