茚满-5-乙酸的抗炎和镇痛非对映体衍生物。

Antiinflammatory and analgesic diastereoisomeric derivatives of indan-5-acetic acid.

作者信息

Teulon J M, Cognacq J C, Hertz F, Lwoff J M, Foulon M, Baert F, Brienne M J, Lacombe L, Jacques J

出版信息

J Med Chem. 1978 Sep;21(9):901-5. doi: 10.1021/jm00207a012.

Abstract

Various 2-alkyl-alpha-methyl- and 2-alkylindan-5-acetic acids have been prepared. The acids, which can exist in two diastereoisomeric forms that cannot be separated by crystallization or chromatography, can be analyzed in their mixture by NMR in the presence of Eu(dpm)3. It has been possible to reconstitute the two pure racemic 2-isopropyl-alpha-methylindan-5-acetic acids from their enantiomers obtained after resolution of the mixtures through salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers salts with various active bases. The relative configuration of the two asymmetric centers of one of the diastereoisomers has been determined by X-ray crystallography. The absolute configurations of the resolved acids have been established by a comparative study of their CD curves. The antiinflammatory and analgesic properties of these compounds as functions of their structure and stereochemistry are discussed.

摘要

已制备了多种2-烷基-α-甲基-和2-烷基茚满-5-乙酸。这些酸以两种非对映异构体形式存在，无法通过结晶或色谱法分离，在Eu(dpm)₃存在下可通过核磁共振对其混合物进行分析。通过与各种活性碱形成盐对混合物进行拆分后得到对映体，进而有可能从这些对映体制备出两种纯的外消旋2-异丙基-α-甲基茚满-5-乙酸。其中一种非对映异构体与各种活性碱形成盐的两个不对称中心的相对构型已通过X射线晶体学确定。通过对拆分后酸的圆二色曲线进行比较研究，确定了其绝对构型。讨论了这些化合物的抗炎和镇痛特性与其结构和立体化学的关系。