| Autor: |
Tucker TJ; Department of Medicinal Chemistry, Merck Research Laboratories, West Point, Pennsylvania 19486., Lumma WC Jr, Payne LS, Wai JM, de Solms SJ, Giuliani EA, Darke PL, Heimbach JC, Zugay JA, Schleif WA, et. al. |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of medicinal chemistry [J Med Chem] 1992 Jul 10; Vol. 35 (14), pp. 2525-33. |
| DOI: |
10.1021/jm00092a002 |
| Abstrakt: |
A series of HIV-1 protease inhibitors containing a novel hydroxyethyl secondary amine transition state isostere has been synthesized. The compounds exhibit a strong preference for the (R) stereochemistry at the transition state hydroxyl group. Molecular modeling studies with the prototype compound 11 have provided important insights into the structural requirements for good inhibitor-active site binding interaction. N-Terminal extension of 11 into the P2-P3 region led to the discovery of 19, the most potent enzyme inhibitor in the series (IC50 = 5.4 nM). 19 was shown to have potent antiviral activity in cultured MT-4 human T-lymphoid cells. Comparison of analogs of 19 with analogs of 1 (Ro31-8959) demonstrates that considerably different structure-activity relationships exist between these two subclasses of hydroxyethylamine HIV-protease inhibitors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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