Amide-controlled, one-pot synthesis of tri-substituted purines generates structural diversity and analogues with trypanocidal activity

Scientific Reports
Maria J Pineda de las Infantas y VillatoroJuan J Diaz-Mochon

Abstract

A novel one-pot synthesis of tri-substituted purines and the discovery of purine analogues with trypanocidal activity are reported. The reaction is initiated by a metal-free oxidative coupling of primary alkoxides and diaminopyrimidines with Schiff base formation and subsequent annulation in the presence of large N,N-dimethylamides (e.g. N,N-dimethylpropanamide or larger). This synthetic route is in competition with a reaction previously-reported by our group, allowing the generation of a combinatorial library of tri-substituted purines by the simple modification of the amide and the alkoxide employed. Among the variety of structures generated, two purine analogues displayed trypanocidal activity against the protozoan parasite Trypanosoma brucei with IC50 < 5 μM, being each of those compounds obtained through each of the synthetic pathways.

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Citations

Apr 21, 2018·Magnetic Resonance in Chemistry : MRC·Álvaro Lorente-MacíasMaría José Pineda de Las Infantas Villatoro
Jun 16, 2021·Archiv der Pharmazie·Álvaro Lorente-MacíasMaría J Pineda de Las Infantas

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Methods Mentioned

BETA
fluorescence microscopy
optical microscopy

Software Mentioned

Zen
GraphPad Prism5

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African trypanosomiasis, also known as sleeping sickness, is an insect-borne parasitic disease of humans and other animals. It is caused by protozoa of the species Trypanosoma brucei and almost invariably progresses to death unless treated. Discover the latest research on African trypanosomiasis here.