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Basic Characteristics of Mutations
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Mutation Site
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Y181C |
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Mutation Site Sentence
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Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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RT |
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Standardized Encoding Gene
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gag-pol:155348
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Genotype/Subtype
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HIV-1 |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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-
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Immune
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- |
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Target Gene
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-
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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NNRTIs |
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Location
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- |
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Literature Information
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PMID
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30788976
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Title
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Synthesis and anti-human immunodeficiency virus activity of substituted ( o,o-difluorophenyl)-linked-pyrimidines as potent non-nucleoside reverse transcriptase inhibitors
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Author
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Cechova L,Dejmek M,Baszczynski O,Saman D,Gao L,Hu E,Stepan G,Jansa P,Janeba Z,Simon P
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Journal
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Antiviral chemistry & chemotherapy
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Journal Info
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2019 Jan-Dec;27:2040206619826265
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Abstract
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With the worldwide number of human immunodeficiency virus positive patients stagnant and the increasing emergence of viral strains resistant to current treatment, the development of novel anti-human immunodeficiency virus drug candidates is a perpetual quest of medicinal chemists. Herein, we report a novel group of diarylpyrimidines, non-nucleoside reverse transcriptase inhibitors, which represents an important class of current anti-human immunodeficiency virus therapy. Series of diarylpyrimidines containing o, o-difluorophenyl (A-arm), 4-cyanophenylamino (B-arm), and a small substituent (e.g. NH(2), OMe) at positions 2, 4, and 6 of the pyrimidine ring were prepared. The A-arm was modified in the para position (F or OMe) and linked to the central pyrimidine core with a variable spacer (CO, O, NH). Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. To the most promising structural motives belong the o, o-difluoro- p-methoxy A-arm in position 4, and the amino group in position 6 of pyrimidine. Single digit nanomolar activities with no significant toxicity (CC(50) > 17,000 nM) were found for compounds 35 (EC(50) = 2 nM), 37 (EC(50) = 3 nM), and 13 (EC(50) = 4 nM) having O, NH, and CO linkers, respectively.
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Sequence Data
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-
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