Piperidine is among the most important heterocyclic compounds which exhibits most of therapeutic activities due to it's conformationally flexible nature. Molecular modifications of pethidine and morphine like compounds led to the syntheses of new opiates having agonistic as well as antagonistic activities. In many families of opiate narcotic analgesics, small changes in chemical structures have shown to modify the extent to which an analogue exhibits agonist and antagonist activity.
During the course of present work three series of substituted phenacyl and one series of 1-adamantyl methyl ketone, derivatives of 4hydroxypiperidine, 4-hydroxy-4-phenylpiperidine, 4-acetyl-4phenyl piperidine and 2-piperidineethanol were synthesized. The resulting derivatives were screened for analgesic activity by chemical and thermal method. Most of the compounds exhibited analgesic activity when evaluated by chemical method whereas all the compounds proved to be inactive by thermal method.
Halogen substituted phenacyl derivatives among all the series displayed maximum activity in acetic acid induced writhing assay as compared to other substituted derivatives.
Eight derivatives which exhibited maximum percent inhibition of acetic acid induced writhing among their respective series, were selected for studying their effects on brain monoamine levels in male albino mice.
Phenacyl derivatives of 4-hydroxypiperidine, 4-hydroxy-4phenylpiperidine and 4-acetyl-4-phenylpiperidine were also evaluated for their effects on mean arterial blood pressure in normotensive anaesthetized rats and spontaneous contractions of rabbit jejunum. Most of the compounds exhibited hypertensive and hypertensive effects at the dose range of 3-10 mg/kg body weight.
Compound XVII, XXXI and xxxII [l-(2',4'-dimethoxyphenacyl)-4-hydroxy4-phenylpiperidinium bromide, 1-(4' -bromophenacyl)-4-acetyl-4-phenylpiperidinium bromide and 1-(4'-chlorophenacyl)-4-acetyl-4-phenylpiperidinium bromide) were found to be the most potent antihypertensive agents as they caused 84, 88 and 83% fall in blood pressure respectively at the dose of 3 mg/kg and relaxant effects on isolated jejunum at 0.3 mg/kg dose.
Spectroscopic techniques such as 1H-NMR, ElMS, Wand IR were utilized for the characterization and structure confirmation of the compounds.