Polycyclic cage structures as lipophilic scaffolds for neuroactive drugs.
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.
School of Pharmacy, University of the Western Cape, Private Bag X17, Bellville 7535, South Africa.
Jacques
J
Joubert
Werner J
WJ
Geldenhuys
Cornelis J
CJ
Van der Schyf
Douglas W
DW
Oliver
Hendrik Gert
HG
Kruger
Thavendran
T
Govender
Sarel F
SF
Malan
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D003516:Cycloparaffins / Q000138:chemical synthesis / Q000627:therapeutic use; D004298:Dopamine / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D051379:Mice; D008995:Monoamine Oxidase / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis / Q000627:therapeutic use*; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018696:Neuroprotective Agents / Q000138:chemical synthesis / Q000627:therapeutic use*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D017480:Receptors, sigma / Q000037:antagonists & inhibitors / Q000378:metabolism
D020746:Calcium Channels, L-Type; D003516:Cycloparaffins; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D017480:Receptors, sigma; D019001:Nitric Oxide Synthase; D008995:Monoamine Oxidase; D004298:Dopamine