title: N-(3,3a,4,4a,5,5a,6,6a-Octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1H)-yl)carboxamides: Identification of novel orthopoxvirus egress inhibitors.
abstract: 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.
authors.affiliation: ViroPharma Incorporated, 397 Eagleview Boulevard, Exton, Pennsylvania 19341, USA. tbailey@cephalon.com
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Bailey
authors.forename: Susan R
authors.initials: SR
authors.lastname: Rippin
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Opsitnick
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Burns
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Pevear
authors.forename: Marc S
authors.initials: MS
authors.lastname: Collett
authors.forename: Gerry
authors.initials: G
authors.lastname: Rhodes
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Tohan
authors.forename: John W
authors.initials: JW
authors.lastname: Huggins
authors.forename: Robert O
authors.initials: RO
authors.lastname: Baker
authors.forename: Earl R
authors.initials: ER
authors.lastname: Kern
authors.forename: Kathy A
authors.initials: KA
authors.lastname: Keith
authors.forename: Dongcheng
authors.initials: D
authors.lastname: Dai
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Dennis
authors.initials: D
authors.lastname: Hruby
authors.forename: Robert
authors.initials: R
authors.lastname: Jordan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D054833:Isoindoles; D008252:Macaca fascicularis; D051379:Mice; D015394:Molecular Structure; D018155:Orthopoxvirus / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D010797:Phthalimides
chemical_list: D000998:Antiviral Agents; D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; C505045:tecovirimat; D010797:Phthalimides