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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
7
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pubmed:dateCreated |
2007-3-29
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pubmed:abstractText |
Novel N-substituted indol-3-ylglyoxylamides (10-37) were synthesized and evaluated as ligands of the benzodiazepine receptor (BzR). In an effort to achieve affinity-based selectivity among BzR subtypes, these compounds were designed to probe the LDi and L2 lipophilic regions. Taking the alpha1-selective benzylindolylglyoxylamides Ia and Ib as leads, we varied the substituent on the benzylamide phenyl ring (compounds 10-23) or replaced the benzyl moiety with alkyl groups (compounds 24-37). The above structural changes gave no shift of selectivity from the alpha1 toward the alpha2 or alpha5 subtypes, thus confirming that a ligand which occupies the LDi region probably exhibits alpha1 selectivity, despite its interactions with other lipophilic areas in the receptor binding cleft. Compound 11 (N-(p-methylbenzyl)-5-nitroindol-3-ylglyoxylamide), which selectively binds with a full agonist efficacy at the alpha1 receptor subtype and displays sedative action, can be regarded as an interesting potential zolpidem-like sedative-hypnotic agent.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0022-2623
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pubmed:author |
pubmed-author:BesnardFrançoisF,
pubmed-author:CalderoneVincenzoV,
pubmed-author:CosimelliBarbaraB,
pubmed-author:Da SettimoFedericoF,
pubmed-author:GrecoGiovanniG,
pubmed-author:La MottaConcettinaC,
pubmed-author:MariniAnna MariaAM,
pubmed-author:MartiniClaudiaC,
pubmed-author:MontaliMarinaM,
pubmed-author:NovellinoEttoreE,
pubmed-author:PatriziMaria PaolaMP,
pubmed-author:PrimofioreGiampaoloG,
pubmed-author:SergianniValentinaV,
pubmed-author:SimoriniFrancescaF,
pubmed-author:TalianiSabrinaS
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pubmed:issnType |
Print
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pubmed:day |
5
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|
pubmed:volume |
50
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pubmed:owner |
NLM
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|
pubmed:authorsComplete |
Y
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pubmed:pagination |
1627-34
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17335185-Amides,
pubmed-meshheading:17335185-Animals,
pubmed-meshheading:17335185-Cattle,
pubmed-meshheading:17335185-Cell Line,
pubmed-meshheading:17335185-Cerebral Cortex,
pubmed-meshheading:17335185-GABA-A Receptor Agonists,
pubmed-meshheading:17335185-Glyoxylates,
pubmed-meshheading:17335185-Hypnotics and Sedatives,
pubmed-meshheading:17335185-Indoles,
pubmed-meshheading:17335185-Ligands,
pubmed-meshheading:17335185-Male,
pubmed-meshheading:17335185-Mice,
pubmed-meshheading:17335185-Mice, Inbred BALB C,
pubmed-meshheading:17335185-Molecular Conformation,
pubmed-meshheading:17335185-Motor Activity,
pubmed-meshheading:17335185-Radioligand Assay,
pubmed-meshheading:17335185-Rats,
pubmed-meshheading:17335185-Structure-Activity Relationship
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pubmed:year |
2007
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pubmed:articleTitle |
Novel N-substituted indol-3-ylglyoxylamides probing the LDi and L1/L2 lipophilic regions of the benzodiazepine receptor site in search for subtype-selective ligands.
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pubmed:affiliation |
Dipartimento di Scienze Farmaceutiche, Università di Pisa, Via Bonanno 6, 56126 Pisa, Italy. primofiore@farm.unipi.it
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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