(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.

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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

(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.

Bioorg Med Chem Lett. 2009 Apr 1;19(7):1991-5. doi: 10.1016/j.bmcl.2009.02.041. Epub 2009 Feb 13.

PubMed ID
19275964 [ View in PubMed
]
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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
GosogliptinDipeptidyl peptidase 4IC 50 (nM)12.9N/AN/ADetails
GosogliptinDipeptidyl peptidase 4IC 50 (nM)11.3N/AN/ADetails