Piperidine Derivatives of Potential Biological Interest

  • C.J. Rose

Student thesis: Doctoral ThesisDoctor of Philosophy

Abstract

Research involving the structural modification of pethidines and prodines with emphasis on the structure activity relationships has been reviewed.in the hope of obtaining compounds of pharmacological interest, compounds of type (1), where R = alkyl or aralkyl, R1 = H or acyl, R2 = H or C6 H5 and R3 = H or acyl, have been prepared and assessed pharmacologically. The synthetic route adopted consisted of Grignard addition to the corresponding l-substituted 4-cyano-4—piperidone (3), (chemical formula diagram please see thesis) prepared by Thorpe cyclisation of a dinitrile to give an enamine (2) and subsequent hydrolysis. The reaction with Grignard reagents gave a compound which was found to be a tetrahydro-pyridine (4). Possible methods of reduction of the compound were reviewed and the (chemical formula diagram  please see thesis) compound reduced with NaBH4 to give the amino-~alcohol. A second route giving amino-alcohols of type (5, R1 =H) consisted of stepwise reduction of the cyano-ketone (3). The amino-alcohols were capable of existing in stereoisomers, and a study of the stereochemistry led to the provisional assignment of configurations using methods which included hydrolysis and a consideration of the absorption spectra. The amino-alcohols (5) were reacted with aldehydes and ketones to give the cyclic structures (6), where R1 = C6H5 and X = C6H4Y,  0 or S. Y = OH, OCH3, F, NMe2. A consideration of the N.M.R. spectra of these compounds is given. (chemical formula diagram please see thesis) Several of the amino-alcohols and their derivatives were tested for pharmacological activity but the central nervous system activity of these compounds was slight and no useful correlations between activity and structure could be made. Several reactions with the enamine precursor (2) were attempted, which resulted in the preparation of novel tetrahydro-pyridines of the type (7). A consideration of the preparation and properties of these compounds was given. (chemical formula diagram please see thesis) The pharmacological activity of a few of these compounds and their derivatives was investigated, but the compounds were devoid of any significant activity.
Date of AwardAug 1968
Original languageEnglish
Awarding Institution
  • Aston University

Keywords

  • piperidine
  • derivatives
  • biological
  • interest

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