A case study---oxamniquine

The above tactics need not necessarily be used in the order given. We shall see this in the following example—the development of oxamniquine (Fig. 7.31). 

Oxamniquine is an important Third World drug used in the treatment of schistosomiasis (bilharzia). This disease affects an estimated two hundred million people and is contracted by swimming or wading in infected water. The disease is carried by a snail which can penetrate human skin and enter the blood supply. There, it produces eggs which become trapped in organs and tissues, and this in turn leads to the symptoms of the disease. 

The first stage in the development of oxamniquine was to find a lead compound, and so a study was made of compounds which were active against the parasite. The tricyclic structure lucanthone (Fig. 7.32) was chosen. It was known to be effective against some forms of the disease, but it was also toxic and had to be injected at regular intervals to remain effective. Therefore, the goal was to increase the activity of the drug, broaden its activity, reduce side-effects, and make it orally active. 

Having found a lead compound, it was decided to try simplifying the structure to see 

It was now reasoned that the p-aminoethylamino side-chain was important to receptor binding and would adopt a particular conformation in order to bind efficiently. This conformation would only be one of the many conformations which are available to a flexible molecule such as mirasan and so there would only be a limited chance of it being adopted at any one time. 

---