| Title : (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrr olidin-2-yl]-methanone: a potent, selective, orally active dipeptidyl peptidase IV inhibitor - Ammirati_2009_Bioorg.Med.Chem.Lett_19_1991 |
| Author(s) : Ammirati MJ , Andrews KM , Boyer DD , Brodeur AM , Danley DE , Doran SD , Hulin B , Liu S , McPherson RK , Orena SJ , Parker JC , Polivkova J , Qiu X , Soglia CB , Treadway JL , VanVolkenburg MA , Wilder DC , Piotrowski DW |
| Ref : Bioorganic & Medicinal Chemistry Lett , 19 :1991 , 2009 |
|
Abstract :
A series of 4-substituted proline amides was synthesized and evaluated as inhibitors of dipeptidyl pepdidase IV for the treatment of type 2 diabetes. (3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrr olidin-2-yl]-methanone (5) emerged as a potent (IC(50) = 13 nM) and selective compound, with high oral bioavailability in preclinical species and low plasma protein binding. Compound 5, PF-00734200, was selected for development as a potential new treatment for type 2 diabetes. |
| PubMedSearch : Ammirati_2009_Bioorg.Med.Chem.Lett_19_1991 |
| PubMedID: 19275964 |
| Gene_locus related to this paper: human-DPP4 |
| Inhibitor | Gosogliptin |
| Gene_locus | human-DPP4 |
| Structure | 3F8S |
Ammirati MJ, Andrews KM, Boyer DD, Brodeur AM, Danley DE, Doran SD, Hulin B, Liu S, McPherson RK, Orena SJ, Parker JC, Polivkova J, Qiu X, Soglia CB, Treadway JL, VanVolkenburg MA, Wilder DC, Piotrowski DW (2009)
(3,3-Difluoro-pyrrolidin-1-yl)-[(2S,4S)-(4-(4-pyrimidin-2-yl-piperazin-1-yl)-pyrr olidin-2-yl]-methanone: a potent, selective, orally active dipeptidyl peptidase IV inhibitor
Bioorganic & Medicinal Chemistry Lett
19 :1991
Ammirati MJ, Andrews KM, Boyer DD, Brodeur AM, Danley DE, Doran SD, Hulin B, Liu S, McPherson RK, Orena SJ, Parker JC, Polivkova J, Qiu X, Soglia CB, Treadway JL, VanVolkenburg MA, Wilder DC, Piotrowski DW (2009)
Bioorganic & Medicinal Chemistry Lett
19 :1991