Reference : New substituted aryl esters and aryl amides of 3,4-dihydro-2H-1,2,4- benzothiadiazine...
Scientific journals : Article
Engineering, computing & technology : Computer science
Human health sciences : Pharmacy, pharmacology & toxicology
http://hdl.handle.net/2268/92688
New substituted aryl esters and aryl amides of 3,4-dihydro-2H-1,2,4- benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors
English
Dintilhac, Gaëlle mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
Arslan, Deniz mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique > >]
Dilly, Sébastien mailto [Université de Liège - ULg > Département de Pharmacie > Chimie Pharmaceutique > >]
Danober, Laurence [Institut de recherches Servier > > > >]
Botez, Iuliana [Institut de recherches Servier > > > >]
Lestage, Pierre [Institut de recherches Servier > > > >]
Pirotte, Bernard mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
De Tullio, Pascal mailto [Université de Liège - ULg > Département de pharmacie > Chimie pharmaceutique >]
2011
MedChemComm
ROYAL SOC CHEMISTRY
2
509
Yes (verified by ORBi)
International
2040-2503
2040-2511
CAMBRIDGE
ENGLAND
[en] AMPA receptor potentiators belonging to 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been found to be of great interest as cognitive enhancers. Previous structure–activity relationships have demonstrated the importance for activity of the nature of the substituent at the 7-position of the heterocycle. This work aims to explore the impact on AMPA potentiation of the introduction of different aryl and aralkyl ester or aryl amide groups at the 7-position. The new synthesized compounds were evaluated as AMPA receptor potentiators by examining their effect on rat brain primary cell cultures on AMPA-evoked membrane depolarisation using fluorescent membrane potential dyes and on imaging-based plate reader. The most potent compound of this series was 2-methylphenyl 4-methyl- 3,4-dihydro-2H-1,2,4-benzothiadiazine-7-carboxylate 1,1-dioxide 16c which provoked a strong potentiation of AMPA current with a potency close to that reported for the best reference compounds of the benzothiadiazine class (i.e cyclothiazide). This work also revealed that only the ortho-substitution of the phenyl group of 1,2,4-benzothiadiazine-7-carboxylate esters provided potent AMPA receptor potentiators opening the way to further chemical exploration.
Laboratoire de Chimie Pharmaceutique, CIRM, Université de Liège ; Institut de recherches Servier
Researchers ; Professionals ; Students
http://hdl.handle.net/2268/92688

File(s) associated to this reference

Fulltext file(s):

FileCommentaryVersionSizeAccess
Restricted access
Dintilhac-MedChemComm-2011.pdfPublisher postprint325.94 kBRequest copy

Bookmark and Share SFX Query

All documents in ORBi are protected by a user license.