Development of a mass spectrometry method for the determination of a melanoma biomarker, 5-S-cysteinyldopa, in human plasma using solid phase extraction for sample clean-up.

in Journal of Chromatography. A (2007), 1156(1-2), 141-8

5-S-cysteinyldopa is a well-known pigment intermediate and analysis of its plasma concentration is interesting for the early diagnosis, as well as for evaluation of treatment and follow-up of malignant ... [more ▼]

5-S-cysteinyldopa is a well-known pigment intermediate and analysis of its plasma concentration is interesting for the early diagnosis, as well as for evaluation of treatment and follow-up of malignant melanoma. A determination method of 5-SCD in human plasma was developed using solid phase extraction (SPE) on disposable cartridges and liquid chromatography electrospray mass spectrometry (LC-ESI-MS-MS). Compound's sensitivity to light and oxidation requires the addition of anti-oxidative agents (AO), to work in acidic media at 4 degrees C and to avoid light exposure of samples since blood collection. Different solid phases involving covalent binding to phenylboronic groups or dual retention mechanisms were evaluated and extraction cartridges containing both hydrophobic and strong cation exchange functionalities were finally selected. The LC separation of 5-SCD from endogenous catecholamines was achieved by gradient elution on a C18 stationary phase. 5-SCD was detected by multiple reaction monitoring (MRM) performed on ES(+) generated ions. Finally, the method was prevalidated in the lower ng/ml range. Good results with respect to accuracy, trueness and precision were obtained. [less ▲]

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)

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

Conference (2006, November 17)

Design, synthesis and pharmacological evaluation of novel 7-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides acting as AMPA potentiators

Poster (2006, August)

Nouveaux développements dans le domaine des activateurs des canaux potassiques ATP-dépendants en série benzopyrane

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

Synthesis and pharmacological evaluation of some N-arylsulfonyl-N-methyl-N'-(2,2-dimethyl-2-H-1-benzopyran-4-yl)ureas structurally related to cromakalim

in Bioorganic & Medicinal Chemistry (2006), 14