- Synthesis and biological activity of 3'-azido- and 3'-amino substituted nucleoside analogs
-
The product distribution obtained in the reaction of 1-(5-0-trityl-0-mesyl-2-deoxy-β-D-erythro-pentofuranosyl)-2,4-(1H, 3H)-pyrimidinedione with lithium azide in N, N'-dimethylformamide at 100°C depends on the nature of the substituent in 5. The results may be explained by a difference in the acidity of the pyrimidinedione. The reaction of the more acidic nucleosides (X = I, F) appears to proceed preferentially through the 2,3'-anhydro intermediate, whereas for the less acidic products (X = H, CH3) direct nucleophilic displacement by the azide ion predominates. The different 3'-azidfo derivatives were reduced to 3'-amino compounds. All 3'-azido- and 3'-aminopyrimidine nucleosides were tested against herpes simplex virus, vaccinia and vesicular stomatitis virus and on murine L1210 cell growth. None of the substances exhibited significant activity.
- Colla,Herdewijn,De Clercq,et al.
-
p. 295 - 301
(2007/10/02)
-
- Synthesis and Biological Activity of Various 3'-Azido and 3'-Amino Analogues of 5-Substituted Pyrimidine Deoxyribonucleosides
-
Various new 5-substituted 3'-azido- and 3'-amino derivatives of 2'-deoxyuridine and 2'-deoxycytidine have been synthesized and biologically evaluated.Among these compounds, 3'-amino-2',3'-dideoxy-5-fluorouridine (3), 3'-amino-2',3'-dideoxycytidine (7a), and 3'-amino-2',3'-dideoxy-5-fluorocytidine (7c) were found to be the most active against murine L1210 and sarcoma 180 neoplastic cells in vitro, with an ED50 of 15 and 1 μM, 0.7 and 4 μM, and 10 and 1 μM, respectively.The 3'-azido derivatives, 2 and 6c, were less active in comparison with their 3'-amino counterparts.In addition, the 5-fluoro-3'-amino nucleosides, 3 and 7c, were tested against L1210 leukemia bearing CDF1 mice.Our preliminary findings indicate that compound 7c (6 * 200 mg/kg) was as active as the positive control, 5-fluorouracil (6 * 20 mg/kg), yielding a T/C * 100 of 146 and 129, respectively.However, 3 was found to be inactive in this experiment.
- Lin, Tai-Shun,Gao, You-Song,Mancini, William R.
-
p. 1691 - 1696
(2007/10/02)
-