The 4-aminoquinoline drugs, such as chloroquine (CQ), amodiaquine or piperaquine, are still commonly used for malaria treatment, either alone (CQ) or in combination with artemisinin derivatives. We previously described the excellent in vitro activity of a novel pyrrolizidinylmethyl derivative of 4-amino-7-chloroquinoline, namedMG3,againstP. falciparumdrug-resistant parasites. Here, we report the optimized and safer synthesis ofMG3, now suitable for a scale-up, and its additional in vitro and in vivo characterization.MG3is active against a panel ofP. vivaxandP. falciparumfield isolates, either alone or in combination with artemisinin derivatives. In vivoMG3is orally active in theP. berghei, P. chabaudi,andP. yoeliimodels of rodent malaria with efficacy comparable, or better, than that of CQ and of other quinolines under development. The in vivo and in vitro ADME-Tox studies indicate thatMG3possesses a very good pre-clinical developability profile associated with an excellent oral bioavailability, and low toxicity in non-formal preclinical studies on rats, dogs, and non-human primates (NHP). In conclusion, the pharmacological profile ofMG3is in line with those obtained with CQ or the other quinolines in use and seems to possess all the requirements for a developmental candidate.