Various substituted isoquinoline-1-carboxaldehyde thiosemicarbazones (12 compounds) have been synthesized and evaluated for antineoplastic activity in mice bearing the L1210 leukemia. Condensation of 4-bromo-1-methylisoquinoline (4) with ammonium hydroxide, methylamine, ethylamine, and N-acetylethylenediamine gave the corresponding 4-amino, 4-methylamino, 4-ethylamino, and 4-N-(acetylethyl)amino derivatives, which were then converted to amides and subsequently oxidized to aldehydes followed by condensation with thiosemicarbazide to yield thiosemicarbazones 8a-c, 9a-c, and 16. Nitration of 4, followed by oxidation with selenium dioxide, produced aldehyde 18, which was then converted to the cyclic ethylene acetal 19. Condensation of 19 with morpholine followed by catalytic reduction of the nitro group and treatment with thiosemicarbazide afforded 5-amino-4-morpholinoisoquinoline-1-carboxaldehyde thiosemicarbazone (22). N-Oxidation of 1,5-dimethylisoquinoline, followed by rearrangement with acetic anhydride, gave, after acid hydrolysis, 1,5-dimethyl-4-hydroxyisoquinoline, which was converted to its acetate and then oxidized to yield 4-acetoxy-5-methylisoquinoline-1-carboxaldehyde (32). Sulfonation of 1,4-dimethylisoquinoline, followed by reaction with potassium hydroxide, acetylation, and oxidation, gave 5-acetoxy-4-methylisoquinoline-1-carboxaldehyde (40). Condensation of compounds 32 and 39 with thiosemicarbazide afforded the respective 4- and 5-acetoxy(5- and 4-methyl)thiosemicarbazones 33 and 40, which were then converted to their respective 4- and 5-hydroxy derivatives 34 and 41 by acid hydrolysis. The most active compounds synthesized were 4-aminoisoquinoline-1-carboxaldehyde thiosemicarbazone (9a) and 4-(methylamino)isoquinoline-1-carboxaldehyde thiosemicarbazone (9b), which both produced optimum % T/C values of 177 against the L1210 leukemia in mice when used at a daily dosage of 40 mg/kg for 6 consecutive days. Furthermore, when 9a was given twice daily at a dosage of 40 mg/kg for 6 consecutive days, a T/C value of 165 was obtained and 60% of the mice were 60-day long-term survivors.

中文翻译：

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异喹啉-1-羧甲醛硫代半脲的4和5取代衍生物的合成及其抗肿瘤活性。

已经合成了各种取代的异喹啉-1-甲醛硫代半脲酮（12种化合物），并评估了患有L1210白血病的小鼠的抗肿瘤活性。4-溴-1-甲基异喹啉（4）与氢氧化铵，甲胺，乙胺和N-乙酰基乙二胺缩合得到相应的4-氨基，4-甲基氨基，4-乙基氨基和4-N-（乙酰乙基）氨基衍生物，然后将其转化为酰胺，然后氧化为醛，然后与硫代氨基甲酰肼缩合，生成硫代半氨基甲酮8a-c，9a-c和16。硝化4，然后用二氧化硒氧化，生成醛18，然后将其转化为醛18环状乙烯缩醛19。用吗啉将19缩合，然后催化还原硝基，并用硫代氨基脲处理，得到5-氨基-4-吗啉代异喹啉-1-羧甲醛硫代氨基脲（22）。N-氧化1,5-二甲基异喹啉，然后用乙酸酐重排，酸水解后得到1,5-二甲基-4-羟基异喹啉，将其转化为乙酸盐，然后氧化得到4-乙酰氧基-5-甲基异喹啉-1-甲醛（32）。磺化1,4-二甲基异喹啉，然后与氢氧化钾反应，乙酰化和氧化，得到5-乙酰氧基-4-甲基异喹啉-1-甲醛（40）。化合物32和39与硫代氨基脲的缩合得到各自的4-和5-乙酰氧基（5-和4-甲基）硫代氨基脲33和40，然后通过酸水解将它们分别转化为它们的4-和5-羟基衍生物34和41。合成的活性最高的化合物是4-氨基异喹啉-1-羧甲醛硫代半碳酸钠（9a）和4-（甲基氨基）异喹啉-1-羧甲醛硫代半碳酰胺（9b），它们均能产生小鼠抗L1210白血病的最佳T / C值为177。连续6天以40 mg / kg的每日剂量使用时。此外，当连续9天以40 mg / kg的剂量每天两次给予9a时，T / C值为165，并且60％的小鼠是60天长期存活者。当连续6天每天以40 mg / kg的剂量使用时，它们在小鼠中产生的针对L1210白血病的最佳％T / C值为177。此外，当连续9天以40 mg / kg的剂量每天两次给予9a时，T / C值为165，并且60％的小鼠是60天长期存活者。当连续6天每天以40 mg / kg的剂量使用时，它们在小鼠中产生的针对L1210白血病的最佳％T / C值为177。此外，当连续9天以40 mg / kg的剂量每天两次给予9a时，T / C值为165，并且60％的小鼠是60天长期存活者。