General Applications of Diamondoids

Each successively higher diamondoid family shows increasing structural complexity and varieties of molecular geometries. Sui generis properties of diamondoids have provoked an extensive range of inquiries in different fields of science and technology. For example, they have been used as templates for crystallization of zeolite catalysts [25], the synthesis of high-temperature polymers [26], and in pharmacology.

In pharmacology, two adamantane derivatives, Amantadine (1-adaman-taneamine hydrochloride) and Rimantadine (a-methyl-1-adamantane methylamine hydrochloride) have been well known because of their antiviral activity (Figure 3.5). The main indication of these drugs is prophylaxis and treatment of influenza A viral infections. They are also used in the treatment of Parkinsonism and inhibition of hepatitis C virus (HCV) [27]. Memantine (1-amino-3,5-dimethyladamantane) has been reported effective in slowing the progression of Alzheimer's disease [27].

Extensive investigations have been performed related to synthesis of new adamantane derivatives with better therapeutic actions and less adverse effects. For example, it has been proved that adamantylaminopyrimidines and -pyridines are strong stimulants of tumor necrosis factor-a (TNF-a) [28], and 1,6-diaminodiamantane possesses an antitumor and antibacterial activity [29]. Many derivatives of aminoadamantanes have antiviral activity and 3-(2-adamantyl) py-rolidines with two pharmacophoric amine groups have antiviral activity against influenza A virus [30].

Figure 3.5. (a) Amantadine. (b) Rimantadine. (c) Memantine.

Figure 3.5. (a) Amantadine. (b) Rimantadine. (c) Memantine.

Some derivatives of adamantane with antagonist or agonist effects have also been synthesized. For instance, monocationic and dicationic adamantane derivatives block the a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors [31-33] and also 5-hydroxytryptamine (5-HT3) receptors [34]. The monocationic and dicationic adamantane derivatives have been employed to investigate the topography of the channel binding sites of AMPA and NMDA receptors [32]. A dicationic adamantane derivative has been exploited as a selective and specific marker of the native AMPA receptor assembly to determine the distribution of AMPA receptors subtypes among populations of rat brain cells [31,33]. Other instances include antagonism of 5-HT3 and agonism of 5-HT4 receptors by aza(nor)adamantanes [35], P2X7 receptor antagonism by adamantane amides [36], antagonism of voltage-gated calcium channels and probably activation of y-aminobutyric acid (GABA) receptors by an adamantane amine derivative that results in its anti-convulsive and antinociceptive actions [37], and inhibition of glucosylcerami-dase enzyme and glycolipid biosynthesis by a deoxynojirimycin-bearing adaman-tane derivative leading to strong anti-inflammatory and immunosuppressive activities [38].

Attaching some short peptidic sequences to adamantane makes it possible to design novel antagonists. The bradykinin antagonist is an example [39]. The adamantane-based peptidic bradykinin analogue was utilized in the structure-activity relationship (SAR) studies on the bradykinin receptors and showed apotent activity in inhibition of bradykinin-induced cytokine release and stimulation of histamine release [39]. In an attempt to design the (3 -turn peptide mimics, the aspartic acid and lysine were attached to each amine group of 1,3-diaminoadamantane in the form of an amide bond [40]. The said compound displayed some degrees of fibrinogen-GPIIB/IIIA antagonism [40].

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