Design, synthesis, and biological evaluation of novel coxsackievirus B3 inhibitors

Michal Sála; Armando M De Palma; Hubert Hrebabecký; Radim Nencka; Martin Dracínský; Pieter Leyssen; Johan Neyts; Antonín Holý

doi:10.1016/j.bmc.2010.04.081

Design, synthesis, and biological evaluation of novel coxsackievirus B3 inhibitors

Bioorg Med Chem. 2010 Jun 15;18(12):4374-84. doi: 10.1016/j.bmc.2010.04.081. Epub 2010 Apr 29.

Authors

Michal Sála¹, Armando M De Palma, Hubert Hrebabecký, Radim Nencka, Martin Dracínský, Pieter Leyssen, Johan Neyts, Antonín Holý

Affiliation

¹ Gilead Sciences & IOCB Research Centre, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.

PMID: 20576576
DOI: 10.1016/j.bmc.2010.04.081

Abstract

The synthesis and SAR study of a novel class of coxsackievirus B3 (CVB3) inhibitors are reported. These compounds could be considered as the 6-chloropurines substituted at position 9 with variously substituted bicyclic scaffolds (bicyclo[2.2.1]heptane/ene-norbornane or norbornene). The synthesis and biological evaluation of 31 target compounds are described. Several of the analogues inhibited CVB3 in the low micromolar range (0.66-2muM). Minimal or no cytotoxicity was observed.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antiviral Agents / chemical synthesis*
Antiviral Agents / chemistry
Antiviral Agents / pharmacology
Bridged Bicyclo Compounds / chemical synthesis
Bridged Bicyclo Compounds / chemistry
Bridged Bicyclo Compounds / pharmacology
Chlorocebus aethiops
Drug Design
Enterovirus B, Human / drug effects*
Humans
Purines / chemical synthesis
Purines / chemistry*
Purines / pharmacology
Structure-Activity Relationship
Vero Cells

Substances

Antiviral Agents
Bridged Bicyclo Compounds
Purines
bicyclo(2.2.1)heptene
6-chloropurine