Rice K C
J Med Chem. 1976 Jul;19(7):887-92. doi: 10.1021/jm00229a006.
Nine alpha-dibutylaminomethylbenzo[h]quinoline-4-methanols were synthesized from the corresponding 1-amino-naphthalenes by the following sequence: 1-aminonaphthalene leads to 1H-benz[g]indole-2,3-dione leads to benzo[h]quinoline-4-carboxylic acid leads to acid chloride leads to bromomethyl ketone leads to epoxide leads to benzo[h]quinoline-4-methanol. Several acid chlorides substituted in the 3 position reacted incompletely with ethereal diazomethane but were efficiently converted, without isolation of the intermediates, to the bromomethyl ketones by reaction with ethoxymagnesium diethylmalonate, bromination, hydrolysis, and decarboxylation. Several compounds prepared, especially alpha-dibutylaminomethyl-2-(2',4'-dimethylphenyl)-3-methyl-6-chlorobenzo[h]quinoline-4-methanol, showed significant antimalarial activity against Plasmodium berghei in infected mice but were moderately phototoxic.
通过以下步骤从相应的1-氨基萘合成了九种α-二丁基氨基甲基苯并[h]喹啉-4-甲醇：1-氨基萘生成1H-苯并[g]吲哚-2,3-二酮，再生成苯并[h]喹啉-4-羧酸，接着生成酰氯，然后生成溴甲基酮，再生成环氧化物，最后生成苯并[h]喹啉-4-甲醇。几种在3位被取代的酰氯与乙醚重氮甲烷反应不完全，但在不分离中间体的情况下，通过与乙氧基二乙基丙二酸镁反应、溴化、水解和脱羧，有效地转化为溴甲基酮。所制备的几种化合物，特别是α-二丁基氨基甲基-2-(2',4'-二甲基苯基)-3-甲基-6-氯苯并[h]喹啉-4-甲醇，对感染伯氏疟原虫的小鼠显示出显著的抗疟活性，但有中度光毒性。
