Fr Francium

Polycyclic cage scaffolds have been successfully used in the development of numerous lead compounds demonstrating activity in the central nervous system (CNS). Several neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, schizophrenia, and stroke, as well as drug abuse, can be modulated with polycyclic cage derivatives. These cage moieties, including adamantane and pentacycloundecane derivatives, improve the pharmacokinetic and pharmacodynamic properties of conjugated parent drugs and serve as an important scaffold in the design of therapeutically active agents for the treatment of neurological disorders. In this Minireview, we focus on the recent developments in the field of polycyclic cage compounds, as well as the relationship between the lipophilic character of these cage-derived drugs and the ability of such compounds to target and reach the CNS and improve the pharmacodynamic properties of compounds conjugated to it.

Scaffolds for neuroprotection: Less than five per cent of small-molecule drugs are able to cross the blood–brain barrier (BBB). Developments in the design of compounds incorporating lipophilic, polycyclic structures have been under intense investigation in recent years. Conjugation of privileged moieties and known drug structures to these polycyclic structures has enhanced the delivery of neuroactive drugs across the BBB with subsequent neuroprotective and/or neurorestorative activity.