Modeling assisted rational design of novel, potent, and selective pyrrolopyrimidine DPP-4 inhibitors.
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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
Drug Target Property Measurement pH Temperature (°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)CYCLOHEXANAMINE Dipeptidyl peptidase 4 IC 50 (nM) 21 N/A N/A Details Sitagliptin Dipeptidyl peptidase 4 IC 50 (nM) 18 N/A N/A Details