Influence of an additional 2-amino substituent of the 1-aminoethyl pharmacophore group on the potency of rimantadine against influenza virus A.
Tataridis D, Fytas G, Kolocouris A, Fytas C, Kolocouris N, Foscolos GB, Padalko E, Neyts J, De Clercq E.
We examined whether the incorporation of a second amino group into the 1-aminoethyl pharmacophore of rimantadine 2 and into the piperidine pharmacophore of the heterocyclic rimantadine 4 was compatible with anti-influenza virus A activity. The new synthetic molecules are capable of forming two hydrogen bonds within the receptor. We identified molecules 8 and 16, bearing the adamantyl and 1,2-diaminoethyl groups, which are equipotent to rimantadine 2 bearing the adamantyl and 1-aminoethyl pharmacophore groups. Interestingly, diamino compound 16 is a 4-fold more potent inhibitor than its parent monoamino heterocyclic rimantadine 4 propably because of additional hydrogen bonding interactions with the M2 protein receptor.