Synthesis, structure-activity relationship and in vitro biological evaluation of N-arylethyl isoquinoline derivatives as Coxsackievirus B3 inhibitors.

Abstract

Currently, there is no approved antiviral drug for the infection caused by enteroviruses. A series of novel N-arylethyl isoquinoline derivatives defined with substituents on the ring A and C were designed, synthesized and evaluated in vitro for their activities against Coxsackievirus B3 (CVB3). The primary structure-activity relationship revealed that substituents on the ring A were not beneficial for the activity. Among these analogs synthesized, compound 7f bearing a methylenedioxy at the R(4) and R(5) positions afforded an anti-CVB3 activity and a reasonable selectivity index (SI=26.8); furthermore, 7f exhibited a moderate activity against enterovirus 71 (EV71) with SI value of 9.0. Thus it has been selected as an anti-enteroviral lead compound for further investigation.

• Authors: Yan-Xiang Wang, Yu-Huan Li, Ying-Hong Li, Rong-Mei Gao, Hui-Qiang Wang, Yan-Xin Liu, Li-Mei Gao, Qiao-Ni Lu, Jian-Dong Jiang, Dan-Qing Song
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 21 Issue 19 Pg. 5787-90 (Oct 01 2011) ISSN: 1464-3405 [Electronic] England
• PMID: 21880491 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antiviral Agents
• Isoquinolines

Topics

• Animals
• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Chlorocebus aethiops
• Drug Design
• Enterovirus B, Human (drug effects, physiology)
• Inhibitory Concentration 50
• Isoquinolines (chemical synthesis, chemistry, pharmacology)
• Microbial Sensitivity Tests
• Molecular Structure
• Structure-Activity Relationship
• Vero Cells
• Virus Replication (drug effects)