Design, efficient synthesis, and anti-HIV activity of 4′-C-cyano- and 4′-C-ethynyl-2′-deoxy purine nucleosides

Satoru Kohgo, Kohei Yamada, Kenji Kitano, Yuko Iwai, Shinji Sakata, Noriyuki Ashida, Hiroyuki Hayakawa, Daisuke Nameki, Eiichi Kodama, Masao Matsuoka, Hiroaki Mitsuya, Hiroshi Ohrui

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

Abstract

Some 4′-C-ethynyl-2′-deoxy purine nucleosides showed the most potent anti-HIV activity among the series of 4′-C-substituted 2′-deoxynucleosides whose 4′-C-substituents were methyl, ethyl, ethynyl and so on. Our hypothesis is that the smaller the substituent at the C-4′ position they have, the more acceptable biological activity they show. Thus, 4′-C-cyano-2′-deoxy purine nucleosides, whose substituent is smaller than the ethynyl group, will have more potent antiviral activity. To prove our hypothesis, we planned to develop an efficient synthesis of 4′-C-cyano-2′-deoxy purine nucleosides (4′-CNdNs) and 4′-C-ethynyl-2′-deoxy purine nucleosides (4′-EdNs). Consequently, we succeeded in developing an efficient synthesis of six 2′-deoxy purine nucleosides bearing either a cyano or an ethynyl group at the C-4′ position of the sugar moiety from 2′-deoxyadenosine and 2,6-diaminopurine 2′-deoxyriboside. Unfortunately, 4′-C-cyano derivatives showed lower activity against HIV-1, and two 4′-C-ethynyl derivatives suggested high toxicity in vivo.

Original languageEnglish
Pages (from-to)671-690
Number of pages20
JournalNucleosides, Nucleotides and Nucleic Acids
Volume23
Issue number4
DOIs
Publication statusPublished - 2004
Externally publishedYes

Keywords

  • 4′-CNdNs
  • 4′-EdNs
  • Anti-HIV-1 agents
  • Efficient synthesis
  • NRTIs

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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