Synthesis and Myelostimulatory Activity of 1-(2-Ethoxyethyl) Piperidine Derivatives

This study concerns the synthesis of 1-(2-ethoxyethyl)-4-oktynyl-4-hydroxypiperidine derivatives. The condensation of 1-(2-ethoxyethyl)-4-oxopiperidine with 1-oktyne by modified Favorskii reaction gave 1-(2-ethoxyethyl)-4-oktynyl-4-hydroxypiperidine. The structure of 4-alkynylpiperid-4-ol is in a good agreement with the results of elemental analysis and IR and 13C NMR spectral data. Acylation of hydroxyl group of obtained alcohol led to corresponding esters. To carry out the preliminary pharmacological study and to obtain the solid forms of new potentially biologically active piperidine derivatives their β-cyclodextrin complexes with β-cyclodextrin have been synthesized. The pharmacological activities of new compounds were predicted by PASS computer program. It has been found that 1-(2-ethoxyethyl)-4-oktynyl-4-acyloxypiperidines can exhibit anesthetic, anesthetic local, spasmolytic and immunosuppressory effects. The preliminary study of 1-(2-ethoxyethyl)-4-(oktyn-1-yl)-4-propionyloxypiperidine (BIV-71) and 1-(2-ethoxyethyl)-4-(oktyn-1-yl)-4-benzoyloxypiperidine (BIV-81) activities were carried out. It was shown that esters complexes possess a higher myelostimulatory activities compared with levamisole as standard. The acute toxicity of the β-cyclodextrin complexes is smaller than levamisole ones.