{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T12:54:46Z","timestamp":1769604886866,"version":"3.49.0"},"reference-count":35,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Committee of Science of the Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["BR27101179"],"award-info":[{"award-number":["BR27101179"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Cyanohydrin synthesis, as the simplest preparative method for introducing a carboxyl group into a piperidine molecule, has been used to obtain potentially biologically active piperidinecarboxylic acids, which have alkyl and arylalkyl radicals at the nitrogen atom of the piperidine ring. Hydrochlorides of cyclopropanecarboxylic acid esters based on piperidinecarboxylic acids, as well as hydrochlorides of fluorobenzoic acid esters of N-substituted piperidines, have been synthesized. The purpose of this study was to search for antiviral drugs among new piperidine derivatives. The structure of the synthesized compounds was studied by NMR methods, including COSY (1H-1H), HMQC (1H-13C) and HMBC (1H-13C) techniques. The values of chemical shifts, multiplicities, and integrated intensities of 1H and 13C signals in one-dimensional NMR spectra were determined. The results of COSY (1H-1H), HMQC (1H-13C), and HMBC (1H-13C) revealed homo- and heteronuclear interactions, confirming the structure of the studied compounds. The antiviral and cytotoxic activities of the synthesized compounds were studied. The antiviral activity in vitro was determined according to the therapeutic regimen against the influenza A\/Swine\/Iowa\/30 (H1N1) virus on the MDCK cell model. The cytotoxicity of the studied substances in vitro was assessed using the MTT test. Based on the results of the antiviral activity against the influenza A virus, it can be concluded that all substances are effective against the influenza A\/H1N1 virus compared to the commercial preparations Tamiflu and Rimantadine.<\/jats:p>","DOI":"10.3390\/molecules30122540","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T09:59:14Z","timestamp":1749549554000},"page":"2540","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Search for Antiviral Preparations in Series of New Derivatives of N-Substituted Piperidines"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9074-1464","authenticated-orcid":false,"given":"Gulmira S.","family":"Akhmetova","sequence":"first","affiliation":[{"name":"Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ulzhalgas B.","family":"Issayeva","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaldybay D.","family":"Praliyev","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0397-7840","authenticated-orcid":false,"given":"Ilya S.","family":"Korotetskiy","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"},{"name":"International Engineering and Technological University LLC, Almaty 050060, Kazakhstan"},{"name":"Research and Production Association Kazpharmacom LLC, Irgeli 040900, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0079-4755","authenticated-orcid":false,"given":"Tulegen M.","family":"Seilkhanov","sequence":"additional","affiliation":[{"name":"The Laboratory of Engineering Profile of NMR Spectroscopy, Sh. Ualikhanov Kokshetau State University, Kokshetau 020000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3807-1299","authenticated-orcid":false,"given":"Samir A.","family":"Ross","sequence":"additional","affiliation":[{"name":"National Center for Natural Products Research, School of Pharmacy, The University of Mississippi, Oxford, MS 38677, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2665-178X","authenticated-orcid":false,"given":"Manas T.","family":"Omyrzakov","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ubaidilla M.","family":"Datkhayev","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Khaidar S.","family":"Tassibekov","sequence":"additional","affiliation":[{"name":"Laboratory of Synthetic and Natural Medicinal Compounds Chemistry, A.B. Bekturov Institute of Chemical Sciences JSC, 106 Sh. Ualikhanov St., Almaty 050010, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7194-0556","authenticated-orcid":false,"given":"Lyudmila N.","family":"Ivanova","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalya V.","family":"Zubenko","sequence":"additional","affiliation":[{"name":"Scientific Center for Anti-Infectious Drugs JSC, Almaty 050060, Kazakhstan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1097\/01.SMJ.0000084984.13843.C0","article-title":"Complications of influenza","volume":"96","author":"Khater","year":"2003","journal-title":"South Med. J."},{"key":"ref_2","first-page":"216","article-title":"Influenza virus pneumonia: Pathogenesis, treatment, and prevention","volume":"10","author":"Piedra","year":"1995","journal-title":"Semin. Respir. Infect."},{"key":"ref_3","first-page":"1627","article-title":"Influenza","volume":"393","author":"Paules","year":"2019","journal-title":"Lancet"},{"key":"ref_4","first-page":"1375","article-title":"Influenza complications in children","volume":"70","author":"Widmer","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_5","first-page":"2006","article-title":"Lessons from Influenza Pandemics of the 20th Century","volume":"72","author":"Monto","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.2105\/AJPH.2012.301137","article-title":"The Burden of Influenza B: A Structured Literature Review","volume":"103","author":"Glezen","year":"2020","journal-title":"Am. J. Public Health"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8502","DOI":"10.1128\/JVI.74.18.8502-8512.2000","article-title":"Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hem agglutinins after their introduction into mammals","volume":"74","author":"Matrosovich","year":"2000","journal-title":"J. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1097\/01.SMJ.0000084986.13843.52","article-title":"Viral characteristics of influenza","volume":"96","author":"Moorman","year":"2003","journal-title":"South Med. J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1016\/j.jmb.2005.11.002","article-title":"Glycan microarray analysis at the hemagglutinins from modern and pandemic influenza viruses reveals different receptor specificities","volume":"355","author":"Stevens","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_10","first-page":"19124","article-title":"A human case of swine influenza virus infection in Eurupe\u2014Implications for human health and research","volume":"14","author":"Van","year":"2009","journal-title":"Euro Surveill."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1086\/512813","article-title":"Cases at swine influenza in humans: Review at the literature","volume":"44","author":"Myers","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.3201\/eid1312.061323","article-title":"Swine workers and swine influenza virus infections","volume":"13","author":"Gray","year":"2007","journal-title":"Emerg. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/S1359-6446(98)01241-0","article-title":"Targeting influenza virus neuraminidase\u2014A new strategy for antiviral therapy","volume":"3","author":"Oxford","year":"1998","journal-title":"Drug Discov. Today"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/(SICI)1099-1654(200003\/04)10:2<119::AID-RMV272>3.0.CO;2-O","article-title":"Influenza A pandemics at the 20th century with special reference to 1918: Virology, pathology and epidemiology","volume":"10","author":"Oxford","year":"2000","journal-title":"Rev. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.3201\/eid1109.041344","article-title":"Potential impact of antiviral drug use during influenza pandemic","volume":"11","author":"Gani","year":"2005","journal-title":"Emerg. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2953","DOI":"10.1016\/S0040-4020(03)00295-3","article-title":"Recent advances in the synthesis of piperidones and piperidines","volume":"59","author":"Weintraub","year":"2003","journal-title":"Tetrahedron"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1007\/s11094-016-1498-7","article-title":"Local Anesthetic Activity of a Promising Piperidine Derivative (LAS-54) in Combination with Epinephrine","volume":"50","author":"Pichkhadze","year":"2016","journal-title":"Pharm. Chem. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"183","DOI":"10.18321\/ectj650","article-title":"New Anti-Infective Preparations of Naphthyloxypropargylpiperidine Series","volume":"19","author":"Sadyrbayeva","year":"2017","journal-title":"Eurasian Chem.-Technol. J."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zolotareva, D., Zazybin, A., Dauletbakov, A., Belyankova, Y., Giner, B., Tursynbek, S., Seilkhanov, T., and Kairullinova, A. (2024). Morpholine, Piperazine, and Piperidine Derivatives as Antidiabetic Agents. Molecules, 29.","DOI":"10.3390\/molecules29133043"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Frolov, N.A., and Vereshchagin, A. (2023). Piperidine Derivatives: Recent Advances in Synthesis and Pharmacological Applications. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032937"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s43094-021-00335-y","article-title":"Piperidine Nucleus in the Field of Drug Discovery","volume":"7","author":"Abdelshaheed","year":"2021","journal-title":"Future J. Pharm. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1080\/00397911.2020.1776876","article-title":"Synthesis, Identification and Molecular Docking Studies of N-Functionalized Piperidine Derivatives Linked to 1,2,3-Triazole Ring","volume":"50","author":"Dawood","year":"2020","journal-title":"Synth. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6141","DOI":"10.1002\/chem.202001355","article-title":"Understanding the Conformational Behavior of Fluorinated Piperidines: The Origin of the Axial-F Preference","volume":"26","author":"Nairoukh","year":"2020","journal-title":"Chem. Eur. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"12052","DOI":"10.1021\/acscatal.0c03278","article-title":"Accessing (Multi)Fluorinated Piperidines Using Heterogeneous Hydrogenation","volume":"10","author":"Wagener","year":"2020","journal-title":"ACS Catal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.1021\/acs.joc.4c00143","article-title":"Synthesis and Chemoinformatic Analysis of Fluorinated Piperidines as 3D Fragments for Fragment-Based Drug Discovery","volume":"89","author":"Renault","year":"2024","journal-title":"J. Org. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8315","DOI":"10.1021\/acs.jmedchem.5b00258","article-title":"Applications of Fluorine in Medicinal Chemistry","volume":"58","author":"Gillis","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e202300937","DOI":"10.1002\/ejoc.202300937","article-title":"Gem-Difluoro-3-azabicyclo [3.n.1]alkanes and Their Derivatives\u2014Bicyclic Fluorinated Piperidine Isosteres for Drug Discovery","volume":"27","author":"Kihakh","year":"2023","journal-title":"Eur. J. Org. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rizzo, C., Amata, S., Pibiri, I., Pace, A., Buscemi, S., and Palumbo Piccionello, A. (2023). FDA-Approved Fluorinated Heterocyclic Drugs from 2016 to 2022. Molecules, 28.","DOI":"10.3390\/ijms24097728"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1002\/chem.200400835","article-title":"3-Fluoropiperidines and N-Methyl-3-fluoropiperidinium Salts: The Persistence of Axial Fluorine","volume":"11","author":"Aiming","year":"2005","journal-title":"Chem. Eur. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2261","DOI":"10.5958\/0974-360X.2020.00407.2","article-title":"Biological active fluorobenzoates of piperidine range","volume":"13","author":"Maksatova","year":"2020","journal-title":"Res. J. Pharm. Technol."},{"key":"ref_31","first-page":"5143","article-title":"An approach of quantum chemical methods for the development and substantiation of the structure of new piperidine compounds","volume":"64","author":"Boshkayeva","year":"2021","journal-title":"Egypt. J. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"125","DOI":"10.18321\/ectj822","article-title":"The search for biologically active compounds in the series of N-ethoxyethylpiperidine derivatives","volume":"21","author":"Issayeva","year":"2019","journal-title":"Eurasian Chem.-Technol. J."},{"key":"ref_33","first-page":"493","article-title":"A simple method of estimating fifty percent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am. J. Hyg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"542","DOI":"10.2307\/1588616","article-title":"The haemagglutination-elution pattern as a marker in characterizing Newcastle disease virus","volume":"14","author":"Spalatin","year":"1970","journal-title":"Avian Dis."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2540\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:49:34Z","timestamp":1760032174000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2540"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,10]]},"references-count":35,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["molecules30122540"],"URL":"https:\/\/doi.org\/10.3390\/molecules30122540","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,10]]}}}