Synthesis and Antiviral Evaluation of Cis-Substituted Cyclohexenyl and Cyclohexanyl Nucleosides

Karine Barral (1) , Jérôme Courcambeck (2) , Gérard Pèpe (2) , Jan Balzarini (3) , Johan Neyts (3) , Erik de Clercq (3) , Michel Camplo (1)

1 GCOMM - Groupe de chimie organique et matériaux moléculaires
2 KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven
3 GSP - GenoScience Pharma [Marseille]

Starting from commercially available (rac)-3-cyclohexene-1-carboxylic acid, a series of purine and pyrimidine cis-substituted cyclohexenyl and cyclohexanyl nucleosides were synthesized through a key Mitsunobu reaction. Antiviral evaluations were performed on HIV, coxsackie B3, and herpes viruses (HSV-1, HSV-2, VZV, HCMV). Three compounds showed moderate activity against HSV-1 and coxsackie viruses. Specific computer modeling studies were performed on HSV-1 thymidine kinase in order to understand the enzyme activation of an analogue showing moderate antiviral activity.

Domains: Chemical Sciences; Chemical Sciences; Medicinal Chemistry

Karine Barral, Jérôme Courcambeck, Gérard Pèpe, Jan Balzarini, Johan Neyts, et al.. Synthesis and Antiviral Evaluation of Cis-Substituted Cyclohexenyl and Cyclohexanyl Nucleosides. Journal of Medicinal Chemistry, 2005, 48 (2), pp.450-456. ⟨10.1021/jm0493966⟩. ⟨hal-02061654⟩