Synthesis and Antiviral Activity of Some C₂-, C₄-, and C₆-Substituted Pyrazolo[3,4-D]Pyrimidine Acyclonucleosides with the Alkylating Chains of ACV, HBG, and ISO-DHPG

Abstract

A useful route to obtain trisubstituted pyrazolo[3,4-d]pyrimidines 14–17 is described. Those later were coupled with the alkylating agents 18–20 as in ACV, HBG, and iso-DHPG to give, after deprotection, the desired acylonucleosides 33–44. Almost all of the new compounds were evaluated for their inhibitory effects against the replication of various DNA viruses in culture.

Keywords:

• C_2-, C_4-, and C₆-substituted pyrazolo[3,4-d]pyrimidines
• Acyclonucleoside
• Analogues of ACV, HBG, and iso-DHPG

This investigation was supported by Ibn Zoher University, Faculty of Sciences, Agadir, Morocco. We thank Mr. Kristien Erven (Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium) for excellent technical assistance with the antiviral assays.

Notes

^a MCC: minimum cytotoxic concentration: required to cause a microscopically detectable alteration of normal cell morphology.

^b Required to reduce virus-induced cytopathogenecity by 50%.

^a MCC: minimum cytotoxic concentration: required to cause a microscopically detectable alteration of normal cell morphology.

^b Required to reduce virus-induced cytopathogenecity by 50%.

^a Inhibitory concentration required to reduce virus plaque formation by 50%. Virus input was 100 plaque-forming units (PFU).

^b MCC: minimum cytotoxic concentration: required to cause a microscopically detectable alteration of normal cell morphology.

^c Required to reduce virus-induced cytopathogenecity by 50%.

^a Inhibitory concentration required to reduce virus plaque formation by 50%. Virus input was 100 plaque-forming units (PFU).

^b Minimum cytotoxic concentration required to cause a microscopically detectable alteration of normal cell morphology.

^c Required to reduce virus-induced cytopathogenecity by 50%.

Key: s (singlet), d (doublet), t (triplet), m (multiplet), and br (broad).