<p>A series of 3-(3-ethoxypropyl)-7-heterocyclylalkyl-3,7-diazabicyclo[3.3.l]nonan-9-ones have been prepared by Mannich cyclocondensation of 1-(3-ethoxypropyl)-4-oxopiperidine with paraformaldehyde and primary amines followed by Wolff-Kischner reduction of the obtained bispidinones. The starting 1-(3-ethoxypropyl)-4-oxopiperidine was synthesized by Dickmann condensation of 3-ethoxypropylamine with ethylacrylate. The 3,7-diazabicyclo[3.3.1]nonanones were obtained in acceptable yields by condensation of 1-(3-ethoxypropyl)piperidin-4-one with primary amines: 1-(3-aminopropyl)imidazole or 1-(2-aminoethyl) piperazine and formaldehyde in the presence of acetic acid in methanol medium. Reduction of the obtained bispidinones with hydrazine hydrate was carried out in the presence of KOH in triethylene glycol at 160-170 °C for 5 hours. The syntheses were performed under the atmosphere of N<sub>2</sub>. As the reaction products are viscous oils, the column chromatography (on III activity aluminum oxide, eluent – benzene: dioxane 5:1) was used for purification of novel bicyclic ketones and bicyclic nonanes. The completion of the reactions was monitored by TLC. Methods of <sup>1</sup>H and <sup>13</sup>C NMR spectroscopy were used to determine the structures of the substances synthesized. The prior studies have demonstrated that variation on the substituents at nitrogen atoms in 3- and 7-positions of bispidine cycle could result in the increase of biological activity and effect on compound spectral characteristics. Spatial structures of bispidinones and related bispidines were determined on the basis of the data of the <sup>13</sup>C and <sup>1</sup>H NMR spectra. A doublet of doublets of equatorial protons at C<sub>2.4 </sub>and C<sub>6.8</sub> with large geminal constants of 10.5-11 Hz and vicinal constants of 3.0-6.0 Hz in <sup>1</sup>H NMR spectrum revealed that those 3,7-diazabicyclo[3.3.1]nonane derivatives have a “chair-chair” conformation of both piperidine rings.</p>
Objective: Derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one attract considerable attention from pharmacists for the treatment of a wide rangeof diseases. According to this interest, the novel derivatives of 3-cyclopropanmethyl-7-alkoxyalkyl-3,7-diazabicyclo[3.3.1]nonan-9-one withisopropoxypropyl and ethoxypropyl substituents in the position 7 had been synthesized to study their biological activity and toxicity. The practicalsignificance of the work is in the accumulation and development of scientific representations about diazabicyclic compounds, methods for theirsynthesis, structure, and properties, which can subsequently be used in a targeted design and identification of even more complex systems, as wellas in the development of further research in the field of 3,7-diazabicyclo[3.3.1]nonanes. For this purpose, complexes of the synthesized compoundswith β-cyclodextrin are obtained and their biological activity is investigated at the Department of Pharmacology of S.D. Asfendiyarov Kazakh NationalMedical University with the aid of the pharmacological tests.Methods: An experimental study of local anesthetic activity on the models of infiltration, conduction anesthesia, and acute toxicity of synthesizedmolecules was carried out using primary screening methods.Results: As a result of pharmacological screening, it has been found that the compounds exhibit local anesthetic activity and low toxicity and wasrecommended for in-depth study of their pharmacological properties.Conclusion: It turned out that a nature of the N-alkoxyalkyl radical does not affect the toxicity of cyclopropanmethyl- substituted bispidines. In theseries of O-benzoyloximes of bispidinones, the isopropoxypropyl- substituted analog is 1.3 times less toxic than ethoxypropyl- one.
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