Artemisinins increasing water solubility

Since the first series of compounds were poorly soluble in water, the next crucial phase of the project set out to increase the water solubility of the drug candidates in order to increase absorption from the gastrointestinal tract. Further refinements led to a candidate that was not only well absorbed when administered orally to animals, but also had outstanding antimalarial profiles both in vitro and in vivo. In comparison to available semi-synthetic artemisinins, the drug candidate OZ 277 (Scheme 27) exhibits structural simplicity, an economically feasible and scalable synthesis, superior antimalarial activity and an improved pharmaceutical profile. The toxicological profiles are also acceptable and this drug candidate entered first into man studies during 2004. 

Artemisinin is a potent antimalarial drug belonging to the chemical class of sesquiterpenoid endoperoxide lactones. Its poor solubUity in water and organic phases has led to a focus on the development of derivatives towards increased solubility, metabohc and chemical stabUity and bioavailabihty [92]. A common feature of the first generation of artemisinin derivatives was the replacement of the ketone with bigger polar groups to form... 

---