New piperazinyl polyazacyclophane scaffolds, libraries and biological activities.
Four novel unsymmetric piperazinyl polyazacyclophane scaffolds 1-4 were synthesized in high yields by an efficient cyclization strategy. Twenty-six libraries 12-37 (total 16,000 compounds) were generated by a solution-phase combinatorial approach from 1-4 and thirty-eight functional groups. Potent antibacterial and HIV-1 tat/TAR protein-RNA disrupting activities were discovered.
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Isis Pharmaceuticals, Inc., Carlsbad, CA 92008, USA.
Haly
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Cook
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D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001426:Bacterial Proteins / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002628:Chemoreceptor Cells; D019992:Databases as Topic; D015195:Drug Design; D004926:Escherichia coli / Q000187:drug effects; D029968:Escherichia coli Proteins; D015696:Gene Products, tat / Q000378:metabolism; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D008565:Membrane Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012367:RNA, Viral / Q000378:metabolism; D011956:Receptors, Cell Surface; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D029968:Escherichia coli Proteins; D015696:Gene Products, tat; D006146:Guanidines; D007202:Indicators and Reagents; D008565:Membrane Proteins; D010879:Piperazines; D012367:RNA, Viral; D011956:Receptors, Cell Surface; C057331:Tar protein, E coli; D054322:tat Gene Products, Human Immunodeficiency Virus