A NEW CLASS OF ACYCLIC NUCLEOSIDE PHOSPHONATES: SYNTHESIS AND BIOLOGICAL ACTIVITY OF 9-{[(PHOSPHONOMETHYL)AZIRIDIN-1-YL]METHYL}GUANINE (PMAMG) AND ANALOGUES

We report here a general method for the synthesis of new symmetrical bis-phosphonates of acyclic nucleosides. 1,3-Bis[(diisopropoxyphosphoryl)methoxy] derivatives of purine and pyrimidine bases were prepared by their reaction with 1,3-bis[(diisopropoxyphosphoryl)-methoxy]propan-2-yl tosylate. Cytosine, uracil and thymine provided regiospecificallyN1-isomers. This alkylation regiospecificity applies to several other tosylates of primary and secondary alcohols as well. 6-Chloropurine and 2-amino-6-chloropurine were alkylated in N9position. Resulting bis-phosphonates were converted to the respective free phosphonic acids and tested for antiviral and cytostatic activity. Despite the fact that no biological activity was found so far, the outcome of this work can serve as a useful tool in synthesis of novel groups of acyclic nucleoside phosphonates (ANPs).

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Sonogashira Cross-Coupling in the Synthesis of Acyclic Nucleoside Phosphonates: Preparation of 6-[(Phosphonomethoxy)alkynyl]- and 6-[(Phosphonomethoxy)alkyl]pyrimidines

Collection of Czechoslovak Chemical Communications ◽

10.1135/cccc20050247 ◽

2005 ◽

Vol 70 (2) ◽

pp. 247-258 ◽

Cited By ~ 7

Author(s):

Dana Hocková ◽

Milena Masojídková ◽

Antonín Holý

Keyword(s):

Biological Activity ◽

Coupling Reaction ◽

Cross Coupling ◽

Cross Coupling Reaction ◽

Acyclic Nucleoside Phosphonates ◽

Acyclic Nucleoside

Several 6-[(phosphonomethoxy)alkyl]pyrimidines and 6-[(phosphonomethoxy)alkynyl]pyrimidines were prepared as saturated and unsaturated carba-analogues of antivirally active 2,4-diamino-6-[2-(phosphonomethoxy)ethoxy]pyrimidine. As the key step of their synthesis the Sonogashira cross-coupling reaction was successfully applied. The replacement of the C-O moiety by the C-C bond resulted in the loss of biological activity.

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Inhibitory Activities of Three Classes of Acyclic Nucleoside Phosphonates against Murine Polyomavirus and Primate Simian Virus 40 Strains

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01422-06 ◽

2007 ◽

Vol 51 (6) ◽

pp. 2268-2273 ◽

Cited By ~ 25

Author(s):

Ilya Lebeau ◽

Graciela Andrei ◽

Marcela Krečmerová ◽

Erik De Clercq ◽

Antonin Holý ◽

...

Keyword(s):

Simian Virus 40 ◽

Simian Virus ◽

New Class ◽

Acyclic Nucleoside Phosphonates ◽

Murine Polyomavirus ◽

Inhibitory Activities ◽

Acyclic Nucleoside

ABSTRACT Murine polyomavirus and simian virus 40 were used to evaluate the potencies of the compounds of three classes of acyclic nucleoside phosphonates: (i) the original HPMP (3-hydroxy-2-phosphonomethoxypropyl) and PME (2-phosphonomethoxyethyl) derivatives, (ii) the 6-[2-(phosphonomethoxy)alkoxy]-2,4-diaminopyrimidine (DAPy) derivatives, and (iii) a new class of HPMP derivatives containing a 5-azacytosine moiety. The last class showed the highest activities and selectivities against both polyomaviruses.

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