Abstract
Our efforts to reduce overall lipophilicity and increase ligand-lipophilicity efficiency (LLE) by modification of the 3- and 5-substituents of pyrazole 1, a novel non-nucleoside HIV reverse transcriptase inhibitor (NNRTI) prototype were unsuccessful. In contrast replacement of the substituted benzyl group with corresponding phenylthio or phenoxy groups resulted in marked improvements in potency, ligand efficiency (LE) and LLE.
MeSH terms
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Anti-HIV Agents / chemical synthesis
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Anti-HIV Agents / chemistry*
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Anti-HIV Agents / pharmacology
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Chemical Phenomena
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Drug Design
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / metabolism
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Humans
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Microsomes, Liver / metabolism
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Pyrazoles / chemical synthesis
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Pyrazoles / chemistry*
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Pyrazoles / pharmacology
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Reverse Transcriptase Inhibitors / chemical synthesis
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Reverse Transcriptase Inhibitors / chemistry*
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Reverse Transcriptase Inhibitors / pharmacology
Substances
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Anti-HIV Agents
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Pyrazoles
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Reverse Transcriptase Inhibitors
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pyrazole
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reverse transcriptase, Human immunodeficiency virus 1
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HIV Reverse Transcriptase