Duffy_2007_Bioorg.Med.Chem.Lett_17_2879

Reference

Title : 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV - Duffy_2007_Bioorg.Med.Chem.Lett_17_2879
Author(s) : Duffy JL , Kirk BA , Wang L , Eiermann GJ , He H , Leiting B , Lyons KA , Patel RA , Patel SB , Petrov A , Scapin G , Wu JK , Thornberry NA , Weber AE
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :2879 , 2007
Abstract :

A novel series of 4-aminophenylalanine and 4-aminocyclohexylalanine derivatives were designed and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4). The phenylalanine series afforded compounds such as 10 that were potent and selective (DPP-4, IC(50)=28nM), but exhibited limited oral bioavailability. The corresponding cyclohexylalanine derivatives such as 25 afforded improved PK exposure and efficacy in a murine OGTT experiment. The X-ray crystal structure of 25 bound to the DPP-4 active site is presented.

PubMedSearch : Duffy_2007_Bioorg.Med.Chem.Lett_17_2879
PubMedID: 17350841
Gene_locus related to this paper: human-DPP4

Related information

Inhibitor 4-aminocyclohexylalanine-derivative-25
Gene_locus human-DPP4
Structure 2OPH

Citations formats

Duffy JL, Kirk BA, Wang L, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE (2007)
4-aminophenylalanine and 4-aminocyclohexylalanine derivatives as potent, selective, and orally bioavailable inhibitors of dipeptidyl peptidase IV
Bioorganic & Medicinal Chemistry Lett 17 :2879

Duffy JL, Kirk BA, Wang L, Eiermann GJ, He H, Leiting B, Lyons KA, Patel RA, Patel SB, Petrov A, Scapin G, Wu JK, Thornberry NA, Weber AE (2007)
Bioorganic & Medicinal Chemistry Lett 17 :2879