Synthesis of 2-(2-adamantyl)piperidines and structure anti-influenza virus A activity relationship study using a combination of NMR spectroscopy and molecular modeling

Journal URL: http://www.sciencedirect.com/science/journal/0960894

Are the 2-isomers of the drug rimantadine active anti-influenza A agents?

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

Influence of an additional 2-amino substituent of the 1-aminoethyl pharmacophore group on the potency of rimantadine against influenza virus A

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. © 2006 Elsevier Ltd. All rights reserved

Synthesis and Antiviral Activity Evaluation of Some Aminoadamantane Derivatives

The synthesis of some spiro[cyclopropane-1,2′-adamantan]-2-amines and methanamines and some spiro[pyrrolidine-2,2′-adamantanes] is described. The title compounds were evaluated against a wide range of viruses (influenza A, influenza B, parainfluenza 3, RSV, HSV-1,TK-HSV-1, HSV-2, vaccinia, vesicular stomatitis, polio 1, coxsackie B4, sindbis, semliki forest, Reo 1, HIV-1, and HIV-2), and some of them (compounds 6b, 6c, 9a, 16a, 16b, and 17) inhibited the cytopathicity of influenza A virus at a concentration significantly lower than that of amantadine and also significantly lower than the concentrations at which they proved cytotoxic to the host cells. None of the new aminoadamantane derivatives was active against influenza B virus or any of the other viruses tested, which points to their specificity as anti-influenza A virus agents. © 1994, American Chemical Society. All rights reserved

Synthesis and anti-HIV activity of some new aminoadamantane heterocycles

A new class of aminoadamantane heterocycles has been synthesized and examined for anti-HIV activity. Three compounds proved to be active against the replication of HIV-1 in MT-4 cells with an EC50 ranging from 3.6 to 75.2 μM. No activity was noted with any of the compounds against HIV-2

Synthesis and antiviral activity evaluation of some new aminoadamantane derivatives. 2

The synthesis of some new aminoadamantane derivatives is described. The new compounds were evaluated against a wide range of viruses [influenza A H1N1, influenza A H2N2, influenza A H3N2, influenza B, parainfluenza 3, herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), thymidine kinase- deficient (TK-) HSV-1, vaccinia, vesicular stomatitis, polio 1, Coxsackie B4, Sindbis, Semliki forest, Reo 1, varicella-zoster virus (VZV), TK- VZV, human cytomegalovirus (HCMV), and human immunodeficiency virus type 1 (HIV- 1) and type 2 (HIV-2)]. Some of them proved markedly active against the influenza A H2N2 (compounds 4a,b, 5a, 6a, and 7a), H3N2 (compounds 5a, 6a, and 7a), and H1N1 (compounds 4b,c and 6d). Since compounds 5a, 6a, and 7a, amantadine, and rimantadine showed the same comparative pattern of potency against influenza strains H2N2, H3N2, and B, it may postulated that they act according to a similar mechanism, with regard to their 'amine' effect, on the M2 ion channel of influenza A (H1N1, H2N2, or H3N2). In general, no significant activity was noted with any of the new compounds against any of the other viruses tested, making their activity against influenza virus more specific and striking. Borderline activity was noted with some of the compounds (4b,c, 5a-c, and 8a) against HIV-1