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 Csp2–Csp2 and Csp2–Csp3 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.