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dc.creatorClayton, Terry
dc.creatorPoe, Michael M.
dc.creatorRallapalli, Sundari
dc.creatorBiawat, Poonam
dc.creatorSavić, Miroslav
dc.creatorRowlett, James K.
dc.creatorGallos, George
dc.creatorEmala, Charles
dc.creatorKaczorowski, Catherine C.
dc.creatorStafford, Douglas C.
dc.creatorArnold, Leggy
dc.creatorCook, James M.
dc.date.accessioned2019-09-02T11:44:38Z
dc.date.available2019-09-02T11:44:38Z
dc.date.issued2015
dc.identifier.issn2090-2069
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2317
dc.description.abstractAn updated model of the GABA(A) benzodiazepine receptor pharmacophore of the alpha 5-BzR/GABA(A) subtype has been constructed prompted by the synthesis of subtype selective ligands in light of the recent developments in both ligand synthesis, behavioral studies, and molecular modeling studies of the binding site itself. A number of BzR/GABA(A) alpha 5 subtype selective compounds were synthesized, notably alpha 5-subtype selective inverse agonist PWZ-029 (1) which is active in enhancing cognition in both rodents and primates. In addition, a chiral positive allosteric modulator (PAM), SH-053-2'F-R-CH3 (2), has been shown to reverse the deleterious effects in the MAM-model of schizophrenia as well as alleviate constriction in airway smooth muscle. Presented here is an updated model of the pharmacophore for alpha 5 beta 2 gamma 2 Bz/GABA(A) receptors, including a rendering of PWZ-029 docked within the alpha 5-binding pocket showing specific interactions of the molecule with the receptor. Differences in the included volume as compared to alpha 1 beta 2 gamma 2, alpha 2 beta 2 gamma 2, and alpha 3 beta 2 gamma 2 will be illustrated for clarity. These new models enhance the ability to understand structural characteristics of ligands which act as agonists, antagonists, or inverse agonists at the Bz BS of GABA(A) receptors.en
dc.publisherHindawi Ltd, London
dc.relationMilwaukee Institute for Drug Design
dc.rightsopenAccess
dc.sourceInternational Journal of Medicinal Chemistry
dc.titleA Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Modelen
dc.typearticle
dc.rights.licenseBY
dcterms.abstractAрнолд, Леггy; Савић, Мирослав; Кацзороwски, Цатхерине Ц.; Пое, Мицхаел М.; Цлаyтон, Террy; Раллапалли, Сундари; Биаwат, Поонам; Роwлетт, Јамес К.; Емала, Цхарлес; Цоок, Јамес М.; Стаффорд, Доуглас Ц.; Галлос, Георге;
dc.identifier.wos000364585300001
dc.identifier.doi10.1155/2015/430248
dc.identifier.pmid26682068
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/1029/2315.pdf
dc.identifier.rcubconv_3378
dc.type.versionpublishedVersion


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