Sulfapyridine, structure

Sulfasalazine, balsalazide, and olsalazine contain 5-ASA bound by an azo (N=N) bond to an inert compound or to another 5-ASA molecule (Figure 62-8). In sulfasalazine, 5-ASA is bound to sulfapyridine in balsalazide, 5-ASA is bound to 4-aminobenzoyl-B-alanine and in olsalazine, two 5-ASA molecules are bound together. The azo structure markedly reduces absorption of the parent drug from the small intestine. In the terminal ileum and colon, resident bacteria cleave the azo bond by means of an azoreductase enzyme, releasing the active 5-ASA. Consequently, high concentrations of active drug are made available in the terminal ileum or colon. 

An inspection of the values of the parameter (e) (Table 1) shows that this parameter has always positive values for the systems investigated and depends on the natures of both the drug and cosolvent. Eor the solubilities of structurally related caffeine and theophyllene in aqueous A,A-dimethylformamide, the values of (e) are close to each other (45.2 and 42.8). However, the values of (e) for the stmcturally more different sulfonamides (sulfadiazine, sulfadimidine, sulfamethizole, sulfamethoxazole, sulfapyridine, sul-famethoxypyridazine, sulfanilamide, and sulfisomi-dine) in water/dioxane mixtures differ by a factor of two and even three for sulfamethizole. 

Most of the sulfa drugs possess the general structure (17), and many of the most useful compounds contain a heterocyclic nucleus. Important examples include sulfapyridine (18), sulfadiazine (19), sulfathiazole (20) and sulfamethoxazole (21) (Figure 3). Sulfapyridine... 

SAR of Sulfapyridine. The drug afforded a tremendous impetus to the study of the whole class ofN -heterocyclically modified and substituted structural analogues of sulphanilamide. 

Immunologic Cross-reactivity between sulfamethoxazole and sulfasalazine has been studied using in vitro lymphocyte transformation responses in five subjects with severe allergies to either drug (2 and 3 subjects respectively) [124 "]. In all cases lymphocyte transformation was positive to both sulfamethoxazole and sulfapyridine (a metabolite of sulfasalazine), but not to the related non-aromatic sulfonamides furosemide and hydrochlorothiazide. Cross-reactivity can occur between sulfonamide antibiotics and non-antibiotics when there is structural similarity. 

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