| Autor: |
Seth, P. P., Miyaji, A., Jefferson, E. A., Sannes-Lowery, K. A., Osgood, S. A., Propp, S. S., Ranken, R., Massire, C., Sampath, R., Ecker, D. J., Swayze, E. E., Griffey, R. H. |
| Zdroj: |
Journal of Medicinal Chemistry; November 2005, Vol. 48 Issue: 23 p7099-7102, 4p |
| Abstrakt: |
A new class of small molecules that bind the HCV RNA IRES IIA subdomain with sub-micromolar affinity is reported. The benzimidazole hit' 1 with a KD ~100 μM to a 29-mer RNA model of Domain IIA was identified from a 180000-member library using mass spectrometry-based screening methods. Further MS-assisted SAR (structure−activity relationships) studies afforded benzimidazole derivatives with sub-micromolar binding affinity for the IIA RNA construct. The optimized benzimidazoles demonstrated activity in a cellular replicon assay at concentrations comparable to their KD for the RNA target. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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