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dc.contributor.authorCappelli, A
dc.contributor.authorAnzini, M
dc.contributor.authorCastriconi, F
dc.contributor.authorGrisci, G
dc.contributor.authorPaolino, M
dc.contributor.authorBraile, C
dc.contributor.authorValenti, S
dc.contributor.authorGiuliani, G
dc.contributor.authorVomero, S
dc.contributor.authorDi Capua, A
dc.contributor.authorBetti, L
dc.contributor.authorGiannaccini, G
dc.contributor.authorLucacchini, A
dc.contributor.authorGhelardini, C
dc.contributor.authorDi Cesare Mannelli, L
dc.contributor.authorFrosini, M
dc.contributor.authorRicci, L
dc.contributor.authorGiorgi, G
dc.contributor.authorMascia, MP
dc.contributor.authorBiggio, G
dc.date.accessioned2017-08-14T03:27:49Z
dc.date.available2017-08-14T03:27:49Z
dc.date.issued2016
dc.identifier.issn0022-2623
dc.identifier.doi10.1021/acs.jmedchem.6b00034
dc.identifier.urihttp://hdl.handle.net/10072/343964
dc.description.abstractA series of imidazo[1,5-a]quinoline derivatives was designed and synthesized as central benzodiazepine receptor (CBR) ligands. Most of the compounds showed high CBR affinity with Ki values within the submicromolar and subnanomolar ranges with interesting modulations in their structure–affinity relationships. In particular, fluoroderivative 7w (Ki = 0.44 nM) resulted in the most potent ligand among the imidazo[1,5-a]quinoline derivatives described so far. Overall, these observations confirmed the assumption concerning the presence of a large though apparently saturable lipophilic pocket in the CBR binding site region interacting with positions 4 and 5 of the imidazo[1,5-a]quinoline nucleus. The in vivo biological characterization revealed that compounds 7a,c,d,l,m,q,r,w show anxiolytic and antiamnestic activities without the unpleasant myorelaxant side effects of the classical 1,4-BDZ. Furthermore, the effect of 7l,q,r, and 8i in lowering lactate dehydrogenase (LDH) release induced by ischemia-like conditions in rat brain slices suggested neuroprotective properties for these imidazo[1,5-a]quinoline derivatives.
dc.description.peerreviewedYes
dc.languageeng
dc.publisherAmerican Chemical Society
dc.relation.ispartofpagefrom3353
dc.relation.ispartofpageto3372
dc.relation.ispartofissue7
dc.relation.ispartofjournalJournal of Medicinal Chemistry
dc.relation.ispartofvolume59
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry not elsewhere classified
dc.subject.fieldofresearchMedicinal and Biomolecular Chemistry
dc.subject.fieldofresearchPharmacology and Pharmaceutical Sciences
dc.subject.fieldofresearchOrganic Chemistry
dc.subject.fieldofresearchcode030499
dc.subject.fieldofresearchcode0304
dc.subject.fieldofresearchcode1115
dc.subject.fieldofresearchcode0305
dc.titleDesign, Synthesis, and Biological Evaluation of Imidazo[1,5-a]quinoline as Highly Potent Ligands of Central Benzodiazepine Receptors
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
gro.hasfulltextNo Full Text
gro.griffith.authorDi Capua, Angela


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