Optimization of Pyrimidinylguanidines as Antimalarial Agents

If new classes of compounds are not discovered and approved, many of today’s malaria treatments will become ineffective due to the emergence of resistance to current drugs.

The focus of this effort will be to discover a drug candidate from a molecular class of compounds that does not show resistance to known anti-malarials. This compound class, referred to as pyrimidinylguanidines, was tested in four human clinical trials in the mid-1940s resulting in the relief of malaria symptoms with no evidence of any serious side effects. No drug was ever launched from this class since they did not display superiority to the emerging and existing therapies at the time. Thus, a more potent compound in the same class has a good chance of being safe, not showing resistance to current drugs, and being effective, at doses typical for preventing and treating malaria.

The project will target improving the activity of this class of compounds that has been shown to be safe in human clinical trials, but has not been used extensively in people. In light of emerging resistance to many antimalarial drugs currently, it is prudent to fully investigate the therapeutic potential of this class of compounds.

Basic Science
Drug Resistance
Drug-based Strategies

Sep 2013 — Sep 2016

$882,000