{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T14:07:22Z","timestamp":1761919642261},"reference-count":58,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2013,6,1]],"date-time":"2013-06-01T00:00:00Z","timestamp":1370044800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antivir Chem Chemother"],"published-print":{"date-parts":[[2013,6]]},"abstract":"<jats:sec><jats:title>Background:<\/jats:title><jats:p> Amantadine constitutes an interesting, diamond crystal lattice-shaped, antivirally active amine with an inhibitory effect on influenza A viruses causing common \u2018flu\u2019 in humans. Unfortunately, amantadine forfeited most of its therapeutic potential because of resistance development in recent influenza A virus isolates. The antiviral efficacy of amantadine congeners can be chemically modified, resulting in re-constitution, improvement and\/or extension of antiviral activities mediated by amino-adamantyls. <\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p> Newly synthesized compounds were evaluated towards HIV type-1 (HIV-1) replication in primary human lymphocytes. One N-phenacyl amantadine derivative was investigated for inhibiting the in vitro replication of respiratory viruses (influenza A viruses, influenza B virus, human parainfluenza virus type 3 and severe acute respiratory syndrome coronavirus). <\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p> Two ketone-stabilized 1-adamantyl singlet nitrenes were discovered serendipitously. To our best knowledge these are the first persistently stable nitrenes to be reported. Their structure was proved by determining the X-ray single crystal structure of one hydrolytic elaboration product. This salt adduct revealed an incommensurately modulated crystal structure, which was solved by extensive computational refinement. We could show that ketone-stabilized 1-adamantyl singlet nitrenes are versatile synthons for the synthesis of antiviral drug candidates. An amantadine\u2013folate conjugate was inhibitory on HIV-1 replication in primary human lymphocytes, and one N-phenacyl amantadine derivative was inhibitory towards low pathogenic avian influenza A virus (H5N1) replication in vitro. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p> These results indicate that the aromatic-aliphatic ketone-stabilized 1-adamantyl singlet nitrenes, beyond being of fundamental interest in organic chemistry, represent versatile synthons for the synthesis of new amantadine-related potentially antiviral drugs. <\/jats:p><\/jats:sec>","DOI":"10.3851\/imp2485","type":"journal-article","created":{"date-parts":[[2012,12,12]],"date-time":"2012-12-12T15:34:04Z","timestamp":1355326444000},"page":"113-128","update-policy":"http:\/\/dx.doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Antiviral Agents Derived from Novel 1-adamantyl Singlet Nitrenes"],"prefix":"10.1177","volume":"23","author":[{"given":"Andreas J","family":"Kesel","sequence":"first","affiliation":[{"name":"Chamm\u00fcnsterstr 47, Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans-Christoph","family":"Weiss","sequence":"additional","affiliation":[{"name":"Currenta GmbH & Co. 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