Synthesis and pharmacological evaluation of (2-oxaadamant-1-yl)amines

Abstract

The synthesis of several (2-oxaadamant-1-yl)amines is reported. They were evaluated as NMDA receptor antagonists and several of them were more active than amantadine, but none was more potent than memantine. None of the tested compounds displayed antiviral activity. Two of the derivatives showed a significant level of trypanocidal activity.

New oxapolycyclic cage amines with NMDA receptor antagonist and trypanocidal activities

“…The positive effect of having methyl groups directly attached to the polycyclic structure was also noticed in our previous work with (2-oxaadamant-1-yl)amines, 15 with the 3-methyl and 3-ethyl derivatives being much more active than the unsubstituted compounds. However, among the products reported here, the introduction of a 5-methyl or a 5-ethyl group did not increase the activity (e.g., series 7/28a/ 28b or 17a/29a or 15/31a).…”

“…8 Moreover, very recently, we found that several (3-alkyl-2-oxadamant-1-yl)amines showed significant activity against bloodstream form T. brucei. 15 We therefore investigated if the newly synthesized oxapolycyclic cage amines reported here also displayed significant activity against this parasite.…”

“…Taking into account that in our previous work with 2-oxaadamant-1-ylamines we found that 3-alkyl derivatives were more potent than the corresponding 3-unsubstituted derivatives, 15 we also planned to carry out the synthesis and evaluation of 5-alkyl derivatives of amine 7.…”

“…2). 15 Following our work on the synthesis of oxapolycyclic compounds as analogs of amantadine and memantine, we now describe the synthesis and biological evaluation of a series of (1,2,3,5, 6,7-hexahydro-1,5:3,7-dimethano-4-benzoxonin-3-yl)amines, and show that they contain structural features necessary for NMDA receptor antagonist activity and trypanocidal activity.…”

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] …”