Chou J T, Beck W T, Khwaja T, Mayer K, Lien E
J Pharm Sci. 1977 Nov;66(11):1556-61. doi: 10.1002/jps.2600661114.
To overcome the disadvantages of hydroxyurea in anticancer therapy such as fast biotransformation and low potency, five cyclic N-hydroxyureas were synthesized. A new reaction was developed to prepare the desired products from the appropriate alkyl omega-haloalkylcarbamates with hydroxylamine. This reaction probably involves a two-step mechanism: nucleophilic substitution and intramolecular cyclization. The anticancer screening tests of these compounds were done both in vitro using tissue culture and in vivo. One compound, 1-hydroxy-1,3-diazacylohexan-2-one, had anticancer activity comparable to hydroxyurea both in vivo and in vitro.
为克服羟基脲在抗癌治疗中的缺点，如快速生物转化和低效力，合成了五种环状N-羟基脲。开发了一种新反应，由合适的ω-卤代烷基氨基甲酸酯与羟胺制备所需产物。该反应可能涉及两步机理：亲核取代和分子内环化。这些化合物的抗癌筛选试验在体外利用组织培养进行，也在体内进行。一种化合物，1-羟基-1,3-二氮杂环己烷-2-酮，在体内和体外均具有与羟基脲相当的抗癌活性。
