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Wang T, Kadow JF, Zhang Z, Yin Z, Gao Q, Wu D, Parker DD, Yang Z, Zadjura L, Robinson BA, Gong YF, Blair WS, Shi PY, Yamanaka G, Lin PF, Meanwell NA: Inhibitors of HIV-1 attachment. Bioorg Med Chem Lett. 2009 Sep 1;19(17):5140-5. Epub 2009 Jul 18.
Part 4: A study of the effect of piperazine substitution patterns on antiviral potency in the context of indole-based derivatives.. 4-Fluoro- and 4-methoxy-1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl) ethane-1,2-dione (2 and 3, respectively) have been characterized as potent inhibitors of HIV-1 attachment that interfere with the interaction of viral gp120 with the host cell receptor CD4. As part of an effort to understand fundamental aspects of this pharmacophore, discovered originally using a high throughput cell-based screen, modification and substitution of the piperazine ring was examined in the context of compounds 6a-ah. The piperazine ring was shown to be a critical element of the HIV-1 attachment inhibiting pharmacophore, acting as a scaffold to deploy the indole glyoxamide and benzamide in a topographical relationship that complements the binding site on gp120. |
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