3 Molecular Modification in the Development of Newer Anti-infective Agents
Downloaded by UNIV OF CALIFORNIA SANTA CRUZ on March 10, 2013 | http://pubs.acs.org Publication Date: January 1, 1964 | doi: 10.1021/ba-1964-0045.ch003
The Sulfa Drugs GERHARD ZBINDEN Research Division, Hoffmann-La Roche Inc., Nutley, N. J.
The — S O N < group has interesting functions in several areas of medicinal chemistry. Its most important application lies in the field of antibacterials, where derivatives of sulfanilamide maintain an important position. Thousands of congeners of the sulfonamide molecule have been prepared. The most fruitful changes were achieved by substitution on the N atom, which yielded compounds of higher chemotherapeutic activity. Although the antibacterial spectrum was not significantly broadened, many chemical properties were changed, which resulted in differences in pharmacological behavior—e.g., solubility of the sulfonamides and their metabolites, protein binding, speed and pathway of metabolism, tissue distribution, and mechanism of elimination. These and other factors determine toxicity, half life, and effectiveness of a sulfonamide and greatly influence its clinical usefulness. 2
1
omagk's (7) discovery that Prontosil protected mice against lethal infections and the findings of Fourneau and his group (8) that sulfanilamide was the chemotherapeutically active moiety of Prontosil initiated a
D with streptococci
SULFANILAMIDE
PRONTOSIL
most important breakthrough in modern drug research. No other drug, with the possible exception of barbituric acid, has been as extensively modified as sul25 In Molecular Modification in Drug Design; Schueler, F.; Advances in Chemistry; American Chemical Society: Washington, DC, 1964.
26
MOLECULAR MODIFICATION IN DRUG DESIGN Sulfanilamide
H
Sulfadiazine
2 -
