The lipophilic bullet hits the targets: Medicinal chemistry of adamantane derivatives

摘要

The article reviews concentrates on the numerous applications in medicinal chemistry and drug development of adamantane derivatives. The aminoadamantanes are synthetic drugs that have not been inspired by natural products like numerous other drugs. There are, however, also isolates from Nature incorporating an adamantane motif, like 'nature's marvel,' tetrodotoxin. Like amantadine, it also blocks an ion channel, the sodium channel. This potent pharmaceutical activity may be, at least in part, attributed to its rigid dioxaadamantane core. The mutations, in turn, destabilize the closed channel, making it easier to open, which counters the effect of the aminoadamantanes. This model could be advantageous for drug design, because drugs that are larger than hydrated ions do have to overcome a higher energetic barrier to find a binding site inside a pore than to bind to the channel complex from the membrane-facing outside.