Synthesis and biological evaluation of [D-lysine]8cyclosporin A analogs as potential anti-HCV agents

Andrew Scribner; David Houck; Zhuhui Huang; Sarah Mosier; Michael Peel; Bernard Scorneaux

doi:10.1016/j.bmcl.2010.09.036

Synthesis and biological evaluation of [D-lysine]8cyclosporin A analogs as potential anti-HCV agents

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6542-6. doi: 10.1016/j.bmcl.2010.09.036. Epub 2010 Sep 21.

Authors

Andrew Scribner¹, David Houck, Zhuhui Huang, Sarah Mosier, Michael Peel, Bernard Scorneaux

Affiliation

¹ SCYNEXIS, Inc., PO Box 12878, Research Triangle Park, NC 27709-2878, USA. andrew.scribner@scynexis.com

PMID: 20943390
DOI: 10.1016/j.bmcl.2010.09.036

Abstract

An efficient synthesis of [D-lysine](8)cyclosporin A has been developed. Several analogs of [D-lysine](8)cyclosporin A have been synthesized and show promising anti-HCV activity, particularly compounds 39 and 43, which each exhibit an anti-HCV EC(50)<200 nM, and are each ≥50-fold less immunosuppressive than cyclosporin A.

MeSH terms

Antiviral Agents / chemical synthesis*
Antiviral Agents / pharmacology*
Crystallography, X-Ray
Cyclosporine / chemical synthesis*
Cyclosporine / pharmacology*
Hepacivirus / drug effects*
Models, Molecular

Substances

Antiviral Agents
Cyclosporine