Reduction of 2-(p-Nitrobenzenesulfonamido)-Pyridine to Sulfapyridine in the Animal Body

Abstract

The substitution of a nitro for the amino group in sulfonamides, produces compounds with bactericidal activity in vivo 1 , 2 and in vitro. 3 Flynn and Kohl 4 have shown that p-nitrobenzenesulfonamide is capable of reduction in the body. We became interested in 2-(p-nitrobenzenesulfonamido)-pyridine† because of its apparent lack of toxicity on oral administration in spite of its antistreptococcal activity in vivo. 5 This finding was of sufficient interest to warrant a study of the fate of 2-(p-nitrobenzenesulfonamido)-pyridine after oral and intravenous administration in the dog, and following oral administration in man, rabbit, and the rat.

2-(p-Nitrobenzenesulfonamido)-pyridine is an insoluble, almost colorless compound which melts with decomposition at 192-3°C (corrected). On reduction with tin and HC1, sulfapyridine is obtained. The solubility in water is less than 1 mg % at 20°C.‡ This compound has also been described by Burton, et al., but they did not give any specific data except to state that due to its insolubility in vitro studies were difficult.

In order to study the fate of 2-(p-nitrobenzenesulfonamido)-pyridine in the animal body, the following procedure was used in determining this compound in the blood. Two cc of blood were diluted to 40 cc with distilled water and placed in a boiling water bath for 3 minutes. Seven drops of 1% acetic acid were added, and the tube was heated in the bath for another 3 minutes. After cooling, it was diluted to 50 cc, mixed, and filtered. Bratton and Marshall's method ⁶ was applied, using 9 cc filtrate and 1 cc 4 N HCI. Another portion of filtrate (18 cc plus 2 cc 4 N HCI) was shaken for 5 minutes with 0.5 g zinc dust to effect a reduction, filtered, and 10 cc of this filtrate was used for the color determination.