ABSTRACT
Proguanil (N 1-[p-chlorophenyl]-N 5-iso-propyldiguanide) (Figure 183.1) was synthesized by Imperial Chemical Industries (ICI) just before the end of World War II as part of the company’s biguanide anti-malarial drug development program. It was more active than quinine against avian malaria and had a wider therapeutic index (Curd et al., 1945). Reports regarding its use in both prevention and treatment of malaria in humans started to appear a few years later (Covell et al., 1949; De Rook, 1949; Maegraith and Andrews, 1949). Unfortunately, there were also relatively early reports of proguanil resistance in both Plasmodium falciparum (Seaton and Adams, 1949) and Plasmodium vivax (Seaton and Lourie, 1949), and its use as an anti-malarial drug declined. Chemical structure of proguanil, chlorproguanil, and their active metabolites. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781315152110/08d8042d-9481-4a8d-8c27-9bd589f6de6b/content/fig183_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>
