Inhibitors of kynurenine aminotransferase and uses therefor

Details Inhibitors of kynurenine aminotransferase and uses therefor Inhibitors of kynurenine aminotransferase and uses therefor

C - Chemistry, Metallurgy

07

C

C07C 55/00 (2006.01) C07C 55/06 (2006.01)

Patent

CA 2631623

Provided herein are methods of decreasing a level of kynurenic acid in a cell and of treating a pathophysiological condition in a subject associated with an increase in kynurenic acid in a subject. In these methods the inhibitory action of dicarboxylic acids or derivatives or analogs thereof are effective to inhibit activity of kynurenine aminotrans-ferase II. Also provided is a method of screening for potential inhibitory compounds for kynurenine aminotransferase II. The dicarboxylic acids or derivatives or analogs thereof may have the structural formula, where R1 is H, NH2 or NHCH3, R2 is H or CH3, n is 0 to 14, and X is -COOH, CH2OH, -PO3H2, -SO2H, or -SO3H; or a pharmacologically accept-able salt.

La présente invention concerne des méthodes de diminution de la teneur en acide kynurénique dans une cellule, et de traitement d'un état pathophysiologique chez un sujet associé à une augmentation du taux d'acide kynurénique. Dans ces méthodes, l'effet inhibiteur des acides dicarboxyliques ou des dérivés ou analogues desdits acides permet d'inhiber l'activité de la kynurénine aminotransférase II. La présente invention concerne également une méthode de recherche par criblage de composés inhibiteurs potentiels de la kynurénine aminotransférase II. Les acides dicarboxyliques ou les dérivés ou analogues desdits acides peuvent avoir la formule structurelle, dans laquelle R<SUP>1</SUP> représente H, NH<SUB>2</SUB> ou NHCH<SUB>3</SUB>, R<SUP>2</SUP> représente H ou CH<SUB>3</SUB>, n est compris entre 0 et 14 inclus, et X représente -COOH, CH<SUB>2</SUB>OH, -PO<SUB>3</SUB>H<SUB>2</SUB>, -SO<SUB>2</SUB>H ou-SO<SUB>3</SUB>H ; ou un sel de qualité pharmaceutique.

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