Synthesis and antimalarial activity in vitro of potential metabolites of ferrochloroquine and related compounds

In man, the two major metabolites of the antimalarial drug chloroquine (CQ) are monodesethylchloroquine (DECQ) and didesethylchloroquine (di-DECQ). By analogy with CQ, the synthesis and the in vitro tests of some amino derivatives of ferrochloroquine (FQ), a ferrocenic analogue of CQ which are presumed to be the oxidative metabolites of FQ, are reported. Desmethylferrochloroquine 1a and didesmethylferrochloroquine 2 would be more potent against schizontocides than CQ in vitro against two strains (HB3 and Dd2) of Plasmodium falciparum. Other secondary amino derivatives have been prepared and proved to be active as antimalarial agents in vitro, too. (C) 1999 Published by Elsevier Science Ltd. ALI rights reserved.