Are the 2-Isomers of the Drug Rimantadine Active Anti-Influenza a Agents?

Abstract

There is a lack of information in the medical chemistry literature concerning the anti-influenza A activity of the drug rimantadine's 2-isomer (2-rimantadine). We now present results showing that, although 2-adamantanamine (2-amantadine) 3 is only moderately active, some 2-rimantadine analogues are effective anti-influenza A virus agents in vitro. The 2-rimantadine analogues and their spirocyclobutane and spirocyclopentane congeners were synthesized through interesting routes. The 2-rimantadine analogues were 2-4 times more potent than rimantadine 2 against influenza virus A H2N2 strain; their spirocyclobutane congeners proved equally active to rimantadine 2. Two compounds exhibited a similar activity and one of the compounds was was fourfold more potent than rimantadine 2 against H3N2 strain.

The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

“…93 was 7.9 times more potent than amantadine and 3.7 times more potent than rimantadine, but 94 was significantly less potent than amantadine. 155 …”

Antiviral agents active against influenza A viruses

“…In addition to amantadine and rimantadine, various new adamantan(amin)e derivatives have shown marked activity against influenza A (H2N2 and/or H3N2) [16][17][18][19][20][21][22] (FIG. 3b).…”

Another ten stories in antiviral drug discovery (part C): “Old” and “new” antivirals, strategies, and perspectives

“…piperidine, 2-(1-adamantyl-2-methyl)pyrrolidine, and many others [77][78][79][80][81][82][83][84][85] (as reviewed by Lagoja and De Clercq 86 ). 87 In all cases, the anti-influenza A virus activity noted for these compounds compared favorably to that of amantadine when evaluated under the same experimental conditions.…”