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

• Published in: Journal of medicinal chemistry 1978-09, Vol.21 (9), p.901-905
• Main Authors: Teulon, J. M, Cognacq, J. C, Hertz, F, Lwoff, J. M, Foulon, M, Baert, F, Brienne, M. J, Lacombe, L, Jacques, J
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Crystallization; Indans - chemical synthesis; Indans - isolation & purification; Indans - pharmacology; Indenes - chemical synthesis; Models, Molecular; Molecular Conformation; Rats; Stereoisomerism; Structure-Activity Relationship
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00207a012

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.