(2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-p yrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV.

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Yeh TK, Tsai TY, Hsu T, Cheng JH, Chen X, Song JS, Shy HS, Chiou MC, Chien CH, Tseng YJ, Huang CY, Yeh KC, Huang YL, Huang CH, Huang YW, Wang MH, Tang HK, Chao YS, Chen CT, Jiaang WT

(2S,4S)-1-[2-(1,1-dimethyl-3-oxo-3-pyrrolidin-1-yl-propylamino)acetyl]-4-fluoro-p yrrolidine-2-carbonitrile: a potent, selective, and orally bioavailable dipeptide-derived inhibitor of dipeptidyl peptidase IV.

Bioorg Med Chem Lett. 2010 Jun 15;20(12):3596-600. doi: 10.1016/j.bmcl.2010.04.124. Epub 2010 May 17.

PubMed ID
20483603 [ View in PubMed
]
Abstract

A series of 2-[3-[2-[(2S)-2-cyano-1-pyrrolidinyl]-2-oxoethylamino]-3-methyl-1-oxobutyl]-based DPP-IV inhibitors with various monocyclic amines were synthesized. The structure-activity relationships (SAR) led to the discovery of potent DPP-IV inhibitors, having IC(50) values of <100 nM with excellent selectivity over the closely related enzymes, DPP-II, DPP8, DPP9 and FAP (IC(50)>20 microM). Of these compounds, the analogues 12a, 12h and 12i exhibited a long-lasting ex vivo DPP-IV inhibition in rats.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
SaxagliptinDipeptidyl peptidase 4IC 50 (nM)3.4N/AN/ADetails
SitagliptinDipeptidyl peptidase 4IC 50 (nM)18N/AN/ADetails
SitagliptinDipeptidyl peptidase 4IC 50 (nM)30N/AN/ADetails
SitagliptinDipeptidyl peptidase 4IC 50 (nM)46N/AN/ADetails
VildagliptinDipeptidyl peptidase 4IC 50 (nM)51N/AN/ADetails
VildagliptinDipeptidyl peptidase 4IC 50 (nM)17N/AN/ADetails
VildagliptinDipeptidyl peptidase 4IC 50 (nM)16N/AN/ADetails