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Nucleosides and Nucleotides, Part 144 Synthesis and Antiviral Activity of 5‐Substituted (2′ S )‐2′‐Deoxy‐2′‐ C ‐Methylcytidines and ‐uridines [1]
Author(s) -
Awano Hirokazu,
Shuto Satoshi,
Miyashita Takanori,
Ashida Noriyuki,
Machida Haruhiko,
Kira Toshihiko,
Shigeta Shiro,
Matsuda Akira
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290203
Subject(s) - chemistry , herpes simplex virus , stereochemistry , varicella zoster virus , deoxygenation , nucleoside , cytotoxicity , virus , derivative (finance) , nucleotide , in vitro , virology , biochemistry , biology , gene , economics , financial economics , catalysis
Synthesis of several 5‐substituted (2′ S )‐2′‐deoxy‐2′‐ C ‐methylcytidines ( 8 ) and ‐uridines ( 6, 11 ) has been accomplished using radical deoxygenation of the 2′‐ tert ‐alcohols via their methyl oxalyl esters as a key reaction. Anti‐herpes simplex virus type‐1 and ‐2, and anti‐varicella‐zoster virus activities of the newly synthesized nucleosides were evaluated. Among them, the 5‐iodouracil derivative 6e showed the most potent activity against herpes simplex virus type‐1, with an EC 50 of 0.14 μg/mL without showing cytotoxicity up to 100 μg/mL, but had a weak activity against herpes simplex virus type‐2 and no activity against varicella‐zoster virus up to 50 μg/mL in vitro. Although the 5‐fluorocytosine derivative 8b had a potent anti‐herpes simplex virus type‐1 activity (EC 50 = 0.22 μg/mL), it was rather cytotoxic to the CCRF‐HSB‐2 human T‐cell line (IC 50 ≥ 1.0 μg/mL).