%0 Journal Article
%T 1,2-¦¡nnulated Adamantane Heterocyclic Derivatives as Anti-Influenza ¦¡ Virus Agents
%A Giannakopoulou
%A Erofili
%A Kolocouris
%A Antonios
%A Konstantinidi
%A Athina
%A Pardali
%A Vasiliki
%A Zoidis
%A Grigoris
%J -
%D 2019
%R 10.5562/cca3540
%X Sa£¿etak 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. This work is licensed under a Creative Commons Attribution 4.0 International License
%K 1
%K 2-Annulated adamantane derivatives
%K Anti-influenza A virus agents
%K H3N2
%K H1N1
%K Rimantadine
%K Amantadine
%K SAR
%K M2 protein
%K POPC hydrated bilayers
%U https://hrcak.srce.hr/index.php?show=clanak&id_clanak_jezik=330672