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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
Epimers of bicyclo[2.2.2]octan-2-ol derivatives with antiprotozoal activity
Christian Schlapper1, Werner Seebacher, Marcel Kaiser
1Institute of Pharmaceutical Sciences, Pharmaceutical Chemistry, Karl-Franzens-University, Universitätsplatz 1, A-8010 Graz, Austria.
Abstract:
(2SR,6RS,7RS)-4-Dialkylaminobicyclo[2.2.2]octan-2-ols and several of their esters have shown promising activity against the causative organisms for malaria and sleeping sickness. The base-catalyzed epimerization of the alcohols was carried out by different methods giving their (2RS,6RS,7RS)-isomers. Best results were obtained by the consecutive use of potassium tert-butoxide and sodium. The isomeric alcohols were converted to selected esters. All new compounds were tested for their activity against Trypanosoma brucei rhodesiense (STIB 900) and a multiresistant strain of Plasmodium falciparum. The antitrypanosomal activity and the cytotoxicity were in general increased. The most active antitrypanosomal agents were the benzoate 8b and the 4-chlorobenzoate 9b of the 4-pyrrolidino series. The nicotinate 10a and the isonicotinate 11a showed the highest antiplasmodial activities.
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Structure and Nomenclature of Ethers
Ethers are organic compounds with an ether functional group which is characterized by an oxygen atom connected to two — identical or different — alkyl, aryl, or vinyl groups. The C–O–C linkage in dimethyl ether — the simplest ether — has an approximately tetrahedral bond angle of 110.3 degrees. The oxygen atom is sp3- hybridized, with the C–O distance being about 140 pm.
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Based on their attached substituent groups, ethers can be classified into two...

