SEPARATION OF DRUG STEREOISOMERS BY THE FORMATION OF BETA-CYCLODEXTRIN INCLUSION COMPLEXES
SEPARATION OF DRUG STEREOISOMERS BY THE FORMATION OF BETA-CYCLODEXTRIN INCLUSION COMPLEXES
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DOI：
10.1126/science.3704640
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发表时间：
1986-05-30
期刊：
影响因子：
56.9
通讯作者：
BEESLEY, TE
中科院分区：
文献类型：
--
作者：
ARMSTRONG, DW;WARD, TJ;BEESLEY, TE
对于许多药物，只有外消旋混合物可用于临床。由于不同的药物立体异构体往往引起不同的生理反应，使用纯异构体可以获得更准确的治疗效果。固定化β对多种药物立体异构体的差异络合。研究了-环糊精。手性识别和外消旋分离观察到一些化合物从临床上有用的类，如。β。-阻滞剂、钙通道阻滞剂、镇静催眠药、抗组胺药、抗惊厥药、利尿剂和合成阿片类药物。此外，还分离出了具有心脏活性和抗疟疾作用的金鸡纳生物碱和两种抗雌激素的非对映体。的三维投影。比较了用该方法分离的丙萘洛尔-环糊精配合物和未分离的华法林。这些研究提高了对- β的手性相互作用的认识和应用。-环糊精，他们已经证明了一种测量光学纯度和分离或生产药物的纯对映体的方法。此外，这种高度特异性的技术还可用于对映体药物的药理学评价。
For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized .beta.-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as .beta.-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of .beta.-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of .beta.-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.