3-Dimercaptoalkylpyrimidin-2,4-(1H,3H)-dione als Matrix Metalloproteinase (MMP) Inhibitoren

Die Erfindung betrifft dimercaptoalkylsubstituierte kondensierte Pyrimidin-2,4(1H,3H)-dione der allgemeinen Formel I DOLLAR F1 DOLLAR A Aufgabe der Erfindung ist das Erschließen von Substanzklassen, deren Vertreter als Matrix Metalloproteinase-Inhibitoren geeignet sind. Die Aufgabe wird gelöst durch die Herstellung von neuen Pyrimidinverbindungen, die humane MMPs merklich inhibieren. Die Ergebnisse sind tabellarisch dargestellt. Benzo-, cycloalkano- or heterocyclic-fused, 3-(dimercaptoalkyl)-pyrimidine-2,4(1H,3H)-dione derivatives (I) are new. Bicyclic pyrimidinedione derivatives of formula (I) are new. n = 0-2; A = fused benzo ring; 5-7 membered cycloalkyl ring; 5-7 membered cycloheteroalkyl ring containing one O or S; or a heteroaromatic ring containing 1-3 N, O and/or S atoms; R1-R3 = H, halo, 1-6C alkyl, 1-3C alkylthio, 6-12C aryl, NO2, CONH2, 1-4C alkoxy, CN, CF3, NH2, COOH, (1-4C) alkoxycarbonyl, N-(1-4C alkyl)-carbamoyl or 2-5C alkenyl; R4 = H, 1-8C alkyl, 2-5C alkenyl, 2-8C alkynyl, 3-10C cycloalkyl, 3-10C cycloalkenyl, 3-10C cycloalkynyl, -(CH2)a-Z-(1-10C) alkyl, 6-12C aryl or 7-12C aralkyl; a = 1-5; Z = O, S, CO, SO or SO2; and R5 = H or Me; Alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl or cycloalkynyl moieties in R1 - R4 (including the alkyl bonded to Z) are optionally substituted by 1 or 2 of CONH2, OH, 1-4C alkoxy, CN, SO3H, CF3, NH2, COOH, (1-4C) alkoxycarbonyl, N-(1-4C alkyl)-carbamoyl, N,N-di-(1-4C alkyl)-carbamoyl, phenyl, piperazinylcarbonyl or heterocyclyl, the alkyl moieties in which are optionally substituted by 1 or 2 of OH, SO3H, NH2, mono- or di-(1-4C alkyl)-amino or a heterocycle. Independent claims are included for the preparation of (I).