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.
(1). J. Salaün, Rearrangements involving the cyclopropyl group. In: Z. Rappoport (Eds.) The Chemistry of the Cyclopropyl Group. Volume 1, Wiley & Sons: New York 1987. p. 809–876.
(2). de Meijere, L. Wessjohann, Synlett 1 (1990). 20–32. Crossref
(3). J. Salaün, Cyclopropane Derivatives and their Diverse Biological Activities. In: A. de Meijere (Eds.) Small Ring Compounds in Organic Synthesis VI. Topics in Current Chemistry, 207 (2000) 1–67. Crossref
(4). A.V. Symon, N.N. Veselova, A.P. Kaplun, N.K. Vlasenkova, G.A. Fedorova, A.I. Liutik, G.K. Gerasimova, VI. Shvrts, Russ. J. Bioorg. Chem. (2005) 286–291. Crossref
(5). L.A. Wessjohann, W. Brandt, Chem. Rev. 103 (2003) 1625–1647. Crossref
(6). N.T. Pokhodylo, V.S. Matiichuk, N.D. Obushak. Russ. J. Bioorg. Chem. 46 (2010) 894–897. Crossref
(7). M. Marradi, A. Brandi, J. Magull, H. Schill, A. de Meijere, Eur. J. Org. Chem. 24 (2006) 5485–5494. Crossref
(8). Zanobini, A. Brandi, A. de Meijere. Eur. J. Org. Chem. 5 (2006) 1251–1255. Crossref
(9). P.M. Weintraub, J.S. Sabol, J.M. Kane, D.R. Borcherding, Tetrahedron 59 (2003) 2953–2989. Crossref
(10). G.G. Furin. Fluorine-containing heterocyclic compounds. Synthesis and application. Novosibirsk: Nauka, 2001, 304 p. (in Russian).
(11). R. Filler, Y. Kobayashi, Biomedicinal Aspects of Fluorine Chemistry; Kodansha Ltd.: Tokyo, Elsevier Biomedical Press: Amsterdam, 1982.
(12). Yu.A. Fialkov, L.M. Yagupolsky, Physiologically active substances [Fiziologicheski aktivnye veshhestva] 14 (1982) 3–22 (in Russian).
(13). L.M. Yagupolsky, A.G. Fadeicheva, G.I. Matyushecheva, E.S. Endelman, Journal of General Chemistry [Zhurnal obshhej himii] 37 (1967) 2787–2788 (in Russian).
(14). B. Granger, S. Albu, Ann. Clin.Psychiatry 17 (2005) 137–140. Crossref
(15). L.M. Yagupolsky, Aromatic and heterocyclic compounds with fluorine containing substituents, Kiev: Naukova Dumka, 1988, 320 p. (in Russian.)
(16). N. Choudhary, U. Gupta, O.D. Gupta, Int. J. ChemTech Res. 6 (2014) 5687–5691.
(17). K.D. Praliyev. C- and N-substituted mono and bicyclic piperidines: synthesis, stereochemistry, transformations and properties, new synthetic analgetics and anaesthetics. Chemistry and biological activity of synthetic and natural compounds. Nitrogen heterocycles and alkaloids. (Eds. V.G. Karcev, G.A. Tolstikov), M: Iridium-Press, 1 (2001) 130–138 (in Russian).
(18). V.K. Yu, K.D. Praliyev, E.E. Fomicheva, S.N. Shin, News of the Korean Scientific and Technical Society “KAXAK” [Izvestija Korejskogo nauchno-tehnicheskogo obshhestva “KAHAK”] 1 (1998) 91–97 (in Russian).
(19). V.K. Yu, T.A. Salita, M.V. Korablev, N.M. Kurbat, Biologically active substances [Biologicheski aktivnye veshhestva] Part 1 (1989) 79–88 (in Russian).
(20). Author’s certificate of the USSR № 1596707. 1-(2-ethoxyethyl)-4-propionyloxy-piperidine hydrochloride possessing a local anaesthetic activity (MAB-32). K.D. Praliyev, V.K. Yu, H.M. Kurbat et al. Published 01.06.90.
(21). Predpatent of RK №3187. 1-(3-n.-butoxypropyl)-4-propionyloxy-piperidine hydrochloride possessing a local anaesthetic activity and semiproduct of its preparation. V.K. Yu, E.E. Fomicheva, K.D. Praliyev, S.N. Shin et al. Published 15.03.96. Bull №1.
(22). A.K. Amantaeva, K.D. Praliyev, V.K. Yu, S.Zh. Praliyev, G.S. Akhmetova, Chemical Journal of Kazakhstan [Himicheskij zhurnal Kazahstana] 2 (2005) 134–140 (in Russian).
(23). K.D. Praliyev, V.K. Yu, I.A. Poplavskaya. Directed synthesis of new pharmacologically active substances in the series of 4-ethynyl-4-hydroxypiperidine derivatives. Chemistry and biological activity of synthetic and natural compounds. Nitrogen heterocycles and alkaloids. (Eds. V.G. Karcev, G.A. Tolstikov), M: Iridium-Press, 1 (2001) 484–489 (in Russian).
(24). G.M. Pichkhadze, G.S. Smagulova, D.M. Kadyrova, K.D. Praliev, V.K. Yu, Pharm. Chem. J. 50 (2016) 600–602. Crossref
(25). R.A. Sharipov, K.S. Sharapov, U.S. Kemelbekov, V.A. Volynkin, J. Incl. Phenom. Macro. 87 (2017) 141–148. Crossref
(26). F.M. Sadyrbayeva, G.S. Akhmetova, K.D. Praliyev, H. Osman, N.V. Korotetskaya, Eurasian Chem. Techn. J. 19 (2017) 183–190. Crossref
(27). Patent of RF №1704415. 1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine possessing a local anaesthetic activity (cascaine). Praliyev K.D., Issin K.D., Issin Zh.I., et al. Published 08.07.96.
(28). Patent of RF №1746667. 1-(2-ethoxyethyl)-4-ethynyl-4-oxypiperidine as an intermediate compound in the synthesis of 1-(2-ethoxyethyl)-4-ethynyl-4-acyloxypiperidines possessing a local anaesthetic activity (CASCAINE semiproduct) K.D. Praliyev, Zh.I. Issin, V.K.Yuet al. Published 08.07.96.
(29). Guide on the conduct preclinical studies drugs, Part 1, M: Grif and K, 2012, 944 p. (in Russian).
(30). Authorʼs certificate of USSR №1220298. 1,2,5-trimethylpiperidone-4 o-benzoyloxime hydrochloride possessing an antagonistic activity in relation to morphine, promedol and ethanol. L.M. Sharkova, L.M. Andronova, V.A. Zagorevsky, N.K. Barkov.
(31). A.K. Amantaeva, G.S. Akhmetova, V.K. Yu, K.D. Praliyev, S.N. Shin, Bulletin of the National Academy of Sciences of the Republic of Kazakhstan (chemical series) [Vestnik nacional’noj akademii nauk (serija himicheskaja)] 4 (2004) 86–91 (in Russian).
(32). K.D. Praliyev, V.K. Yu, G.S. G.S. Akhmetova, Bulletin of the National Academy of Sciences of the Republic of Kazakhstan (chemical series) [Vestnik nacional’noj akademii nauk (serija himicheskaja)] 1 (2000) 96–101 (in Russian).
(33). G.S. Akhmetova, F.M. Sadyrbaeva, V.K. Yu, K.D. Praliyev, O.T. Zhilkibaev, G.M. Pichkhadze, S.R. Nassyrova, Sh.O. Imashova, M.K. Amirkulova, Chemical Journal of Kazakhstan [Himicheskij zhurnal Kazahstana] 1 (2012) 118–127 (in Russian).
(34). K.D. Praliyev, V.K. Yu, Chemical Journal of Kazakhstan [Himicheskij zhurnal Kazahstana] 4 (2005) 186–207 (in Russian).
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