BROWN B T, STAFFORD A, WRIGHT S E
Br J Pharmacol Chemother. 1962 Apr;18(2):311-24. doi: 10.1111/j.1476-5381.1962.tb01411.x.
A series of derivatives of digitoxigenin and digoxigenin were prepared and tested for toxicity in the cat and the guinea-pig and on the isolated heart of the 48-hr chick embryo, and for inotropic activity on the cat isolated papillary muscle and the guinea-pig Langendorff heart. The order of relative potency of the compounds remained the same whether they were tested for toxicity or for positive inotropic activity. There are three molecular centres in the cardiac aglycone that are linked closely with cardiac activity. These are: (a) an OH at carbon-3 which can be combined as a glycoside, thus enhancing activity, or esterified or oxidized, producing compounds of lower activity; the maximum intensity of the inotropic response was reduced in the less potent compounds; (b) a 14-beta-OH associated with a cis C-D ring junction, alteration of which abolished activity; (c) an unsaturated cyclobutenolide ring which cannot be reduced without a great decrease in activity.
制备了一系列洋地黄毒苷元和地高辛苷元的衍生物，并在猫和豚鼠身上以及48小时鸡胚的离体心脏上测试了它们的毒性，还在猫离体乳头肌和豚鼠Langendorff心脏上测试了它们的正性肌力活性。无论测试化合物的毒性还是正性肌力活性，其相对效力顺序都保持不变。强心苷配基中有三个分子中心与心脏活性密切相关。它们是：(a) 碳-3位的一个羟基，它可以作为糖苷结合，从而增强活性，或者酯化或氧化，生成活性较低的化合物；效力较低的化合物中，正性肌力反应的最大强度降低；(b) 与顺式C-D环连接相关的14-β-羟基，其改变会使活性丧失；(c) 一个不饱和环丁烯内酯环，若不使其活性大幅降低就不能还原。
