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dc.contributorWichita State University. Department of Chemistryen_US
dc.contributor.authorPerera, Rohan P.en_US
dc.contributor.authorWimalasena, D. Shyamalien_US
dc.contributor.authorWimalasena, Kandategeen_US
dc.date.accessioned2012-02-06T17:16:11Z
dc.date.available2012-02-06T17:16:11Z
dc.date.issued2003-06-19en_US
dc.identifier12801224en_US
dc.identifier9716531en_US
dc.identifierNS 39423en_US
dc.identifier.citationJournal of medicinal chemistry. 2003 Jun 19; 46(13): 2599-605.en_US
dc.identifier.issn0022-2623en_US
dc.identifier.urihttp://dx.doi.org/10.1021/jm030004pen_US
dc.identifier.urihttp://hdl.handle.net/10057/4319
dc.descriptionClick on the DOI link below to access the article (may not be free).en_US
dc.description.abstractA series of 3-amino-2-phenylpropene (APP) derivatives have been synthesized and characterized as novel competitive inhibitors, with K(i) values in the microM range, for the bovine chromaffin granule membrane monoamine transporter(s) (bVMAT). Although, these inhibitors are structurally similar to the bVMAT substrate tyramine, none of them were measurably transported into the granule. Structure-activity studies have revealed that, while the 3'- or 4'-OH groups on the aromatic ring enhance the inhibition potency, Me or OMe groups in these positions reduce the inhibition potency. Halogen substitution on the 4'-position of the aromatic ring causes gradual increase of the inhibition potency parallel to the electron donor ability of the halogen. Substituents on the NH(2) as well as on the 3-position of the alkyl chain reduce the inhibition potency. Comparative structure-activity analyses of APP derivatives with tyramine and the neurotoxin 1-methyl-4-phenylpyridinium suggest that the flexibility of the side chain and the relative orientation of the NH(2) group may be critical for the efficient transport of the substrate through the bVMAT. Comparable bVMAT affinities of these inhibitors to that of DA and other pharmacologically active amines suggest that they are suitable for the structure-activity and mechanistic studies of monoamine transporters and may also be useful in modeling the mechanism of action of amphetamine-related derivatives.en_US
dc.description.sponsorshipNINDS NIH HHSen_US
dc.format.extent2599-605en_US
dc.language.isoengen_US
dc.publisherAmerican Chemical Societyen_US
dc.relation.ispartofseriesJournal of medicinal chemistryen_US
dc.relation.ispartofseriesJ. Med. Chem.en_US
dc.sourceNLMen_US
dc.subjectIn Vitroen_US
dc.subjectResearch Support, U.S. Gov't, P.H.S.en_US
dc.subject.meshAllyl Compounds/chemical synthesisen_US
dc.subject.meshAnimalsen_US
dc.subject.meshBenzene Derivatives/chemical synthesisen_US
dc.subject.meshBiological Transporten_US
dc.subject.meshCattleen_US
dc.subject.meshChromaffin Granules/metabolismen_US
dc.subject.meshDopamine/metabolismen_US
dc.subject.meshKineticsen_US
dc.subject.meshMembrane Glycoproteins/antagonists & inhibitorsen_US
dc.subject.meshMembrane Transport Proteinsen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshNeuropeptidesen_US
dc.subject.meshSolubilityen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshVesicular Biogenic Amine Transport Proteinsen_US
dc.subject.meshVesicular Monoamine Transport Proteinsen_US
dc.subject.meshWateren_US
dc.subject.meshAllyl Compounds/chemistryen_US
dc.subject.meshAllyl Compounds/pharmacologyen_US
dc.subject.meshBenzene Derivatives/chemistryen_US
dc.subject.meshBenzene Derivatives/pharmacologyen_US
dc.titleCharacterization of a series of 3-amino-2-phenylpropene derivatives as novel bovine chromaffin vesicular monoamine transporter inhibitorsen_US
dc.typeArticleen_US
dc.coverage.spacialUnited Statesen_US
dc.description.versionpeer revieweden_US
dc.rights.holderCopyright © 2003 American Chemical Societyen_US


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