Dimmock J R, Sidhu K K, Quail J W, Jia Z, Duffy M J, Reid R S, Kirkpatrick D L, Zhu L, Fletcher S M
College of Pharmacy, University of Saskatchewan, Saskatoon, Canada.
J Pharm Sci. 1992 Nov;81(11):1059-64. doi: 10.1002/jps.2600811103.
Reaction of 2,6-bis-(phenylmethylene)cyclohexanone (1) with a 4-molar excess of hydroxylamine hydrochloride and sodium acetate to produce the corresponding oxime 2 gave rise to 2-(alpha-hydroxyamino-alpha-phenylmethyl)-6-phenylmethylenecyclohexan one oxime (5a), whose structure was deduced from high-resolution proton nuclear magnetic resonance spectroscopy and confirmed by X-ray analysis. Compound 2 was eventually prepared from 1 with hydroxylamine per se and not with a mixture of hydroxylamine hydrochloride and sodium acetate. Ten analogues of 5a, namely 5b-5k, were prepared and evaluated for cytotoxicity. Six of the 11 compounds in series 5, as well as 1, showed activity in the 240-950 microM range against murine mammary EMT6 cells. Series 5 was also examined for cytotoxicity in an in vitro screen conducted by the National Cancer Institute with approximately 54 cell lines, and four compounds demonstrated selective toxicity toward various groups of tumors.
2,6 - 双（苯亚甲基）环己酮（1）与4摩尔过量的盐酸羟胺和醋酸钠反应生成相应的肟2，得到2 - （α - 羟基氨基 - α - 苯甲基） - 6 - 苯亚甲基环己酮肟（5a），其结构通过高分辨率质子核磁共振光谱推导得出，并经X射线分析证实。化合物2最终是由1与羟胺本身反应制备的，而非与盐酸羟胺和醋酸钠的混合物反应制备。制备了5a的10个类似物，即5b - 5k，并对其细胞毒性进行了评估。系列5中的11种化合物中的6种以及1在240 - 950微摩尔范围内对小鼠乳腺EMT6细胞显示出活性。还在美国国立癌症研究所进行的体外筛选中，用大约54种细胞系对系列5进行了细胞毒性检测，有4种化合物对不同肿瘤组显示出选择性毒性。
