Development of cognitive enhancers acting through AMPA potentiation: design of novel benzothiadiazine 1,1-dioxides with improved pharmacokinetic profile

Conference (2008, May)

Application of LC-SPE-NMR to the structural determination of metabolites of KATP channel openers belonging to 3-alkylamino-4H-1,2,4-arylthiadiazine 1,1-dioxides

Conference (2007, October)

Coupling of the LC-MS/MS and the LC-SPE-NMR for the structural identification of pancreatic KATP channel openers metabolites following in vitro biotransformation

Poster (2007)

Design, synthesis, and pharmacology of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides as positive allosteric modulators of AMPA receptors

in Journal of Medicinal Chemistry (2007), 50(13), 3153-3157

A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the ... [more ▼]

A series of 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides have been synthesized and evaluated as potentiators of AMPA receptors. Attention was paid to the impact of the substituent introduced at the 7-position of the heterocycle. The biological evaluation was achieved by measuring the AMPA current in rat cortex mRNA-injected Xenopus oocytes. The most potent compound, 4-ethyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide (12a) was found to be active in an object recognition test in rats demonstrating cognition enhancing effects in vivo after oral administration. [less ▲]

Novel dipyrazoles acting as glutamate modulators

in Expert Opinion on Therapeutic Patents (2007), 17(12), 1489-1493

Knowing the potential therapeutic interest of AMPA potentiation, patents have been published for 15 years relating the discovery of novel compounds able to allosterically bind to the AMPA receptors and ... [more ▼]

Knowing the potential therapeutic interest of AMPA potentiation, patents have been published for 15 years relating the discovery of novel compounds able to allosterically bind to the AMPA receptors and leading to a potentiation of the AMPA signals. Besides this classical approach, a new target for the medicinal chemist has been defined due to the recent findings describing the modulation of AMPA receptors by neuronal proteins, and has led to the design of dipyrazole compounds by Aventis. These new dipyrazole derivatives may be considered as `indirect AMPApams', constituting a new pharmacological class. Based on their in vitro activity, it is probable that these compounds could be of therapeutic value for the treatment of cognitive disorders, schizophrenia or depression. [less ▲]

In vitro metabolisation study of several 3-alkylamino-4H-1,2,4-benzothiadiazine 1,1-dioxides as ATP-sensitive potassium channel openers : combined use of LC-Q-TOF MS/MS and LC-SPE-NMR

Poster (2006, November 18)

Combined use of LC-SPE-NMR and LC-MS for the metabolites characterization of ATP-sensitive potassium channel openers belonging to 3-alkylamino-4H-1,2,4-arylthiadiazine 1,1-dioxides

Poster (2006, August)

Design, synthèse et évaluation pharmacologique de 1,2,4-pytridothiadiazine 1,1-dioxydes en tant que nouveaux potentiateurs AMPA

Poster (2006, June)

Application of LC-SPE-NMR and LC-Q-TOF MS/MS to the structural determination of KATP channel openers metabolites belonging to the 3-alkylamino-4H-1,2,4-arylthiadiazine 1,1-dioxides

Poster (2006, May 17)

Selective pancreatic ATP-sensitive potassium channel openers for the treatement of glucose homeostasis disorders

in Drugs of the Future (2006), 31