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Author Report for: Stafford JA

Title: Structure-based design of pyridopyrimidinediones as dipeptidyl peptidase IV inhibitors
Lam B, Zhang Z, Stafford JA, Skene RJ, Shi L, Gwaltney SL, 2nd
Ref: Bioorganic & Medicinal Chemistry Lett, 22:6628, 2012 : PubMed
Abstract


ESTHER: Lam_2012_Bioorg.Med.Chem.Lett_22_6628
PubMedSearch: Lam 2012 Bioorg.Med.Chem.Lett 22 6628
PubMedID: 23025999
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: CHEMBL2159182

Abstract

Dipeptidyl peptidase IV (DPP-4) inhibitors have been shown to enhance GLP-1 levels and thereby improve hyperglycemia in type II diabetes. From a small fragment hit, using structure-based design, we have discovered a new class of non-covalent, potent and selective DPP-4 inhibitors.



        

Title: Design and synthesis of pyrimidinone and pyrimidinedione inhibitors of dipeptidyl peptidase IV
Zhang Z, Wallace MB, Feng J, Stafford JA, Skene RJ, Shi L, Lee B, Aertgeerts K, Jennings A and Gwaltney SL <5 more author(s)> Zhang Z, Wallace MB, Feng J, Stafford JA, Skene RJ, Shi L, Lee B, Aertgeerts K, Jennings A, Xu R, Kassel DB, Kaldor SW, Navre M, Webb DR, Gwaltney SL (- 5)
Ref: Journal of Medicinal Chemistry, 54:510, 2011 : PubMed
Abstract


ESTHER: Zhang_2011_J.Med.Chem_54_510
PubMedSearch: Zhang 2011 J.Med.Chem 54 510
PubMedID: 21186796
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: Pyrimidinone-inhibitor1, Pyrimidinone-inhibitor3, Xanthine-inhibitor-4, CHEMBL2159182, Alogliptin

Abstract

The discovery of two classes of heterocyclic dipeptidyl peptidase IV (DPP-4) inhibitors, pyrimidinones and pyrimidinediones, is described. After a single oral dose, these potent, selective, and noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and lowering of blood glucose in animal models of diabetes. Compounds 13a, 27b, and 27j were selected for development.



        

Title: Discovery of alogliptin: a potent, selective, bioavailable, and efficacious inhibitor of dipeptidyl peptidase IV
Feng J, Zhang Z, Wallace MB, Stafford JA, Kaldor SW, Kassel DB, Navre M, Shi L, Skene RJ and Gwaltney SL, 2nd <4 more author(s)> Feng J, Zhang Z, Wallace MB, Stafford JA, Kaldor SW, Kassel DB, Navre M, Shi L, Skene RJ, Asakawa T, Takeuchi K, Xu R, Webb DR, Gwaltney SL, 2nd (- 4)
Ref: Journal of Medicinal Chemistry, 50:2297, 2007 : PubMed
Abstract


ESTHER: Feng_2007_J.Med.Chem_50_2297
PubMedSearch: Feng 2007 J.Med.Chem 50 2297
PubMedID: 17441705
Gene_locus related to this paper: human-DPP4
Inhibitor(s) related to this paper: Alogliptin

Abstract

Alogliptin is a potent, selective inhibitor of the serine protease dipeptidyl peptidase IV (DPP-4). Herein, we describe the structure-based design and optimization of alogliptin and related quinazolinone-based DPP-4 inhibitors. Following an oral dose, these noncovalent inhibitors provide sustained reduction of plasma DPP-4 activity and a lowering of blood glucose in animal models of diabetes. Alogliptin is currently undergoing phase III trials in patients with type 2 diabetes.