Biftu_2007_Bioorg.Med.Chem.Lett_17_3384

Reference

Title : Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin - Biftu_2007_Bioorg.Med.Chem.Lett_17_3384
Author(s) : Biftu T , Scapin G , Singh S , Feng D , Becker JW , Eiermann G , He H , Lyons K , Patel S , Petrov A , Sinha-Roy R , Zhang B , Wu J , Zhang X , Doss GA , Thornberry NA , Weber AE
Ref : Bioorganic & Medicinal Chemistry Lett , 17 :3384 , 2007
Abstract :

Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC(50)=21 nM) with excellent in vivo activity and pharmacokinetic profile.

PubMedSearch : Biftu_2007_Bioorg.Med.Chem.Lett_17_3384
PubMedID: 17433672
Gene_locus related to this paper: human-DPP4

Related information

Inhibitor CHEMBL233360    Sitagliptin
Gene_locus human-DPP4
Structure 2P8S

Citations formats

Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE (2007)
Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin
Bioorganic & Medicinal Chemistry Lett 17 :3384

Biftu T, Scapin G, Singh S, Feng D, Becker JW, Eiermann G, He H, Lyons K, Patel S, Petrov A, Sinha-Roy R, Zhang B, Wu J, Zhang X, Doss GA, Thornberry NA, Weber AE (2007)
Bioorganic & Medicinal Chemistry Lett 17 :3384