Aminoadamantane derivatives

Amidines and guanidines, 30 (1993) 206 Aminoadamantane derivatives, 18 (1981) 1 Aminopterins as antitumour agents, 25... 

Extensive investigations have been performed related to the synthesis of new adamantane derivatives with better therapeutic actions and less adverse effects. For example, it has been proved that adamantylamino-pyrimidines and -pyridines are strong stimulants of mmor necrosis factor-a (TNF-a) [132]. TNF is a substance that can improve the body s namral response to cancer by killing cancer cells. Another example is 1,6-diaminodiamantane [87], which possesses an antitumor and antibacterial activity. Also, many derivatives of aminoadamantanes have antiviral activity like 3-(2-adamantyl) pyrolidines with two pharmacophoric amine groups, which have antiviral activity against influenza-A virus [133]. 

Removal of FMOC-OH can be achieved by liquid-liquid extraction (normally into pentane).A more elegant method of preventing interference of FMOC-OH is to react excess FMOC with a very hydrophobic amine (e.g. I -aminoadamantane) to form a derivative which elutes after the peaks of interest. 

Amanatdine and Rimantadine are the 1-aminoadamantane hydrochloride and its a-methyl derivative. Both compounds are cyclic amines that inhibit the uncoating of the influenza A viral RNA within the infected host cell and hence prevent its replication. They are effective in prevention and treatment of influenza A infection in high risk individuals [13]. 

Fig. 9.8 Chemical structures of memantine and its derivatives. Amantadine (1-aminoadamantane) (a) memantine (l-amino-3,5-dimethyladamantane) (b) NitroMemantine (c) and 1-amino-3,...

As an example of the influence of basicity and amphiphily of SDAs, the isosteric series of four adamantane derivatives has been investigated (Fig. 4). Whereas the most basic 1-aminoadamantane is one of the most active and versatile structure-directing template molecules, the apolar 1-methyl-adamantane has not been a successful SDA. 1-Hydroxyadamantane is a poor SDA and 1-bromo-adamantane is even less active. 

The pK values of acids (59)—(62) have been measured and used to show the inadequacy of a a-inductive model. A field model qualitatively predicts the observed order of acidities. The role of through-bond effects with a stereochemical requirement in these results is not clear. The dissociation constant of the cation derived from 1-aminoadamantane has been recorded. ... 

Chapter 10 - 2-(l-adamantyl)indole, synthesized by Fischer reaction, was transformed into 3-dimethylaminomethyl derivative according Mannich reaction. It was obtained corresponding quaternary salts soluble in water. 2-adamantylaminocarbonylindole and 2,9-di(adamantylaminocarbonyl)-lH,10H-benzo[e]pyrrolo[3,2-g]indole were obtained by interaction between 1-aminoadamantane and 2-indolylcarbonic acid. The synthesized compounds revealed biological activity. 

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