Dexoxadrol and its bioisosteres: structure, synthesis, and pharmacological activity

Abstract

© 2020, Springer Science+Business Media LLC. The review addresses the complete anthology of the development and evolution of dexoxadrol derivatives comprising a class of highly efficient NMDA receptor antagonists. Main approaches to the synthesis of dexoxadrol and enantiomeric 1-(2-piperidyl)ethane-1,2-diols and their structural relationship with natural alkaloids from plants of the genera Conium and Astrogalus are considered. Data on biomolecular mechanisms of action of this type of compounds are summarized. The relationships between their chemical structure and biological activity are analyzed. Based on the revealed relationships, different pathways of targeted modifications of the chemical structures of dexoxadrol and its analogues are suggested, which would help in future in overcoming the limitations associated with this type of physiologically active compounds, such as insufficient affinity for the channel binding site of the NMDA-receptor ionophore complex, low hydrolytic stability, anticholinergic side effects, and the production of toxic metabolites. These modifications will make it possible to utilize in full measure the great pharmacological potential of this type of compounds.