Synthesis and biological evaluation of 9-(5′,5′-difluoro- 5′-phosphonopentyl)guanine derivatives for PNP-inhibitors

Sadao Hikishima, MacHiko Isobe, Koyanagi Satoru, Shinji Soeda, Hiroshi Shimeno, Shiroshi Shibuya, Tsutomu Yokomatsu

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

9-(5′,5′-Difluoro-5′-phosphonopentyl)guanine (DFPP-G) and its hypoxanthine analogue (DFPP-H) were modified by introducing a methyl group to all possible positions of the linker connecting a purine and difluoromethylenephosphonic acid moiety to evaluate the effects of the methyl group on inhibition against purine nucleoside phosphorylase. The methyl group on the linker affected the inhibition in a positional-dependent manner. Inhibitory potency of α-methyl and β-methyl-substituted analogues of DFPP-H increased by about 600- to 1000-fold upon converting to cyclopropane nucleotide analogue (±)-4.

Original languageEnglish
Pages (from-to)1660-1670
Number of pages11
JournalBioorganic and Medicinal Chemistry
Volume14
Issue number5
DOIs
Publication statusPublished - Mar 1 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

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