title: Development of modified nucleosides that have supremely high anti-HIV activity and low toxicity and prevent the emergence of resistant HIV mutants.
abstract: An idea to use 4'-C-substituted-2'-deoxynucleoside derivatives was proposed based on a working hypothesis to solve the problems of existing acquired immune deficiency syndrome chemotherapy (highly active antiretroviral therapy). Subsequent studies have successfully proved the validity of the idea and resulted in the development of 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine and 2'-deoxy-4'-C-ethynyl-2-chloroadenosine, nucleoside reverse transcriptase inhibitors, which have supremely high activity against all human immunodeficiency viruses including multidrug-resistant HIV and low toxicity.
authors.affiliation: Yokohama College of Pharmacy, Kanagawa, Japan. h.ohrui@hamayaku.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ohrui
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D055808:Drug Discovery / Q000379:methods*; D024882:Drug Resistance, Viral / Q000187:drug effects* / Q000235:genetics*; D006678:HIV / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D009154:Mutation / Q000187:drug effects*; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D019380:Anti-HIV Agents; D019384:Nucleic Acid Synthesis Inhibitors; D009705:Nucleosides