| Title : (3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)- 1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes - Biftu_2007_Bioorg.Med.Chem.Lett_17_49 |
| Author(s) : Biftu T , Feng D , Qian X , Liang GB , Kieczykowski G , Eiermann G , He H , Leiting B , Lyons K , Petrov A , Sinha-Roy R , Zhang B , Scapin G , Patel S , Gao YD , Singh S , Wu J , Zhang X , Thornberry NA , Weber AE |
| Ref : Bioorganic & Medicinal Chemistry Lett , 17 :49 , 2007 |
|
Abstract :
Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin. |
| PubMedSearch : Biftu_2007_Bioorg.Med.Chem.Lett_17_49 |
| PubMedID: 17055272 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | Diazepanone-Analog-18 Diazepanone-Analog-1 |
| Gene_locus | human-DPP4 |
| Structure | 2IIV 2IIT |
Biftu T, Feng D, Qian X, Liang GB, Kieczykowski G, Eiermann G, He H, Leiting B, Lyons K, Petrov A, Sinha-Roy R, Zhang B, Scapin G, Patel S, Gao YD, Singh S, Wu J, Zhang X, Thornberry NA, Weber AE (2007)
(3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)- 1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes
Bioorganic & Medicinal Chemistry Lett
17 :49
Biftu T, Feng D, Qian X, Liang GB, Kieczykowski G, Eiermann G, He H, Leiting B, Lyons K, Petrov A, Sinha-Roy R, Zhang B, Scapin G, Patel S, Gao YD, Singh S, Wu J, Zhang X, Thornberry NA, Weber AE (2007)
Bioorganic & Medicinal Chemistry Lett
17 :49