| Autor: |
Verschueren, W. G., Dierynck, I., Amssoms, K. I. E., Hu, L., Boonants, P. M. J. G., Pille, G. M. E., Daeyaert, F. F. D., Hertogs, K., Surleraux, D. L. N. G., Wigerinck, P. B. T. P. |
| Zdroj: |
Journal of Medicinal Chemistry; March 2005, Vol. 48 Issue: 6 p1930-1940, 11p |
| Abstrakt: |
Human immunodeficiency virus type-1 integrase is an essential enzyme for effective viral replication and hence a valid target for the design of inhibitors. We report here on the design and synthesis of a novel series of phthalimide analogues as integrase inhibitors. The short synthetic pathway enabled us to synthesize a series of analogues with a defined structure diversity. The presence of a single carbonyl−hydroxy−aromatic nitrogen motif was shown to be essential for the enzymatic activity and this was confirmed by molecular docking studies. The enzymatically most active compound from this series is 7-(3,4-dichlorobenzyl)-5,9-dihydroxypyrrolo[3,4-g]quinoxaline-6,8-dione (15l) with an IC50 value of 112 nM on the HIV-1 integrase enzyme, while ((7-(4-chlorobenzyl)-5,9-dihydroxy-pyrrolo[3,4-g]quinoxaline-6,8-dione (15k)) showed an EC50 of 270 nM against HIV-1 in a cell-based assay. |
| Databáze: |
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