发明名称 10H-benzo[G]pteridine-2,4-dione derivatives, method for the production thereof, and use thereof
摘要 The invention relates to 10H-benzo[g]pteridine-2,4-dione derivatives, to the production thereof, and to the use thereof.
申请公布号 US9241995(B2) 申请公布日期 2016.01.26
申请号 US201214127464 申请日期 2012.06.22
申请人 TRIOPTOTEC GMBH 发明人 Maisch Tim;Späth Andreas
分类号 A61K41/00;A61Q11/00;A61Q11/02;C07D475/14;C11D3/48;A61K8/49 主分类号 A61K41/00
代理机构 Ostrolenk Faber LLP 代理人 Ostrolenk Faber LLP
主权项 1. A compound having the formula (1): where I) only 1 R5 or R6 radical is an organic radical having: a) at least two uncharged, protonatable nitrogen atoms not bonded directly to the isoalloxazine ring, or a) at least two positively charged nitrogen atoms not bonded directly to the isoalloxazine ring, and where each of the R1, R2, R3 and R4 radicals is the same or different and is independently hydrogen, hydroxyl, thiol, nitro, carboxylate, aldehyde having 1 to 20 carbon atoms, ketone having 2 to 20 carbon atoms, O-alkyl having 1 to 20 carbon atoms, S-alkyl having 1 to 20 carbon atoms, O-alkenyl having 2 to 20 carbon atoms, S-alkenyl having 2 to 20 carbon atoms, O-aryl having 5 to 20 carbon atoms, S-aryl having 5 to 20 carbon atoms, carboxylic ester having 1 to 20 carbon atoms, carboxamide having 1 to 20 carbon atoms, thioester having 1 to 20 carbon atoms, alkyl having 1 to 20 carbon atoms, alkenyl having 2 to 20 carbon atoms, cycloalkyl having 3 to 20 carbon atoms, cycloalkenyl having 3 to 20 carbon atoms, aryl having 5 to 20 carbon atoms or heteroaryl having 4 to 20 carbon atoms, which does not contain any nitrogen atoms, and where each of the R5 and R6 radicals which is not an organic radical having a) at least two uncharged, protonatable nitrogen atoms not bonded directly to the isoalloxazine ring, or b) at least two positively charged nitrogen atoms not bonded directly to the isoalloxazine ring, is the same or different and is independently hydrogen, alkyl having 1 to 20 carbon atoms, alkenyl having 2 to 20 carbon atoms, cycloalkyl having 3 to 20 carbon atoms, cycloalkenyl having 3 to 20 carbon atoms, aryl having 5 to 20 carbon atoms or heteroaryl having 4 to 20 carbon atoms, which does not contain any nitrogen atoms, or wherein R5 can be acyclic polyol radical selected from the group consisting of arabityl, ribityl, xylityl, erythrityl, threityl, lactityl, mannityl and sorbityl, or an ether, ester or acetal thereof with the proviso that compounds are excluded in which the R1, R4 and R6 radicals are hydrogen, the R2 radical is hydrogen, alkyl having 1 to 8 carbon atoms or cycloalkyl having 3 to 7 carbon atoms, the R3 radical is hydrogen, halogen, alkyl having 1 to 8 carbon atoms, O-alkyl having 1 to 8 carbon atoms or a heterocyclic radical having 4 to 7 carbon atoms, and the R5 radical is an alkyl radical which has 1 to 8 carbon atoms and is substituted by at least by a radical of the formula —N(R35)(R36) or a radical of the formula —OR35, where the R35 radical is a radical of the formula —C1-8 alkyl(amine)-OR37 or a 7,8-dimethylisoalloxazin-10-yl-C1-8alkyl radical and where the R36 radical is hydrogen or a radical of the formula —C1-8alkyl, which may be unsubstituted or substituted, and where the R37 radical is hydrogen, aryl having 6 to 7 carbon atoms or alkyl which may be unsubstituted or substituted and has 1 to 8 carbon atoms, and additionally excluding compounds in which the R1 and R4 radicals are hydrogen , the R6 radical is hydrogen or a radical having the general formula —C1-4alkyl-OC(O)CH3, the R2 radical is hydrogen or alkyl having 1 to 8 carbon atoms and the R5 radical is a radical having the general formula —C1-6alkyl-N(R31)—C0-3alkyl-(R32), where R31 is hydrogen or a radical having the formula —C1-4alkyl and where R32 is a radical having the formula —C1-4alkyl-N(R33)(R34), a radical having the formula —C0-4alkyl-aryl, a radical having the formula —C0-4 alkylheterocycloalkyl or a radical having the formula —C0-4alkylheteroaryl, and where the R33 and R34 radicals are each independently hydrogen or -C1-4alkyl, and excluding 10-butyl-7,8-dimethyl-3-[2-oxo-2-(1,4,7,10-tetrazacyclododec-1-yl)ethyl]benzo[g]pteridine-2,4-dione and 10-[2-(2-methoxyethoxy)ethyl]-7,8-dimethyl-3-[2-oxo-2-(1,4,7,10-tetrazacyclododec-1-y1)ethyl]benzo[g]pteridine-2,4-dione, or where II) only 1 R5 or R6 radical is an organic radical having: a) at least one uncharged, protonatable nitrogen atom not bonded directly to the isoalloxazine ring, and b) at least one positively charged nitrogen atom not bonded directly to the isoalloxazine ring, and where each of the R1, R2, R3 and R4 radicals is the same or different and is independently hydrogen, hydroxyl, thiol, nitro, carboxylate, aldehyde having 1 to 20 carbon atoms, ketone having 2 to 20 carbon atoms, O-alkyl having 1 to 20 carbon atoms, S-alkyl having 1 to 20 carbon atoms, O-alkenyl having 2 to 20 carbon atoms, S-alkenyl having 2 to 20 carbon atoms, O-aryl having 5 to 20 carbon atoms, S-aryl having 5 to 20 carbon atoms, carboxylic ester having 1 to 20 carbon atoms, carboxamide having 1 to 20 carbon atoms, thioester having 1 to 20 carbon atoms, alkyl having 1 to 20 carbon atoms, alkenyl having 2 to 20 carbon atoms, cycloalkyl having 3 to 20 carbon atoms, cycloalkenyl having 3 to 20 carbon atoms, aryl having 5 to 20 carbon atoms or heteroaryl having 4 to 20 carbon atoms, which does not contain any nitrogen atoms, or where each of the R5 and R6 radicals which is not an organic radical having a) at least one uncharged, protonatable nitrogen atom not bonded directly to the isoalloxazine ring, or b) at least one positively charged nitrogen atom not bonded directly to the isoalloxazine ring, is the same or different and is independently hydrogen, alkyl having 1 to 20 carbon atoms, alkenyl having 2 to 20 carbon atoms, cycloalkyl having 3 to 20 carbon atoms, cycloalkenyl having 3 to 20 carbon atoms, aryl having 5 to 20 carbon atoms or heteroaryl having 4 to 20 carbon atoms, which does not contain any nitrogen atoms or wherein R5 can be acyclic polyol radical selected from the group consisting of arabityl, ribityl, xylityl, erythrityl, threityl, lactityl, mannityl and sorbityl, or an ether, ester or acetal thereof, or where III) R5 and R6 radicals are an organic radical having at least one selected from the group consisting of: a) at least one uncharged, protonatable nitrogen atom not bonded directly to the isoalloxazine ring, and b) at least one positively charged nitrogen atom not bonded directly to the isoalloxazine ring, and where each of the R1, R2, R3 and R4 radicals is the same or different and is independently hydrogen, hydroxyl, thiol, nitro, carboxylate, aldehyde having 1 to 20 carbon atoms, ketone having 2 to 20 carbon atoms, O-alkyl having 1 to 20 carbon atoms, S-alkyl having 1 to 20 carbon atoms, O-alkenyl having 2 to 20 carbon atoms, S-alkenyl having 2 to 20 carbon atoms, O-aryl having 5 to 20 carbon atoms, S-aryl having 5 to 20 carbon atoms, carboxylic ester having 1 to 20 carbon atoms, carboxamide having 1 to 20 carbon atoms, thioester having 1 to 20 carbon atoms, alkyl having 1 to 20 carbon atoms, alkenyl having 2 to 20 carbon atoms, cycloalkyl having 3 to 20 carbon atoms, cycloalkenyl having 3 to 20 carbon atoms, aryl having 5 to 20 carbon atoms or heteroaryl having 4 to 20 carbon atoms, which does not contain any nitrogen atoms, and and wherein the compound having the formula (20) is excluded: and wherein in variants I), II) and III) of the compound of formula (1), the alkyl radicals and alkenyl radicals may be straight-chain or branched and be either unsubstituted or substituted by at least one radical selected from the group consisting of hydroxyl, sulfanyl, alkyloxy, alkylsulfanyl, alkanoyloxy, amino, alkylamino having 1 to 4 carbon atoms, dialkylamino having 2 to 8 carbon atoms, trialkylammonio having 3 to 12 carbon atoms, and guanidino.
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