Abstract
We report herein the development of a new three-dimensional pharmacophore model for HIV-1 integrase inhibitors which led to the discovery of some 4-[1-(4-fluorobenzyl)-1H-indol-3-yl]-2-hydroxy-4-oxobut-2-enoic acids that are able to specifically inhibit the strand transfer step of integration at nanomolar concentration. The synthesis of the new designed molecules is also described.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Butyrates / chemical synthesis
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Butyrates / pharmacology*
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Drug Design*
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Drug Resistance, Viral
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HIV Integrase / drug effects*
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HIV Integrase / metabolism
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HIV Integrase Inhibitors / chemical synthesis
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HIV Integrase Inhibitors / pharmacology*
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HIV-1 / drug effects*
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HIV-1 / growth & development
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Indoles / chemical synthesis
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Indoles / pharmacology*
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Models, Chemical
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Structure-Activity Relationship
Substances
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Butyrates
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HIV Integrase Inhibitors
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Indoles
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HIV Integrase