{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T19:43:20Z","timestamp":1769024600689,"version":"3.49.0"},"reference-count":32,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T00:00:00Z","timestamp":1653955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2020-803"],"award-info":[{"award-number":["075-15-2020-803"]}]},{"name":"MSU Development Program","award":["075-15-2020-803"],"award-info":[{"award-number":["075-15-2020-803"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The application of non-planar scaffolds in drug design allows for the enlargement of the chemical space, and for the construction of molecules that have more effective target\u2013ligand interactions or are less prone to the development of resistance. Among the works of the last decade, a literature search revealed spirothiazamenthane, which has served as a lead in the development of derivatives active against resistant viral strains. In this work, we studied the novel molecular scaffold, which resembles spirothiazamenthane, but combines isoxazoline as a heterocycle and cyclooctane ring as a hydrophobic part of the structure. The synthesis of new 3-nitro- and 3-aminoisoxazolines containing spiro-fused or 1,2-annelated cyclooctane fragments was achieved by employing 1,3-dipolar cycloaddition of 3-nitro-4,5-dihydroisoxazol-4-ol 2-oxide or tetranitromethane-derived alkyl nitronates with non-activated alkenes. A series of spiro-sulfonamides was obtained by the reaction of 3-aminoisoxazoline containing a spiro-fused cyclooctane residue with sulfonyl chlorides. Preliminary screening of the compounds for antiviral, antibacterial, antifungal and antiproliferative properties in vitro revealed 1-oxa-2-azaspiro[4.7]dodec-2-en-3-amine and 3a,4,5,6,7,8,9,9a-octahydrocycloocta[d]isoxazol-3-amine with activity against the influenza A\/Puerto Rico\/8\/34 (H1N1) virus in the submicromolar range, and high values of selectivity index. Further study of the mechanism of the antiviral action of these compounds, and the synthesis of their analogues, is likely to identify new agents against resistant viral strains.<\/jats:p>","DOI":"10.3390\/molecules27113546","type":"journal-article","created":{"date-parts":[[2022,5,31]],"date-time":"2022-05-31T09:24:29Z","timestamp":1653989069000},"page":"3546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Bicyclic Isoxazoline Derivatives: Synthesis and Evaluation of Biological Activity"],"prefix":"10.3390","volume":"27","author":[{"given":"Kseniya N.","family":"Sedenkova","sequence":"first","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristian S.","family":"Andriasov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina G.","family":"Eremenko","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuri K.","family":"Grishin","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-5890","authenticated-orcid":false,"given":"Vera A.","family":"Alferova","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia"},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna A.","family":"Baranova","sequence":"additional","affiliation":[{"name":"Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021 Moscow, Russia"},{"name":"Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya 16\/10, 117997 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikolay A.","family":"Zefirov","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olga N.","family":"Zefirova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5224-3771","authenticated-orcid":false,"given":"Vladimir V.","family":"Zarubaev","sequence":"additional","affiliation":[{"name":"Saint Petersburg Pasteur Research Institute of Epidemiology and Microbiology, 14 Mira St., 197101 Saint Petersburg, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulia A.","family":"Gracheva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena R.","family":"Milaeva","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena B.","family":"Averina","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3, 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.drudis.2013.07.011","article-title":"Fragment-based hit identification: Thinking in 3D","volume":"18","author":"Morley","year":"2013","journal-title":"Drug Discov. 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