Abstract
The development of HIV-1 dual inhibitors is a highly innovative approach aimed at reducing drug toxic side effects as well as therapeutic costs. HIV-1 integrase (IN) and reverse transcriptase-associated ribonuclease H (RNase H) are both selective targets for HIV-1 chemotherapy, and the identification of dual IN/RNase H inhibitors is an attractive strategy for new drug development. We newly synthesized pyrrolyl derivatives that exhibited good potency against IN and a moderate inhibition of the RNase H function of RT, confirming the possibility of developing dual HIV-1 IN/RNase H inhibitors and obtaining new information for the further development of more effective dual HIV-1 inhibitors.
Publication types
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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HIV / drug effects*
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HIV / enzymology
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HIV Integrase / metabolism*
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HIV Integrase Inhibitors / chemical synthesis
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HIV Integrase Inhibitors / chemistry
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HIV Integrase Inhibitors / pharmacology*
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / chemistry
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HIV Reverse Transcriptase / metabolism
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Microbial Sensitivity Tests
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Molecular Structure
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Protein Structure, Tertiary / drug effects
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Pyrroles / chemical synthesis
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Pyrroles / chemistry
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Pyrroles / 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*
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Ribonuclease H / antagonists & inhibitors*
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Ribonuclease H / metabolism
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Structure-Activity Relationship
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Virus Replication / drug effects
Substances
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HIV Integrase Inhibitors
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Pyrroles
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Reverse Transcriptase Inhibitors
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HIV Integrase
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HIV Reverse Transcriptase
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Ribonuclease H
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p31 integrase protein, Human immunodeficiency virus 1