2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra hydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR-12727): a potent, orally active dipeptidyl peptidase IV inhibitor without mechanism-based inactivation of CYP3A.

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Nishio Y, Kimura H, Sawada N, Sugaru E, Horiguchi M, Ono M, Furuta Y, Sakai M, Masui Y, Otani M, Hashizuka T, Honda Y, Deguchi J, Nakagawa T, Nakahira H

2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra hydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR-12727): a potent, orally active dipeptidyl peptidase IV inhibitor without mechanism-based inactivation of CYP3A.

Bioorg Med Chem. 2011 Sep 15;19(18):5490-9. doi: 10.1016/j.bmc.2011.07.042. Epub 2011 Aug 4.

PubMed ID
21865048 [ View in PubMed
]
Abstract

We report on the identification of 2-({6-[(3R)-3-amino-3-methylpiperidine-1-yl]-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetra hydro-5H-pyrrolo[3,2-d]pyrimidine-5-yl}methyl)-4-fluorobenzonitrile (DSR-12727) (7a) as a potent and orally active DPP-4 inhibitor without mechanism-based inactivation of CYP3A. Compound 7a showed good DPP-4 inhibitory activity (IC(50)=1.1 nM), excellent selectivity against related peptidases and other off-targets, good pharmacokinetic and pharmacodynamic profile, great in vivo efficacy in Zucker-fatty rat, and no safety concerns both in vitro and in vivo.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
AlogliptinDipeptidyl peptidase 4IC 50 (nM)1N/AN/ADetails
SitagliptinDipeptidyl peptidase 4IC 50 (nM)3.5N/AN/ADetails
VildagliptinDipeptidyl peptidase 4IC 50 (nM)0.58N/AN/ADetails