N -(3,3a,4,4a,5,5a,6,6a-Octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1 H )-yl)carboxamides:  Identification of Novel Orthopoxvirus Egress Inhibitors

作者：T. R. Bailey, Susan R. Rippin, Elizabeth Opsitnick, Christopher J. Burns, Daniel C. Pevear, Marc S. Collett, Gerry Rhodes, Sanjeev Tohan, John W. Huggins, Robert O. Baker, Earl R. Kern, Kathy A. Keith, Dongcheng Dai, Guang Yang, Dennis E. Hruby, Robert Jordan · 发表于：Journal of Medicinal Chemistry · 年份：2007 · DOI：10.1021/jm061484y · 被引用次数：66 · 研究领域：Poxvirus research and outbreaks、Plant Virus Research Studies、Herpesvirus Infections and Treatments

A series of novel, potent orthopoxvirus egress inhibitors was identified during high-throughput screening of the ViroPharma small molecule collection. Using structure--activity relationship information inferred from early hits, several compounds were synthesized, and compound 14 was identified as a potent, orally bioavailable first-in-class inhibitor of orthopoxvirus egress from infected cells. Compound 14 has shown comparable efficaciousness in three murine orthopoxvirus models and has entered Phase I clinical trials.