Physicochemical prediction of a brain–blood distribution profile in polycyclic amines

Medicinal chemistry of polycyclic cage compounds in drug discovery research

“…Foremost amongst these was the evaluation of the N-substituted 8,11-oxapentacylco undecanes 14 for ion channel activity where potential-dependent blocking of L-type Ca 2+ channels was observed (Malan et al, 1996;Malan et al, 2000). The pentacycloundecane derivatives of 14 have also been shown to effectively cross the blood-brain barrier (Zah et al, 2003) and show potential as carriers for the delivery of drugs with low blood-brain barrier permeability. Modulation of the sodium and delayed rectifier potassium currents has also been described for the ring-enlarged derivative, 6-benzylamino-3-hydroxyhexacyclo[6.5.0.0.…”

Pentacycloundecylamines and conjugates thereof as chemosensitizers and reversed chloroquine agents

“…PCU scaffolds also have the potential to increase the permeation of privileged molecules over biological membranes and possibly into the parasite vacuole when covalently bound. Studies by Zah et al, 2003 andPrins et al, 2009 illustrated the ability of PCU scaffolds to significantly improve the permeability of privileged molecules. 24,25 It is also suggested that the bulky aza-PCU scaffold will protect the terminal tertiary amino group from metabolism via N-dialkylation.…”

“…Studies by Zah et al, 2003 andPrins et al, 2009 illustrated the ability of PCU scaffolds to significantly improve the permeability of privileged molecules. 24,25 It is also suggested that the bulky aza-PCU scaffold will protect the terminal tertiary amino group from metabolism via N-dialkylation. N-dialkylation of CQ reduces its lipid solubility and may lead to an increase in the potential for cross-resistance with CQ.…”

NMR elucidation of novel SQ109 derivatives

“…Adamantane is the most studied which has led to the discovery of numerous pharmaceutical candidates [1][2][3][4][5][6]. The polycyclic 'cage' has been reported to improve the pharmacokinetic and pharmacological properties of known drug candidates [6][7][8][9][10]. However, its pharmaceutical importance only drew increased attention after the discovery of 1-amino-adamantane or amantadine.…”