Acids solubilizing moieties

A simple method of modifying promoiety acidity or basicity is to select other more acidic or basic ionizable functional groups. Convenient solubilizing moieties for ester prodrugs where the formulation pH should be between 3.5 and 5 would be those containing eithersulfonicKypid or tertiary amine ( ia > 8) functionalities. Quaternary ammonium-containing moieties, such as the choline esters mentioned earlier, would also be excellent choices for water-soluble derivatives if solubility was the only consideration (Anderson and Conradi, 1987). 

G. Attachment of the solubilizing moiety to carboxylic acid functionalities... 

Conversely, in the tricyclic antidepressant series, the passage from the basic imipramine to the acidic amineptine conserved the antidepressant properties. In other words, there are no general rules available for the selection of the most appropriate solubilizing moiety. It is therefore recommended, that for each new solubilization problem, acidic, basic and neutral solubilized versions of the parent molecule be prepared. 

Dihydroartemisinin ethers. A water-soluble derivative of artemisinin, the sodium salt of artesunic acid (the succinic half-ester derivative of dihydroartemisinin Fig. 35.2), can be administered by intravenous injection, a property that makes it especially useful in the treatment of advanced and potentially lethal cases of Plasmodium falciparum. Sodium artesunate is capable of rapidly reversing parasitaemia and causing the restoration to consciousness of the comatose cerebral malaria patient. The utility of sodium artesunate, however, is impaired by its poor stability due to the facile hydrolysis of the ester linkage. To overcome the ease of hydrolysis of the ester function in sodium artesunate, Lin et aO prepared a series of analogues in which the solubilizing moiety is joined to dihydroartemisinin by an... 

Those that are applied in solution with the developing agent should be of small molecular size. These couplers are normally soluble in basic media because of their intrinsic acidity. This property is lost in the coupler moiety of the corresponding dye. Therefore, the dye will be precipitated and will be non-wandering provided no other solubilizing group is present in the coupler or developer. 

---