913335-87-2Relevant academic research and scientific papers
Synthesis, conformational characteristics and anti-influenza virus A activity of some 2-adamantylsubstituted azacycles
Setaki, Despina,Tataridis, Dimitris,Stamatiou, George,Kolocouris, Antonios,Foscolos, George B.,Fytas, George,Kolocouris, Nicolas,Padalko, Elizaveta,Neyts, Johan,Clercq, Erik De
, p. 248 - 273 (2008/02/07)
The broad-spectrum antiviral activity of 2-(2-adamantyl)piperidines 11, 13a,b, and 15, 3-(2-adamantyl)pyrrolidines 27, 21a-g and 2-(2-adamantylmethyl)piperidines 30, 32a-c, and 35a-d was examined. Several compounds in the new series were potent against influenza A H3N2 virus. When 1-aminoethyl pharmacophore group of 2-rimantadine 4 (2-isomer of rimantadine) is included into a saturated nitrogen heterocycle, see compound 11, potency was retained. The diamine derivatives 21e-g and particularly 35a-c possessing three pharmocophoric groups, that is, the adamantyl and the two amine groups, exhibited high potency. The new compounds did not afford specific activity at non-toxic concentrations against any of the other viruses tested. According to NMR spectroscopy and molecular mechanics calculations it is striking that the parent structures 11 and 27 adopt a fixed trans conformation around C2{single bond}C2′ bond. In the parent amines, which proved to be active compounds, the distance between nitrogen and adamantyl pharmacophoric groups was different; N{single bond}C2′ distance is 3.7, 3.8 A for 27, 30 and 2.5 A for 11 suggesting that M2 receptor site can accommodate different in size and orientation lipophilic cages.
Novel 3-(2-adamantyl)pyrrolidines with potent activity against influenza A virus - Identification of aminoadamantane derivatives bearing two pharmacophoric amine groups
Stamatiou, George,Kolocouris, Antonios,Kolocouris, Nicolas,Fytas, George,Foscolos, George B,Neyts, Johan,De Clercq, Erik
, p. 2137 - 2142 (2007/10/03)
The 3-(2-adamantyl)pyrrolidines 8a-g, 14 were synthesized and evaluated for activity against influenza A virus. The parent N-H compound 14 was several times more active than amantadine against H2N2 and H3N2 influenza A virus. The combined use of NMR spectroscopy and computational chemistry showed that the conformation around the pyrrolidine-adamantyl carbon-carbon bond is trans and the pyrrolidine heterocycle has an envelope conformation with C-2 out of the plane of the other ring atoms. N-Dialkylaminoethyl substitution of compound 14 resulted in the potent diamine analogues 8e,f,g. Interestingly, their lactam amine precursors were also active. Compounds 8e,f,g are the first adamantane derivatives, bearing two amine groups, reported to be active against influenza A virus.
