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
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 p...
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| Veröffentlicht in: | Journal of medicinal chemistry 2007-04, Vol.50 (7), p.1442-1444 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 50 |
| creator | Bailey, Thomas R Rippin, Susan R Opsitnick, Elizabeth Burns, Christopher J Pevear, Daniel C Collett, Marc S Rhodes, Gerry Tohan, Sanjeev Huggins, John W Baker, Robert O Kern, Earl R Keith, Kathy A Dai, Dongcheng Yang, Guang Hruby, Dennis Jordan, Robert |
| description | 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. |
| doi_str_mv | 10.1021/jm061484y |
| format | Article |
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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.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm061484y</identifier><identifier>PMID: 17335190</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Washington, DC: American Chemical Society</publisher><subject>Administration, Oral ; Animals ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Antiviral agents ; Antiviral Agents - chemical synthesis ; Antiviral Agents - pharmacokinetics ; Antiviral Agents - pharmacology ; Benzamides - chemical synthesis ; Benzamides - pharmacokinetics ; Benzamides - pharmacology ; Biological and medical sciences ; Biological Availability ; Cell Line ; Crystallography, X-Ray ; Humans ; In Vitro Techniques ; Indoles - chemical synthesis ; Indoles - pharmacokinetics ; Indoles - pharmacology ; Isoindoles ; Macaca fascicularis ; Medical sciences ; Mice ; Molecular Structure ; Orthopoxvirus - drug effects ; Orthopoxvirus - physiology ; Pharmacology. Drug treatments ; Rats ; Stereoisomerism ; Structure-Activity Relationship</subject><ispartof>Journal of medicinal chemistry, 2007-04, Vol.50 (7), p.1442-1444</ispartof><rights>Copyright © 2007 American Chemical Society</rights><rights>2007 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a471t-e99f60c6c73d6a7f2582ed5948efe266e40217dde4d2aedd89b02467771daa4c3</citedby><cites>FETCH-LOGICAL-a471t-e99f60c6c73d6a7f2582ed5948efe266e40217dde4d2aedd89b02467771daa4c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm061484y$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm061484y$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>230,314,780,784,885,2763,27075,27923,27924,56737,56787</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=18676723$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17335190$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bailey, Thomas R</creatorcontrib><creatorcontrib>Rippin, Susan R</creatorcontrib><creatorcontrib>Opsitnick, Elizabeth</creatorcontrib><creatorcontrib>Burns, Christopher J</creatorcontrib><creatorcontrib>Pevear, Daniel C</creatorcontrib><creatorcontrib>Collett, Marc S</creatorcontrib><creatorcontrib>Rhodes, Gerry</creatorcontrib><creatorcontrib>Tohan, Sanjeev</creatorcontrib><creatorcontrib>Huggins, John W</creatorcontrib><creatorcontrib>Baker, Robert O</creatorcontrib><creatorcontrib>Kern, Earl R</creatorcontrib><creatorcontrib>Keith, Kathy A</creatorcontrib><creatorcontrib>Dai, Dongcheng</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Hruby, Dennis</creatorcontrib><creatorcontrib>Jordan, Robert</creatorcontrib><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</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>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.</description><subject>Administration, Oral</subject><subject>Animals</subject><subject>Antibiotics. Antiinfectious agents. Antiparasitic agents</subject><subject>Antiviral agents</subject><subject>Antiviral Agents - chemical synthesis</subject><subject>Antiviral Agents - pharmacokinetics</subject><subject>Antiviral Agents - pharmacology</subject><subject>Benzamides - chemical synthesis</subject><subject>Benzamides - pharmacokinetics</subject><subject>Benzamides - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Biological Availability</subject><subject>Cell Line</subject><subject>Crystallography, X-Ray</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Indoles - chemical synthesis</subject><subject>Indoles - pharmacokinetics</subject><subject>Indoles - pharmacology</subject><subject>Isoindoles</subject><subject>Macaca fascicularis</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Molecular Structure</subject><subject>Orthopoxvirus - drug effects</subject><subject>Orthopoxvirus - physiology</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNptkc2KE0EUhRtRnDi68AWkN8IEurT-uqrbhSDD_ARC4s84LkSKm6rq6cp0ukJVJyQ7tz6EL-eT2JKQKLi6i_Pdcy_nJMlzgl8RTMnr-QILwgu-fZAMSE4x4gXmD5MBxpQiKig7SZ7EOMcYM0LZ4-SESMZyUuJB8nOCzljGIOMZhyzPcshEJgBNdQf11gSPSMaQcX7jEc8ESm1X29brrW78Mvjl1-qbi961xjeIojNyPUTbZqghzPwGFs7Y-ObX9x_pyNi2c5XT0Dnfpr5KJ35tm3Qautov_WbtwiqmF3fBxpiO2trNXOdDfJo8qqCJ9tl-niafLy9uzq_ReHo1On83RsAl6ZAty0pgLbRkRoCsaF5Qa_KSF7ayVAjL-5SkMZYbCtaYopxhyoWUkhgArtlp8nbnu1zNFtbo_tkAjVoGt4CwVR6c-ldpXa3u_FpxLCTGojcY7gx08DEGWx12CVZ_OlKHjnr2xd_HjuS-lB54uQcgamiqAK128cgVQgpJWc-hHediZzcHHcK9EpLJXN28_6Q-fhl_oLcTom6PvqCjmvtVaPtM__Pgb4HLtkU</recordid><startdate>20070405</startdate><enddate>20070405</enddate><creator>Bailey, Thomas R</creator><creator>Rippin, Susan R</creator><creator>Opsitnick, Elizabeth</creator><creator>Burns, Christopher J</creator><creator>Pevear, Daniel C</creator><creator>Collett, Marc S</creator><creator>Rhodes, Gerry</creator><creator>Tohan, Sanjeev</creator><creator>Huggins, John W</creator><creator>Baker, Robert O</creator><creator>Kern, Earl R</creator><creator>Keith, Kathy A</creator><creator>Dai, Dongcheng</creator><creator>Yang, Guang</creator><creator>Hruby, Dennis</creator><creator>Jordan, Robert</creator><general>American Chemical Society</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20070405</creationdate><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</title><author>Bailey, Thomas R ; Rippin, Susan R ; Opsitnick, Elizabeth ; Burns, Christopher J ; Pevear, Daniel C ; Collett, Marc S ; Rhodes, Gerry ; Tohan, Sanjeev ; Huggins, John W ; Baker, Robert O ; Kern, Earl R ; Keith, Kathy A ; Dai, Dongcheng ; Yang, Guang ; Hruby, Dennis ; Jordan, Robert</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a471t-e99f60c6c73d6a7f2582ed5948efe266e40217dde4d2aedd89b02467771daa4c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Administration, Oral</topic><topic>Animals</topic><topic>Antibiotics. Antiinfectious agents. Antiparasitic agents</topic><topic>Antiviral agents</topic><topic>Antiviral Agents - chemical synthesis</topic><topic>Antiviral Agents - pharmacokinetics</topic><topic>Antiviral Agents - pharmacology</topic><topic>Benzamides - chemical synthesis</topic><topic>Benzamides - pharmacokinetics</topic><topic>Benzamides - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Biological Availability</topic><topic>Cell Line</topic><topic>Crystallography, X-Ray</topic><topic>Humans</topic><topic>In Vitro Techniques</topic><topic>Indoles - chemical synthesis</topic><topic>Indoles - pharmacokinetics</topic><topic>Indoles - pharmacology</topic><topic>Isoindoles</topic><topic>Macaca fascicularis</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Molecular Structure</topic><topic>Orthopoxvirus - drug effects</topic><topic>Orthopoxvirus - physiology</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bailey, Thomas R</creatorcontrib><creatorcontrib>Rippin, Susan R</creatorcontrib><creatorcontrib>Opsitnick, Elizabeth</creatorcontrib><creatorcontrib>Burns, Christopher J</creatorcontrib><creatorcontrib>Pevear, Daniel C</creatorcontrib><creatorcontrib>Collett, Marc S</creatorcontrib><creatorcontrib>Rhodes, Gerry</creatorcontrib><creatorcontrib>Tohan, Sanjeev</creatorcontrib><creatorcontrib>Huggins, John W</creatorcontrib><creatorcontrib>Baker, Robert O</creatorcontrib><creatorcontrib>Kern, Earl R</creatorcontrib><creatorcontrib>Keith, Kathy A</creatorcontrib><creatorcontrib>Dai, Dongcheng</creatorcontrib><creatorcontrib>Yang, Guang</creatorcontrib><creatorcontrib>Hruby, Dennis</creatorcontrib><creatorcontrib>Jordan, Robert</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bailey, Thomas R</au><au>Rippin, Susan R</au><au>Opsitnick, Elizabeth</au><au>Burns, Christopher J</au><au>Pevear, Daniel C</au><au>Collett, Marc S</au><au>Rhodes, Gerry</au><au>Tohan, Sanjeev</au><au>Huggins, John W</au><au>Baker, Robert O</au><au>Kern, Earl R</au><au>Keith, Kathy A</au><au>Dai, Dongcheng</au><au>Yang, Guang</au><au>Hruby, Dennis</au><au>Jordan, Robert</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>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</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2007-04-05</date><risdate>2007</risdate><volume>50</volume><issue>7</issue><spage>1442</spage><epage>1444</epage><pages>1442-1444</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><coden>JMCMAR</coden><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.</abstract><cop>Washington, DC</cop><pub>American Chemical Society</pub><pmid>17335190</pmid><doi>10.1021/jm061484y</doi><tpages>3</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| ispartof | Journal of medicinal chemistry, 2007-04, Vol.50 (7), p.1442-1444 |
| issn | 0022-2623 1520-4804 |
| language | eng |
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| source | MEDLINE; ACS Publications |
| subjects | Administration, Oral Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - chemical synthesis Antiviral Agents - pharmacokinetics Antiviral Agents - pharmacology Benzamides - chemical synthesis Benzamides - pharmacokinetics Benzamides - pharmacology Biological and medical sciences Biological Availability Cell Line Crystallography, X-Ray Humans In Vitro Techniques Indoles - chemical synthesis Indoles - pharmacokinetics Indoles - pharmacology Isoindoles Macaca fascicularis Medical sciences Mice Molecular Structure Orthopoxvirus - drug effects Orthopoxvirus - physiology Pharmacology. Drug treatments Rats Stereoisomerism Structure-Activity Relationship |
| 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 |
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