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Syntheses of isoxazoline-carbocyclic nucleosides and their antiviral evaluation: a standard protocol.

Quadrelli P, Vazquez Martinez N, Scrocchi R, Corsaro A, Pistarà V - ScientificWorldJournal (2014)

Bottom Line: Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds.No specific antiviral activity was observed in the cases at hand.Novel compounds were prepared for future biological tests.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Chimica, Università degli Studi di Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

ABSTRACT
The current synthesis of racemic purine and pyrimidine isoxazoline-carbocyclic nucleosides is reported, detailing the key-steps for standard and reliable preparations. Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds. Some of the obtained compounds were also evaluated against a wide variety of DNA and RNA viruses including HIV. No specific antiviral activity was observed in the cases at hand. Novel compounds were prepared for future biological tests.

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Mentions: An important aspect of the anti-HIV therapy is the suppression of viral replication in the brain; in this regard an enhanced lipophilicity of potential drugs is likely to be advantageous. Recently, Vince and Hua [6] have reported the modification of the stavudine 3 by fusion of a benzene ring to the carbasugar, leading to analogue 4 [8]. This structural modification increases the lipophilicity (and hence the access to the central nervous system, a major reservoir of HIV) [9] while maintaining the rigidity imposed by the C2′–C3′ double bond. Analogously, carbanucleosides in which an aromatic heterocycle is fused to the carbasugar of carbovir and abacavir have been prepared [10]. Five-membered heterocyclic rings such as a pyrazole [11] or isoxazoline [12] are often found in carbocyclic nucleosides [13] as expedients to tune up the lipophilicity or reduce the conformational flexibility of the carbocyclic moiety (Figure 1) [14].


Syntheses of isoxazoline-carbocyclic nucleosides and their antiviral evaluation: a standard protocol.

Quadrelli P, Vazquez Martinez N, Scrocchi R, Corsaro A, Pistarà V - ScientificWorldJournal (2014)

© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4230217&req=5

Mentions: An important aspect of the anti-HIV therapy is the suppression of viral replication in the brain; in this regard an enhanced lipophilicity of potential drugs is likely to be advantageous. Recently, Vince and Hua [6] have reported the modification of the stavudine 3 by fusion of a benzene ring to the carbasugar, leading to analogue 4 [8]. This structural modification increases the lipophilicity (and hence the access to the central nervous system, a major reservoir of HIV) [9] while maintaining the rigidity imposed by the C2′–C3′ double bond. Analogously, carbanucleosides in which an aromatic heterocycle is fused to the carbasugar of carbovir and abacavir have been prepared [10]. Five-membered heterocyclic rings such as a pyrazole [11] or isoxazoline [12] are often found in carbocyclic nucleosides [13] as expedients to tune up the lipophilicity or reduce the conformational flexibility of the carbocyclic moiety (Figure 1) [14].

Bottom Line: Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds.No specific antiviral activity was observed in the cases at hand.Novel compounds were prepared for future biological tests.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Chimica, Università degli Studi di Pavia, Viale Taramelli 12, 27100 Pavia, Italy.

ABSTRACT
The current synthesis of racemic purine and pyrimidine isoxazoline-carbocyclic nucleosides is reported, detailing the key-steps for standard and reliable preparations. Improved yields were obtained by the proper tuning of the single synthetic steps, opening the way for the preparation of a variety of novel compounds. Some of the obtained compounds were also evaluated against a wide variety of DNA and RNA viruses including HIV. No specific antiviral activity was observed in the cases at hand. Novel compounds were prepared for future biological tests.

Show MeSH
Related in: MedlinePlus