Article (Scientific journals)
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
Dintilhac, Gaëlle; Arslan, Deniz; Dilly, Sébastien et al.
2011In MedChemComm, 2, p. 509
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Abstract :
[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.
Research center :
Laboratoire de Chimie Pharmaceutique, CIRM, Université de Liège
Institut de recherches Servier
Disciplines :
Computer science
Pharmacy, pharmacology & toxicology
Author, co-author :
Dintilhac, Gaëlle ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Arslan, Deniz ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Dilly, Sébastien ;  Université de Liège - ULiège > 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 ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
De Tullio, Pascal ;  Université de Liège - ULiège > Département de pharmacie > Chimie pharmaceutique
Language :
English
Title :
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
Publication date :
2011
Journal title :
MedChemComm
ISSN :
2040-2503
eISSN :
2040-2511
Publisher :
ROYAL SOC CHEMISTRY, CAMBRIDGE, United Kingdom
Volume :
2
Pages :
509
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 09 June 2011

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