Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors.

Article Details

Citation

Gao YD, Feng D, Sheridan RP, Scapin G, Patel SB, Wu JK, Zhang X, Sinha-Roy R, Thornberry NA, Weber AE, Biftu T

Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors.

Bioorg Med Chem Lett. 2007 Jul 15;17(14):3877-9. Epub 2007 May 3.

PubMed ID
17502141 [ View in PubMed
]
Abstract

Molecular modeling was used to improve potency of the cyclohexylamine series. In addition, a 3-D QSAR method was used to gain insight for reducing off-target DPP-8/9 activities. Compounds 3, 4, and 5 were synthesized and found to be potent DPP-4 inhibitors, in particular 4 and 5 are designed to be highly selective against off-target DASH enzymes while maintaining potency on DPP-4.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(1S,2R,5S)-5-[3-(TRIFLUOROMETHYL)-5,6-DIHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRAZIN-7(8H)-YL]-2-(2,4,5-TRIFLUOROPHENYL)CYCLOHEXANAMINEDipeptidyl peptidase 4IC 50 (nM)21N/AN/ADetails
SitagliptinDipeptidyl peptidase 4IC 50 (nM)18N/AN/ADetails