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dc.contributor.authorWINDLE, HENRYen
dc.contributor.authorGILMER, JOHN FRANCISen
dc.contributor.authorKELLEHER, DERMOT Pen
dc.contributor.authorKEOGH, BRIANen
dc.contributor.authorREILLY, MARYen
dc.date.accessioned2011-11-15T14:29:39Z
dc.date.available2011-11-15T14:29:39Z
dc.date.issued2011en
dc.date.submitted2011en
dc.identifier.citationMarquez Ruiz JF, Kedziora K, Keogh B, Maguire J, Reilly M, Windle HJ, Kelleher D, Gilmer JF, A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors, Bioorganic & Medicinal Chemistry Letters, 21, 22, 2011, 6636-6640en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/60695
dc.descriptionPUBLISHEDen
dc.description.abstractThe design, synthesis and delivery potential of a new type of benzenesulfonamide cyclo-oxygenase-2 (COX-2) inhibitor prodrug is investigated using celecoxib. The approach involves a double prodrug that is activated first by azoreductases and then by cyclization triggering drug release. We studied the intramolecular aminolysis of the acylsulfonamide. The cyclization was surprisingly rapid at physiological pH and very fast at pH 5. The prodrug is activated specifically under conditions found in the colon but highly stable in the presence of human and rodent intestinal extracts. Finally, the prototype with celecoxib was transported much more slowly in the Caco-2 transepithelial model than the parent. The design therefore shows significant promise for the site specific delivery of benzenesulfonamide COX-2 inhibitors to the colon.en
dc.description.sponsorshipThis work was supported by the Enterprise Ireland and OPSONA Therapeutics LTD under the Innovations Partnership Program (IP/2007/503).en
dc.format.extent6636-6640en
dc.language.isoenen
dc.relation.ispartofseriesBioorganic & Medicinal Chemistry Lettersen
dc.relation.ispartofseries21en
dc.relation.ispartofseries22en
dc.rightsYen
dc.subjectOncologyen
dc.subjectPharmacologyen
dc.subjectCOX-2 inhibitoren
dc.subjectColon canceren
dc.titleA double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitorsen
dc.typeJournal Articleen
dc.contributor.sponsorEnterprise Irelanden
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/kellehdpen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/hjwindleen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/gilmerjfen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/keoghbren
dc.identifier.peoplefinderurlhttp://people.tcd.ie/reillym3en
dc.identifier.rssinternalid75067en
dc.contributor.sponsorGrantNumberIP/2007/503en
dc.identifier.rssurihttp://dx.doi.org/10.1016/j.bmcl.2011.09.071en


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