Novel Substituted-1?-quinazoline-2,4-dione derivatives, preparation method thereof and pharmaceutical composition containing the same

摘要

A novel substituted-1H-quinazoline-2,4-dione derivative is provided which shows excellent selectivity to a 5-HT6 receptor compared to other receptors, and inhibits the concentration increase of cAMP caused by 5-HT and apomorphine -induced hyperactivity of a rat, thereby being usefully used for central nervous system diseases related to the 5-HT6 receptor. A method for preparing a substituted-1H-quinazoline-2,4-dione derivative represented by the formula(1) comprises the steps of: (a) reacting anthranilic acid anhydride represented by the formula(2) with an amine compound to prepare an intermediate represented by the formula(I); (b) subjecting the intermediate of the formula(I) to cyclization to obtain an intermediate represented by the formula(II); (c) reacting the intermediate of the formula(II) with a compound represented by the formula(5) to prepare the derivative of the formula(1). In the formulae, each R^1, R^2 and R^3 is independently H, halogen, amino, cycloamino, nitro, cyano, alkyl, haloalkyl, alkoxy, haloalkoxy, piperazinyl, or N-methyl piperazinyl; R^4 is H, alkyl, cycloalkyl, haloalkyl, aryl, heteroaryl, aralkyl, heteroarylalkyl, alkoxy, aryloxy, acyl amino, arylsulfonylamino, arylsulfonylureido, alkylcarboxylate, arylcarboxylate, aralkylcarboxylate, alkylureido, or arylureido; R^5 is H, alkyl, cycloalkyl, haloalkyl, aryl, arylalkyl, heteroaryl or heteroarylalkyl; R^6 is H, alkyl or aryl; X is F, Cl, Br, I or trifluoroacetate; and Y is Cl, Br, I, methane sulfonate, or p-toluenesulfonate. A pharmaceutical composition as an antagonist of 5-HT6 serotonin receptor comprises the compound of the formula(1), a pharmaceutically acceptable salt thereof or a prodrug thereof as an effective ingredient.