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dc.contributor.advisorLever, Susan Z., 1952-eng
dc.contributor.authorFan, Kuo-Hsieneng
dc.date.issued2010eng
dc.date.submitted2010 Falleng
dc.descriptionTitle from PDF of title page (University of Missouri--Columbia, viewed on April 21, 2014).eng
dc.description.abstractSigma receptors are unique binding sites located in the central nervous system (CNS) and peripheral organs. Two sigma receptor subtypes ([signma]1 and [sigma]2) have been described so far. It is known that the [sigma]1 receptor is involved in a number of CNS disorders and the [sigma]2 receptor is involved in tumor proliferation among others. Because of the important biological functions of the [sigma] receptor, development of structure activity relationships (SAR) can aid in the identification of potential medications and imaging agents. Three series of analogs based on three lead compounds have been synthesized and evaluated for their in vitro affinity and selectivity for the [sigma]1 and [sigma]2 subtypes. Lead I is a selective [sigma]1 receptor ligand with anti-cocaine activity, but its in vivo distribution is unknown. Our in vitro binding results showed that all the Lead I analogs are potent [sigma]1 receptor ligands. Furthermore, one of the Lead I analogs was radioiodinated and evaluated for its in vivo distribution. In vivo evaluation of the radioiodinated Lead I analog has shown high brain uptake and specific binding to [sigma]1 receptor of the radioligand. Lead II is also a selective [sigma]1 receptor ligand and radioiodinated Lead II has been shown to be a potential imaging agent for the [sigma]1 receptor. Two of the Lead II analogs were shown to be potent [sigma]1 receptor ligands. The radioiodinated Lead II analogs were demonstrated to be potential imaging agents for [sigma]1 receptor in vivo. Lead III is one of the most selective [sigma]2 receptor ligands known to date. Only one of the newly synthesized Lead III analogs was found to be a selective [sigma]2 receptor ligand. The SAR study of Lead III analogs successfully indentified the important structural features in Lead III for [sigma]2 receptor binding. To summarize, the SAR studies based on the lead compounds have generated useful information and three potential [sigma]1 imaging agents were prepared in the studies.eng
dc.format.extentxv, 291 pageseng
dc.identifier.urihttps://hdl.handle.net/10355/41910
dc.identifier.urihttps://doi.org/10.32469/10355/41910eng
dc.languageEnglisheng
dc.publisherUniversity of Missouri--Columbiaeng
dc.relation.ispartofcommunityUniversity of Missouri--Columbia. Graduate School. Theses and Dissertationseng
dc.rightsOpenAccess.eng
dc.rights.licenseThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License.
dc.subjectSigma receptoreng
dc.subjectStructure-activity relationshipeng
dc.subjectRadioiodinationeng
dc.subjectImaging agentseng
dc.subjectBinding assayseng
dc.subjectBiodistributioneng
dc.subject.FASTSigma receptorseng
dc.subject.FASTBinding sites (Biochemistry) -- Analysiseng
dc.subject.FASTCocaine -- Physiological aspectseng
dc.titleSynthesis and evaluation of sigma receptor ligandseng
dc.typeThesiseng
thesis.degree.disciplinePlant sciences (MU)eng
thesis.degree.grantorUniversity of Missouri--Columbiaeng
thesis.degree.levelDoctoraleng
thesis.degree.namePh. D.eng


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