The Search for Biologically Active Compounds in the Series of N-ethoxyethylpiperidine Derivatives

With the aim to introduce fragment of cyclopropane and fragments of p-, m-, o-fluorophenyls into the structures of N-ethoxyethylpiperidines, acylation of oxime and phenylacetylenic alcohol of 1-(2-ethoxyethyl)-4-ketopiperidine by cyclopropanecarbonylchloride was carried out; on the basis of 1-(2-ethoxyethyl)-4-ethynyl-4-hydroxypiperidine (cascaine alcohol), acylation by 4-fluoro-, 3-fluoro-, 2-fluorobenzoylchlorides was carried out with formation of the corresponding piperidine containing hydrochlorides of cyclopropanecarboxylic acid esters and para-, meta-, ortho-fluorobenzoic esters. Acylation reaction on the hydroxyl group of compounds is carried out in absolute dioxane, the acylating agents are cyclopropanecarbonylchloride, p-, m-, o-fluorobenzoyl chlorides taken in excess. The obtained esters of cyclopropanecarboxylic and para-, meta-, ortho-fluorobenzoic acids are crystalline substances with a clear melting point, well soluble in water, ethanol, acetone. P-fluorobenzoates are obtained with better yields, m-fluorobenzoates occupy an intermediate position, and o-fluorobenzoates are formed with the lowest yields. The best yields of fluorobenzoates are obtained using dioxane as a solvent. Para-, meta-, ortho-fluorobenzoic esters of 1-(2-ethoxyethyl)-4-ethynyl-4-hydroxypiperidine coded A-4 – A-6 were studied for the presence of antimicrobial activity, the actions of these preparations were evaluated in vitro in relation to strains of gram-positive bacteria Staphylococcus aureus, Bacillus subtilis, gram-negative strains of Escheriсhia coli, Pseudomonas aeruginosa and to yeast fungus Сandida albicans by the diffusion method into agar (holes). Introduction of fluorine atom into the structure of cascaine lead to manifestation of antimicrobial activity.

New Anti-Infective Preparations of Naphthyloxypropargylpiperidine Series

1-alkyl-4-(3-naphthyloxyprop-1-ynyl)piperidine-4-ols have been obtained by the condensation of 1-alkyl-pipieridin-4-ones with 1- and 2-naphthoxypropines by the Favorsky method in absolute diethylether, in the presence of powered technical KОН, under atmospheric pressure. Acylation of tertiary naphthoxypropynyl piperidols by cyclopropanecarbonylchloride has been carried out in order to introduce a cyclopropanecarbonyl fragment into the structures of naphthoxypropargylpiperidines. The obtained esters of cyclopropanecarboxylic acid represent crystalline substances with the definite melting temperature, very soluble in water, ethanol, acetone. The composition and structure of the synthesized compounds have been confirmed by the data of elemental analysis, IR-spectroscopy, NMR-spectroscopy, the identity has been confirmed by thin-layer chromatography. The compounds under the code AIP (anti-infective preparation) have been studied for an antimicrobial activity in relation to museum microbial strains. The effects of these preparations have been assessed in vitro in relation to Bacillus subtilis ATCC 6633, Escherichia coli ATCC 25922, Salmonella enterica ATCC 14028 and Staphylococcus aureus ATCC 6538- P. It has been found that the compounds AIP-30 and AIP-31 possess an antimicrobial activity in relation to all strains of microorganisms, engaged in the experiment. AIP- 30 and AIP-31 have antimicrobial effects to different extents, AIP-30 has displayed the highest activity in relation to the museum strain Bacillus subtilis ATCC 6633 in the concentration of 250 μg/ml. It has been established that AIP-32 displays a selective antimicrobial activity towards one type, and AIP-33 ‒ towards two types of the museum strains, engaged in the experiment.