@article{3026011,
    title = "1,2-αnnulated adamantane heterocyclic derivatives as anti-influenza α virus agents",
    author = "Pardali, V. and Giannakopoulou, E. and Konstantinidi, A. and Kolocouris, A. and Zoidis, G.",
    journal = "Croatica Chemica Acta",
    year = "2019",
    volume = "92",
    number = "2",
    pages = "211-228",
    publisher = "Croatian Chemical Society (Hrvatsko kemijsko drustvo)",
    issn = "0011-1643",
    doi = "10.5562/cca3540",
    abstract = "In this report we review our results on the development of 1,2-annulated adamantane heterocyclic derivatives and we discuss the structure-activity relationships obtained from their biological evaluation against influenza A virus. We have designed and synthesized numerous potent 1,2-annulated adamantane analogues of amantadine and rimantadine against influenza A targeting M2 protein the last 20 years. For their synthesis we utilized the key intermediates 2-(2-oxoadamantan-1-yl)acetic acid and 3-(2-oxoadamantan-1-yl)propanoic acid, which were obtained by a simple, fast and efficient synthetic protocol. The latter involved the treatment of protoadamantanone with different electrophiles and a carbon-skeleton rearrangement. These ketoesters offered a new pathway to the synthesis of 1,2-disubstituted adamantanes, which constitute starting materials for many molecules with pharmacological potential, such as the 1,2-annulated adamantane heterocyclic derivatives. To obtain additional insight for their binding to M2 protein three structurally similar 1,2-annulated adamantane piperidines, differing in nitrogen position, were studied using molecular dynamics (MD) simulations in palmitoyl-oleoyl-phosphatidyl-choline (POPC) hydrated bilayers. © 2019 Croatian Chemical Society. All rights reserved."
}