Novel 3-(2-Adamantyl)pyrrolidines with potent activity against influenza A virus—identification of aminoadamantane derivatives bearing two pharmacophoric amine groups
Identifieur interne : 001822 ( Main/Exploration ); précédent : 001821; suivant : 001823Novel 3-(2-Adamantyl)pyrrolidines with potent activity against influenza A virus—identification of aminoadamantane derivatives bearing two pharmacophoric amine groups
Auteurs : George Stamatiou [Grèce] ; Antonios Kolocouris [Grèce] ; Nicolas Kolocouris [Grèce] ; George Fytas [Grèce] ; George B. Foscolos [Grèce] ; Johan Neyts [Belgique] ; Erik De Clercq [Belgique]Source :
- Bioorganic & Medicinal Chemistry Letters [ 0960-894X ] ; 2001.
Descripteurs français
- Pascal (Inist)
- Adamamtane dérivé, Amine tertiaire, Analyse conformationnelle, Antiviral, Composé saturé, Composé tricyclique, Diamine, Hétérocycle azote, In vitro, Modèle moléculaire, Modélisation, Méthode dynamique moléculaire, Pyrrolidine(3-[2-adamantyl]-1-[2-(dialkylamino)éthyl]), Relation structure activité, Synthèse chimique, Virus grippal A.
English descriptors
- KwdEn :
- Teeft :
- Amine, Amine groups, Aminoadamantane derivatives, Aminoadamantanes, Catalytic hydrogenation, Chem, Computational chemistry, Conformation, Conformers, Derivative, Elsevier science, Energy conformations, Energy conformers, Envelope conformation, Gauche, Gauche interactions, Grid scan search analysis, Hong kong, Kolocouris, Lactam amine precursors, Lett, Molecular mechanics calculations, Other atoms, Parent amine, Parent pyrrolidine, Potent aminoadamantanes, Protonated form, Pyrrolidine, Pyrrolidine heterocycle, Trans, Virus activity.
Abstract
Abstract: 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.
Pyrrolidines 14, 8a,e,g were synthesized and found active against H2N2 and H3N2 influenza A virus. Through a combination of NMR spectroscopy and molecular mechanics calculations it was shown that the parent 3-(2-adamantyl)pyrrolidine 14 adopts a trans conformation around C3–C2′ bond and an E(2) pyrrolidine conformation. Compounds 8e,g are the first adamantane derivatives, bearing two amine groups, reported to be active against influenza A virus.fx5187
Url:
DOI: 10.1016/S0960-894X(01)00388-2
Affiliations:
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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.</div><div type="abstract">Pyrrolidines 14, 8a,e,g were synthesized and found active against H2N2 and H3N2 influenza A virus. Through a combination of NMR spectroscopy and molecular mechanics calculations it was shown that the parent 3-(2-adamantyl)pyrrolidine 14 adopts a trans conformation around C3–C2′ bond and an E(2) pyrrolidine conformation. Compounds 8e,g are the first adamantane derivatives, bearing two amine groups, reported to be active against influenza A virus.fx5187 </div></front></TEI><affiliations><list><country><li>Belgique</li><li>Grèce</li></country><region><li>Province du Brabant flamand</li><li>Région flamande</li></region><settlement><li>Louvain</li></settlement><orgName><li>Katholieke Universiteit Leuven</li></orgName></list><tree><country name="Grèce"><noRegion><name sortKey="Stamatiou, George" sort="Stamatiou, George" uniqKey="Stamatiou G" first="George" last="Stamatiou">George Stamatiou</name></noRegion><name sortKey="Foscolos, George B" sort="Foscolos, George B" uniqKey="Foscolos G" first="George B" last="Foscolos">George B. Foscolos</name><name sortKey="Foscolos, George B" sort="Foscolos, George B" uniqKey="Foscolos G" first="George B" last="Foscolos">George B. Foscolos</name><name sortKey="Fytas, George" sort="Fytas, George" uniqKey="Fytas G" first="George" last="Fytas">George Fytas</name><name sortKey="Kolocouris, Antonios" sort="Kolocouris, Antonios" uniqKey="Kolocouris A" first="Antonios" last="Kolocouris">Antonios Kolocouris</name><name sortKey="Kolocouris, Nicolas" sort="Kolocouris, Nicolas" uniqKey="Kolocouris N" first="Nicolas" last="Kolocouris">Nicolas Kolocouris</name></country><country name="Belgique"><region name="Région flamande"><name sortKey="Neyts, Johan" sort="Neyts, Johan" uniqKey="Neyts J" first="Johan" last="Neyts">Johan Neyts</name></region><name sortKey="De Clercq, Erik" sort="De Clercq, Erik" uniqKey="De Clercq E" first="Erik" last="De Clercq">Erik De Clercq</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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