Benzylpyrimidine sulfonamides

B. Sulfonamides Including Benzylpyrimidine Sulfonamides L Physicochemical and Pharmacologic Properties... 

Benzylpyrimidine sulfonamides are based on the combination of a sulfonamide with trimethoprim or tetroxoprim. Chemically, trimethoprim is a 2,4-diamino-5-(3,4,5-trimethoxybenzyl)pyrimidine and has the following structural formula. 

Recently, mainly benzylpyrimidine sulfonamides have been applied in 5.9% of cases allergic reactions are described on the skin which are probably chiefly due to sulfonamide (Clark et al. 1980 Bernstein 1975). 

Trimethoprim, a trimethoxybenzylpyrimidine, selectively inhibits bacterial dihydrofolic acid reductase, which converts dihydrofolic acid to tetrahydrofolic acid, a step leading to the synthesis of purines and ultimately to DNA (Figure 46-2). Trimethoprim is about 50,000 times less efficient in inhibition of mammalian dihydrofolic acid reductase. Pyrimethamine, another benzylpyrimidine, selectively inhibits dihydrofolic acid reductase of protozoa compared with that of mammalian cells. As noted above, trimethoprim or pyrimethamine in combination with a sulfonamide blocks sequential steps in folate synthesis, resulting in marked enhancement (synergism) of the activity of both drugs. The combination often is bactericidal, compared with the bacteriostatic activity of a sulfonamide alone. 

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