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dc.contributor.authorRYDER, SHEILAen
dc.date.accessioned2013-07-09T11:54:42Z
dc.date.available2013-07-09T11:54:42Z
dc.date.issued2010en
dc.date.submitted2010en
dc.identifier.citationDillon GP, Gaynor JM, Khan D, Carolan CG, Ryder SA, Marquez JF, Reidy S, Gilmer JF, Isosorbide-based cholinesterase inhibitors; replacement of 5-ester groups leading to increased stability, Bioorg Med Chem, 18, 3, 2010, 1045 - 1053en
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/66664
dc.descriptionPUBLISHEDen
dc.descriptionPMID: 20093035en
dc.description.abstractIsosorbide-2-carbamate-5-esters are highly potent and selective butyrylcholinesterase inhibitors with potential utility in the treatment of Alzheimer?s Disease (AD). They are stable in human plasma but in mouse plasma they undergo hydrolysis at the 5-ester group potentially attenuating in vivo potency. In this paper we explore the role of the 5-position in modulating potency. The focus of the study was to increase metabolic stability while preserving potency and selectivity. Dicarbamates and 5-keto derivatives were markedly less potent than the ester class. The 2-benzylcarbamate-5-benzyl ether was found to be potent (IC50 52 nM) and stable in the presence of mouse plasma and liver homogenate. The compound produces sustained moderate inhibition of mouse butyrylcholinesterase at 1 mg/kg, IP.en
dc.format.extent1045en
dc.format.extent1053en
dc.language.isoenen
dc.relation.ispartofseriesBioorg Med Chemen
dc.relation.ispartofseries18en
dc.relation.ispartofseries3en
dc.rightsYen
dc.subjectButyrylcholinesterase inhibitoren
dc.subjectSelectivityen
dc.subjectMetabolic stabilityen
dc.subject.lcshButyrylcholinesteraseen
dc.subject.lcshInhibitorsen
dc.subject.lcshEnzyme inhibitorsen
dc.subject.lcshCholinesterase inhibitorsen
dc.subject.lcshDrug stabilityen
dc.subject.lcshStabilityen
dc.titleIsosorbide-based cholinesterase inhibitors; replacement of 5-ester groups leading to increased stabilityen
dc.typeJournal Articleen
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/sryderen
dc.identifier.rssinternalid68567en
dc.identifier.doihttp://dx.doi.org/10.1016/j.bmc.2009.12.052en
dc.subject.TCDThemeNeuroscienceen
dc.identifier.rssuri3en


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