Synthesis of Some Potential Analgesic Compounds

Abstract

The main classes of known analgesics, their postulated mechanism of action and methods for their pharmacological evaluation have been briefly reviewed. N-Cycloalkylmethyl derivatives of nor-benzomorphan, nor-morphinan and nor-morphine have been shown to possess interesting analgesic and antagonist properties. All these examples have phenylethylamine moiety and N-cycloalkylmethyl groups in common and this served as a useful starting point for present work. N-Cycloalkylmethyl derivatives of 2-phenylethylamine, tyramine and trans-2-phenylcyclopropylamine were prepared to observe their analgesic properties. The present investigation was also concerned with the preparation of some cocaine and tropane derivatives. 3a-Aminotropane and its derivatives were synthesized. Tropan-3a-ol was N-dealkylated in the hope that the secondary base on alkylation would give compounds with interesting analgesic properties. Attempts were also made to prepare3-benzoyl derivatives of 3-phenyl and 3-methyltropan-3-ols. Attempts to make substituted 2,3-epoxytropan were unsuccessful. The majority of the compounds prepared have been tested for their C.N.S. activity, a selected number of these were also submitted for screening as antibacterial compounds but were found to be devoid of any such activity. Some compounds showed C.N.S. activity but this was not such as to merit further investigation. The range of compounds prepared and their pharmacological effects could not at this stage form the basis of a detailed structure activity relationship.