Nucleosides. 146. 1-methyl-5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent L-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6 Journal Article

  

Authors:	Pankiewicz, K. W.; Nawrot, B.; Gadler, H.; Price, R. W.; Watanabe, K. A.
Article Title:	Nucleosides. 146. 1-methyl-5-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)uracil, the C-nucleoside isostere of the potent antiviral agent L-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)thymine (FMAU). Studies directed toward the synthesis of 2'-deoxy-2'-substituted arabino nucleosides. 6
Abstract:	The synthesis of 5-(2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (1, C-FMAU), an isostere of the potent antiviral and antitumor nucleoside 1-(2-deoxy-2-fluoro-/?-D-arabinofuranosyl)thymine (2'-fluoro-5-methyl-ara-U or FMAU), was achieved. Pseudouridine (2) was converted into 4,5'-anhydro-3'-0-acetyl-2'-0-triflylpseudouridine (4), which was treated with tris(dimethylamino)sulfur(l+) difluorotrimethylsilicate (TASF) to give 4,5'-anhydro-5-(3-0-acetyl-2-deoxy-2-fluoro-/3-D-arabinofuranosyl)-l-methyluracil (5b) in 40% yield. Acid hydrolysis of the 4,5'-anhydro linkage of 5b with Dowex 50 (H+) afforded C-FMAU. The inhibitory activity of C-FMAU against HSV-1 and HSV-2 was about 10-fold less than that of FMAU in tissue culture. This compound, however, did not show significant activity in mice inoculated with HSV-1 or HSV-2. © 1987, American Chemical Society. All rights reserved.
Keywords:	unclassified drug; nonhuman; mouse; animal; mice; animal experiment; animal model; in vitro study; mice, inbred balb c; simplexvirus; arabinofuranosyluracil; herpes simplex virus 1; therapy; uridine; antiviral agents; herpes simplex virus 2; drug comparison; human; female; support, u.s. gov't, p.h.s.; preliminary communication; 2' fluorothymine arabinoside; drug analysis; 5 (2 deoxy 2 fluoro beta d arabinofuranosyl) 1 methyluracil
Journal Title:	Journal of Medicinal Chemistry
Volume:	30
Issue:	12
ISSN:	0022-2623
Publisher:	American Chemical Society
Date Published:	1987-12-01
Start Page:	2314
End Page:	2316
Language:	English
DOI:	10.1021/jm00395a023
PUBMED:	2824777
PROVIDER:	scopus
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-0023618704&doi=10.1021%2fjm00395a023&partnerID=40&md5=dbe83218a976bfdc05d9b699ffa2402b
Notes:	Article -- Export Date: 5 February 2021 -- Source: Scopus

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