SYNTHESIS AND BIOLOGICAL-ACTIVITY OF CERTAIN 4'-THIO-D-ARABINOFURANOSYLPURINE NUCLEOSIDES

Citation
Ja. Secrist et al., SYNTHESIS AND BIOLOGICAL-ACTIVITY OF CERTAIN 4'-THIO-D-ARABINOFURANOSYLPURINE NUCLEOSIDES, Journal of medicinal chemistry, 41(20), 1998, pp. 3865-3871
Citations number
36
Categorie Soggetti
Chemistry Medicinal
ISSN journal
00222623
Volume
41
Issue
20
Year of publication
1998
Pages
3865 - 3871
Database
ISI
SICI code
0022-2623(1998)41:20<3865:SABOC4>2.0.ZU;2-C
Abstract
A series of 4'-thio-n-arabinofuranosylpurine nucleosides was prepared and evaluated as potential anticancer agents. The details of a conveni ent and high-yielding synthesis of the carbohydrate precursor acetyl-2 ,3,5-tri-O-benzyl-4-thio-D-arabinofuranose (6) are presented. Proof of structure and configuration at all chiral centers of the nucleosides was obtained through an X-ray crystal structure of 9 alpha as well as through NOE experiments on 9 beta and 9 alpha. All six target compound s were evaluated in a series of human cancer cell lines in culture. Tw o target compounds, beta anomers with diaminopurine (12) and guanine ( 16) as the bases, had significant cytotoxicity. One of these compounds (12) was selected for animal studies but was found to have no selecti vity at the maximum tolerated dose in the murine colon 36 tumor model.