Synthesis and Biological Activity of N4-Methyl-5-azacytidines

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Title:Synthesis and Biological Activity of N4-Methyl-5-azacytidines
Creators:
Hanna, Naeem B.
Masojídková, Milena
Pískala, Alois
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 63, 5, pp. 713-722
Uncontrolled Keywords:Antitumor activity, Nucleosides, 1,3,5-Triazines, 5-Azapyrimidines, 5-Azacytidines

Abstract

Protected <i>N</i><sup>4</sup>-methyl and <i>N</i><sup>4</sup>,<i>N</i><sup>4</sup>-dimethyl derivatives of 5-azacytidine <strong>3</strong> and <strong>4</strong> were prepared by selective aminolysis of benzoylated 4-methoxy-1-(β-D-ribofuranosyl)-1,3,5-triazin-2(1<i>H</i>)-one <strong>5</strong>, by glycosylation of silylated <i>N</i><sup>4</sup>-methyl- or <i>N</i><sup>4</sup>,<i>N</i><sup>4</sup>-dimethyl-5-azacytosines <strong>7</strong> and <strong>8</strong> with 2,3,5-tri-<i>O</i>-benzoyl-α,β-D-ribofuranosyl chloride (<strong>11</strong>) or by several modifications of the isocyanate method. By the isocyanate approach, also the α-D anomer of protected <i>N</i><sup>4</sup>-methyl-5-azacytidine <strong>17</strong> was obtained as a minor product. The protected dimethyl derivative <strong>4</strong> was also obtained by the reaction of isobiuret <strong>22</strong> with dimethylformamide dimethyl acetal. The free nucleosides <strong>1</strong> and <strong>2</strong> were obtained either by aminolysis of the free methoxy nucleoside <strong>23</strong> with methylamine or dimethylamine, respectively, or by methanolysis or ammonolysis of the corresponding benzoyl derivatives <strong>3</strong> and <strong>4</strong>. The free α-D anomer <strong>24</strong> was obtained by methanolysis of its tribenzoate <strong>17</strong>. Nucleosides <strong>1</strong> and <strong>2</strong> exhibited a lower antibacterial, antitumor and antiviral activity than the unsubstituted 5-azacytidine.

Title:Synthesis and Biological Activity of N4-Methyl-5-azacytidines
Creators:
Hanna, Naeem B.
Masojídková, Milena
Pískala, Alois
Uncontrolled Keywords:Antitumor activity, Nucleosides, 1,3,5-Triazines, 5-Azapyrimidines, 5-Azacytidines
Divisions:Life and Chemical Sciences > Institute of Organic Chemistry and Biochemistry > Collection of Czechoslovak Chemical Communications
Journal or Publication Title:Collection of Czechoslovak Chemical Communications
Volume:63
Number:5
Page Range:pp. 713-722
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19980713UNSPECIFIED
ID Code:1335
Item Type:Article
Deposited On:06 Feb 2009 17:08
Last Modified:06 Feb 2009 16:08

Citation

Hanna, Naeem B.; Masojídková, Milena; Pískala, Alois (1998) Synthesis and Biological Activity of N4-Methyl-5-azacytidines. Collection of Czechoslovak Chemical Communications, 63 (5). pp. 713-722. ISSN 0010-0765

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