Suzuki-Miyaura Cross-Coupling Reaction As The Key Step For The Synthesis Of Some New 4 '-Aryl And Alkyl Substituted Analogues Of Amodiaquine And Amopyroquine

A versatile methodology for the synthesis of some new 4-aminoquinoquinoline antimalarial drugs, using Csp(2)-Csp(2) and Csp(2)- Csp(3) Suzuki-Miyaura cross-coupling reactions as a key step, is presented. The proposed strategy allowed the synthesis of 26 new amodiaquine (AQ) and amopyroquine (ApQ) derivatives. These new compounds constitute the base of the development of a new library, designed in order to obtain derivatives that present not only improved antimalarial activity, but also a better stability towards bioactivation in potentially toxic metabolites. (c) 2007 Elsevier Ltd. All rights reserved.