Creation of Low Toxic Reverse-transcriptase Inhibitory Nucleosides that Prevent the Emergence of Drug-resistant HIV Variants

• Ohrui Hiroshi

  Yokohama Pharmaceutical College

• Hayakawa Hiroyuki

  Yamasa Corporation

• Kohgo Satoru

  Yamasa Corporation

• Matsuoka Masao

  Institute for Virus Research, Kyoto University

• Kodama Eiichi

  Institute for Virus Research, Kyoto University

• Mitsuya Hiroaki

  Kumamoto University, School of Medicine NIH, NCI

Bibliographic Information

Other Title

• 耐性ＨＩＶを発現させない低毒性逆転写酵素阻害ヌクレオシドの創製研究
• タイセイ HIV オ ハツゲン サセナイ テイドクセイ ギャクテンシャ コウソ ソガイ ヌクレオシド ノ ソウセイ ケンキュウ

Abstract

Although the Highly Active Anti-Retroviral Therapy (HAART) has dramatically improved the quality of life and the prognosis of patients infected with HIV, development of more active and less toxic drugs that prevent the emergence of drug-resistant HIV variants is strongly required, due to the emergence of new drug-resistant HIV variants, need of taking a large quantity of drugs, and side effects of the drugs.<BR>The principal author has proposed a concept to prevent the emergence of the HIV variants resistant to reverse-transcriptase (RT) inhibitory nucleosides. Based on the concept, 4'-C-substituted-2'-deoxynucleoside (4'Sd-N) was designed as the anti-HIV nucleoside that could prevent the emergence of resistant HIV variants. Various kinds of 4'Sd-N were synthesized and evaluated for biological activity.<BR>2'-Deoxy-4'-C-ethynyl-2-fluoroadenosine (4'Ed-2FA) which is stable to adenosine deaminase turned out to be highly active against all HIV-1 including multi-drug resistant variants and very lowly toxic, and so far no HIV-1 variants resistant to it emerged. These results suggest that once-daily-dosing schedule of 4'Ed-2FA is possible presumably with few side effects and warrant that 4'Ed-2FA be further developed as a potential therapeutic for HIV-1 infection.

Journal

• Journal of Synthetic Organic Chemistry, Japan

  Journal of Synthetic Organic Chemistry, Japan 64 (7), 716-723, 2006

  The Society of Synthetic Organic Chemistry, Japan

Keywords

• AIDS
• HIV
• anti-HIV-1 drug free from emergence of resistant HIV-1 variant
• RT-inhibitory nucleoside
• drug-resistant HIV
• prevention of the emergence of drug-resistant HIV
• highly active anti-retroviral therapy (HAART)
• 4'-C-substituted-2'-deoxynucleoside

Details

• CRID: 1390001205312916992
• NII Article ID: 10017617749
• NII Book ID: AN0024521X
• DOI: 10.5059/yukigoseikyokaishi.64.716
• ISSN: 18836526
• ISSN: 00379980
• NDL BIB ID: 8032129
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I8032129
• Text Lang: ja
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed