New oxapolycyclic cage amines with NMDA receptor antagonist and trypanocidal activities

The Lipophilic Bullet Hits the Targets: Medicinal Chemistry of Adamantane Derivatives

“…360 For this class of trypanocides, a decane- (or “oxadecane” substitution, for that matter) substituent at C1 was shown to be ideal in terms of in vitro trypanocidal potency. Lastly, oxaheterocyclic amines like oxaadamantane 198 361 and the secondary amine 201 362 have also been shown to display anti- T. brucei activity in vitro ; furthermore, the latter oxapolycyclic amine is devoid of any NMDA-receptor antagonism, which could be useful to avoid CNS-related side effects when using these compounds to combat T. brucei and other trypanosomes clinically. Recent additions to the library of adamantane-derived trypanocidal compounds are amino alcohols such as protoadamantane 202 and 2-hydroxyderivative 203 363 as well as spiro carboxyclic adamantylidene diketopiperazines.…”

Memantine, an Antagonist of the NMDA Glutamate Receptor, Affects Cell Proliferation, Differentiation and the Intracellular Cycle and Induces Apoptosis in Trypanosoma cruzi

“…Moreover, our group characterized a glutamate transporter [12] which is able to bind NMDA, behaving as a glutamate receptor (unpublished data). In addition, analogs of amantadine and Memantine (1,2,3,5,6,7-hexahydro-1,5:3,7-dimethano-4-benzoxonin-3-yl)amines with NMDA receptor antagonist activity were also demonstrated to have significant trypanocidal activity against Trypanosoma brucei [13]. These data led us to hypothesize that trypanocidal activities are present in compounds directed against mammalian glutamate receptors.…”

Antibacterial activity of novel benzopolycyclic amines

“…8 4.1.4. 2-Chloro-N-(9-chloro-5,6,8,9,10,11-hexahydro-7H-5,9:7,11-dimethanobenzo [9]annulen-7-yl)acetamide, 6 A solution of chloroacetamide 4 (500 mg, 1.64 mmol) in thionyl chloride (20.5 mL) was heated at reflux for 1 h. The reaction mixture was then tempered to room temperature and evaporated to dryness in vacuo. Toluene (25 mL) was added and the resulting solution concentrated in vacuo.…”

“…1). [6][7][8] While performing a random screening for antibacterial activity (Table 1), we found that primary amines 2a and 2d displayed reasonable activity against S. aureus (MIC 50 = 17 and 95 lM, respectively). This result led us to perform a deeper study on the antibacterial activity of several related compounds and to evaluate their activity against several bacterial pathogens as well as in a preformed S. aureus biofilm in which cells are more resistant to existing antibiotics.…”