Synthesis and pharmacological evaluation of several ring-contracted amantadine analogs

Abstract

The synthesis of several (3-noradamantyl)amines, [(3-noradamantyl)methyl]amines, (3,7-dimethyl-1-bisnoradamantyl)amines, and [(3,7-dimethyl-1-bisnoradamantyl)methyl]amines is reported. They were evaluated against a wide range of viruses and one of them inhibited the cytopathicity of influenza A virus at a concentration similar to that of amantadine. Several of the new polycyclic amines show an interesting activity as NMDA receptor antagonists. A rimantadine analogue displayed significant trypanocidal activity. Moreover, to further characterize the pharmacology of these compounds, their effects on dopamine uptake were also assessed.

New oxapolycyclic cage amines with NMDA receptor antagonist and trypanocidal activities

“…22 To evaluate if the synthesized compounds were able to antagonize NMDA receptors, we have measured their effect on the increase in intracellular calcium evoked by glutamate or NMDA (both 100 lM, in the presence of 10 lM of glycine) on rat cultured cerebellar granule neurons. 23 Compounds 14, 17a, 29a and 29b had IC 50 values (NMDA) that were in the micromolar order, similar to memantine (Table 1).…”

“…23 Cells were grown on 10 mm poly-L-lysine coated glass cover slips, and used for the experiments after 7-14 days in vitro. Cells were loaded with 6 lM Fura-2 AM (invitrogen-molecular probes) for 45 min.…”

The many faces of the adamantyl group in drug design

“…In Parkinson's disease, 1 acts directly on the D2 dopamine receptor, resulting in enhanced dopamine release, while inhibiting post-synaptic reuptake. Compound 1 has antimuscarinic and antiglutamatergic properties via the non- [10]. Memantine (2) is a noncompetitive, moderate affinity NMDA receptor antagonist used to treat moderate to severe Alzheimer's disease.…”

Double Methylenecyclopentane Annulation of Succinimides: Easy Access to 3,7‐Dioxobicyclo[3.3.0]octane‐1,5‐dicarboximides

“…[23,24] We are currently pursuing the application of ketones 3 and 10 or diene 7 for the preparation of new functionalized cage compounds related to those previously prepared by the group, [8] as scaffolds for potentially active compounds. [25,26] …”