Some Substituted Piperidines of Potential Biological Interest

  • Judith Kay Lowe

Student thesis: Master's ThesisMaster of Science (by Research)


Recent investigations have shown that what appears to be comparatively minor chemical modifications of some classical narcotic analgesics can bring about profound changes in their biological activity. Piperidine-based analgesics such as pethidine and the prodines have formed a particularly useful starting point for such investigations: these have been briefly reviewed.
In prodine-type analgesics, marked changes in biological effect, mainly of a quantitative nature but also to some extent qualitatively, can be achieved by variation of the substituent in the three position. The effect of such substituents on the biological activity of some piperidines has been investigated in the present work. A number of 4-hydroxypiperidines of the following type have been prepared:
***please refer to thesis to see the diagram***
The synthesis of these compounds involved the preparation of piperidines with a ketone group in the three position; these ketones have been prepared by cyclizing Mannich bases with a primary amine. The ketones gave oximes which were converted to the corresponding primary amines, thus giving a series of novel compounds for biological assessment. The side chain amino group was capable of acylation and alkylation, thus allowing the effect of changes in the side chain to be investigated.
The present work was concerned largely with compounds based on N-benzyl piperidine. This N substituent was chosen in the hope that its removal might give a centric base piperidine which, on alkylation, would lead to a greater variety of substituents on the ring nitrogen. A limited number of tetrahydropyridines derived from the corresponding 4-hydroxypiperidines have been synthesized.
Most of the compounds prepared in the present work have been screened for smooth muscle, C.N.S., cardiovascular, and antibacterial activity. All compounds tested were devoid of significant smooth muscle and antibacterial activity. Some showed C.N.S. activity, but this was not such as to merit further investigation. Several compounds had a marked effect in lowering the blood pressure, but further evaluation suggested this was usually achieved by a clinically unacceptable mechanism.
The range of compounds prepared and their pharmacological effects could not at this stage form the basis of a detailed discussion of structure-activity relationships
Date of Award1968
Original languageEnglish


  • pharmacy
  • piperidines
  • biological interest

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