Synthesis and Antiviral Activity of Acyclic Nucleotide Analogues Derived from 6-(Aminomethyl)purines and Purine-6-carboxamidines

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Title:Synthesis and Antiviral Activity of Acyclic Nucleotide Analogues Derived from 6-(Aminomethyl)purines and Purine-6-carboxamidines
Creators:
Hocek, Michal
Masojídková, Milena
Holý, Antonín
Andrei, Graciela
Snoeck, Robert
Balzarini, Jan
De Clercq, Erik
Journal or Publication Title:
Collection of Czechoslovak Chemical Communications, 61, 10, pp. 1525-1537
Uncontrolled Keywords:Antivirals, 6-Cyanopurines, Acyclic nucleoside phosphonates, Purine-6-carboxamidines, 6-(Aminomethyl)purines, Phosphonomethoxyalkylpurine derivatives

Abstract

The synthesis of a series of 9-(2-phosphonomethoxyalkyl) derivatives of 6-(aminomethyl)purine <strong>11</strong>, 2-amino-6-(aminomethyl)purine <strong>12 </strong>and purine-6-carboxamidine <strong>14</strong> is reported. The 6-cyanopurines <strong>1</strong> and <strong>2</strong> were selectively alkylated with 2-[bis(isopropyloxy)phosphonylmethoxy]alkyl synthons <strong>3</strong> and <strong>4</strong> at the 9-position. Catalytic hydrogenation of the obtained 9-{2-[bis(isopropyloxy)phosphonylmethoxy]alkyl}-6-cyanopurines <strong>9</strong> and <strong>10</strong> followed by treatment with bromotrimethylsilane afforded the title compounds <strong>11</strong> and <strong>12</strong>. Analogous acyclic nucleotides derived from purine-6-carboxamidines <strong>14</strong> were prepared from the cyanopurines <strong>9a</strong> and <strong>10a</strong> by treatment with sodium methoxide and ammonium chloride followed by deprotection. Compounds <strong>11</strong> and <strong>12</strong> exhibited moderate activity (MIC<sub>50</sub> = 3-50 μg/ml) against herpes simplex virus type 1, varicella-zoster virus and Moloney murine sarcoma virus in vitro.

Title:Synthesis and Antiviral Activity of Acyclic Nucleotide Analogues Derived from 6-(Aminomethyl)purines and Purine-6-carboxamidines
Creators:
Hocek, Michal
Masojídková, Milena
Holý, Antonín
Andrei, Graciela
Snoeck, Robert
Balzarini, Jan
De Clercq, Erik
Uncontrolled Keywords:Antivirals, 6-Cyanopurines, Acyclic nucleoside phosphonates, Purine-6-carboxamidines, 6-(Aminomethyl)purines, Phosphonomethoxyalkylpurine derivatives
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:61
Number:10
Page Range:pp. 1525-1537
ISSN:0010-0765
E-ISSN:1212-6950
Publisher:Institute of Organic Chemistry and Biochemistry
Related URLs:
URLURL Type
http://dx.doi.org/10.1135/cccc19961525UNSPECIFIED
ID Code:1056
Item Type:Article
Deposited On:06 Feb 2009 17:06
Last Modified:06 Feb 2009 16:06

Citation

Hocek, Michal; Masojídková, Milena; Holý, Antonín; Andrei, Graciela; Snoeck, Robert; Balzarini, Jan; De Clercq, Erik (1996) Synthesis and Antiviral Activity of Acyclic Nucleotide Analogues Derived from 6-(Aminomethyl)purines and Purine-6-carboxamidines. Collection of Czechoslovak Chemical Communications, 61 (10). pp. 1525-1537. ISSN 0010-0765

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