piperidines and tetrabutylammonium

Synthesis of some novel biologically active piperidin-4-one oxime carbonates from 1-methyl-3alkyl-2,6-diphenylpiperidin-4-one oximes and substituted chloroformates was carried out in the presence of potassium carbonate as base and tetrabutylammonium bromide (TBAB) as catalyst. The newly synthesized compounds were characterized by IR, (1)H, (13)C NMR and LC-mass spectra. Based on the (1)H NMR analysis, all the compounds were found to adopt normal chair conformation with equatorial orientation of all the substituents. For all the synthesized compounds (5a-5l) antimicrobial activity has been tested against bacterial and fungal strains using Streptomycin and Amphotericin B as standards.

Topics: Anti-Infective Agents; Bacteria; Carbonates; Catalysis; Fungi; Magnetic Resonance Spectroscopy; Mass Spectrometry; Microbial Sensitivity Tests; Molecular Conformation; Oximes; Piperidines; Potassium; Quaternary Ammonium Compounds; Stereoisomerism

We have recently proposed that an endocannabinoid is the endothelium-derived hyperpolarizing factor (EDHF) and have now tested this hypothesis in the rat isolated perfused heart. In this preparation bradykinin gave rise to nitric oxide- and prostanoid-independent relaxations, assessed as reductions in coronary perfusion pressure (ED50 = 14.9 +/- 5.9 pmol; Rmax = 25.2 +/- 2.2%), which are thought to be mediated by EDHF. These relaxations were antagonised by both the highly selective cannabinoid antagonist, SR141716A (1 microM) (Rmax = 8.3 +/- 1.2%, P < 0.001) and by the calcium-dependent potassium channel blocker tetrabutylammonium (300 microM) (Rmax = 6.7 +/- 3.4%, P < 0.01) and were abolished by the EDHF inhibitor clotrimazole (3 microM). The endogenous cannabinoid, anandamide, similarly caused coronary vasorelaxation (Rmax = 32.3 +/- 2.3%), which was abolished by clotrimazole (3 microM) and antagonised by both 300 microM tetrabutylammonium (Rmax = 18.2 +/- 2.8%, P < 0.01) and 1 microM SR141716A (Rmax = 16.4 +/- 3.3%, P < 0.01). Accordingly, these results suggest that EDHF-mediated responses in the rat coronary vasculature are due to an endogenous cannabinoid and that anandamide causes vasorelaxation through potassium channel activation. These findings are, therefore, consistent with our recent proposal that EDHF is an endogenous cannabinoid.

Topics: Animals; Arachidonic Acids; Biological Factors; Bradykinin; Calcium Channel Blockers; Cannabinoid Receptor Modulators; Cannabinoids; Clotrimazole; Coronary Vessels; Endocannabinoids; In Vitro Techniques; Male; Muscle, Smooth, Vascular; Piperidines; Polyunsaturated Alkamides; Potassium Channel Blockers; Pyrazoles; Quaternary Ammonium Compounds; Rats; Rats, Wistar; Receptors, Cannabinoid; Receptors, Drug; Rimonabant; Vasodilation