Sulfanilamide mechanism

Factor b above is discussed in Sections II, B, 1 II, B, 4 and II, C. A hydrogen-bonded structure such as 221 can account for the facile reaction of 5-bromouracil or for the unique, so-called hydrolyzability of carboxymethylthio-azines (237). The latter may also react via the intramolecular mechanism indicated in 136. The hydrogen-bonded transition state 238 seems a reasonable explanation of the fact that 3,4,6- and 3,4,5-trichloropyridazines react with glacial acetic acid selectively to give 3-pyridazinones while other nucleophiles (alkoxides, hydrazine, ammonia, or sulfanilamide anion) react at the 4- and 5-positions. In this connection, 4-amino-3,5-dichloro-pyridazine in liquid hydrazine gives (95°, 3hr, 60%yield)the isomer-... 

A. 3,5-Dichlorosulfanilamide. In a 2-1. round-bottomed flask, fitted with a two-holed stopper carrying a mechanical stirrer and a thermometer, are placed 50 g. (0.29 mole) of sulfanilamide and 500 ml. of water. About 50 ml. of a 500-ml. portion (approximately 6 moles) of pure concentrated hydrochloric acid is added, and the mixture is stirred until a clear solution results (Note 1). The remainder of the 500 ml. of hydrochloric acid is then added. If the internal temperature does not rise to 45°, the stirred solution should be warmed gently with a free flame until this temperature is reached. At this point 65 g. (59 ml., 0.58 mole) of 30% hydrogen peroxide (sp. gr. 1.108) is added and rapid stirring is initiated (Note 2). The heat of reaction causes a progressively faster rise in temperature. After 5 minutes the solution fills with a white precipitate which increases rapidly in amount and becomes delicately colored. When the temperature has reached 60°, about 10 minutes after adding the peroxide (Note 3), any further rise is preferably prevented by judicious cooling (Note 4). The reaction is allowed to proceed for 15... 

There has been much emphasis during the last few decades on bacteriostatic agents, which prevent or slow down the rate of bacterial growth and reproduction, so thal the natural protective mechanisms of the body can overcome the infection. These chemicals include the sulfonamide group, such as sulfathiazole, sulfadiazine, sulfanilamide, sulfasuxidine, and... 

Sulfanilamide cannot be used to make folic acid, but the bacterial enzymes cannot distinguish between sulfanilamide and p-aminobenzoic acid. The production of active folic acid is inhibited, and the organism stops growing. Sulfanilamide does not kill the bacteria, but it inhibits their growth and reproduction, allowing the body s own defense mechanisms to destroy the infection. 

Massive doses of sulfanilamide, as well as of other sulfonamides, caused alkaline diuresis as a side effect. From 1940 onwards, the mechanism of this side effect was further investigated it was confirmed that carbonic anhydrase inhibition was responsible for the diuresis. Presenting the whole story of the development of... 

The enzyme has been found in corals (Goreau, 1959), annelids (Clark, 1975), crustaceans (Costlow, 1959), molluscs (Wilbur, 1972, for references), and echinoderms (Heatfield, 1970). In all cases, sulfanilamide inhibitors of the enzyme added to the medium reduced the rate of calcification at least 50%, indicating that catalysis by carbonic anhydrase is required for the normal rate of mineralization. In theory, the reactions should occur without enzyme catalysis and this appears to be true. Various mechanisms of action have been suggested (e.g., Goreau, 1959 Istin and Girard, 1970b) but the exact role of carbonic anhydrase remains uncertain. 

Investigations into drugs suspected of causing cancer in humans have included aryl amine derivatives such as Paracetamol (17a)61 and phenacetin (17b). Metabolism of acetanilide (17c) yields aniline, and of 17b A-hydroxyphenacetin (18)62, in accord with views on mechanisms of toxicity as discussed in the next section. Tumor formation was induced in rats at excessively high dose levels and only under certain conditions. Drugs found to cause methemoglobinemia include antipyrine, acetanilide, sulfanilamide, sul-fapyridine, sulfathiazole, sulfonal and thional. 

Modified Hammett substituent constants (100) were used by Garrett et al. to describe the bacterostatic activities of a series of sulfanilamides (101). Hansch also used the homolytic substituent constants (ER) of Yamamoto and Otsu (102) in analyzing the activity of selected chloramphenicol derivatives (103). The resulting correlations led to the hypothesis of a free-radical mechanism of chloramphenicol action. Substituent measures of it electron charge density distributions (07 and ov)... 

It is not a true sulfanilamide-type drug substance, because it is not inhibited by PABA. Evidently, its antibacterial activity predominantly involves a mechanism which essentially differs from that of the true sulphanilamide-type compounds. 

The drug exerts its antibacterial spectum and mechanism of action almost identical to those of sulfanilamide. It is duly absorbed by the oral route. It has been observed that the absorption is more efficient with comparatively low than with high doses. It gets eliminated in the liver by acetylation. The half-life is 10 to 50 horn s and at least 8 days are normally needed to accomplish plateau concentrations. 

Woods DD. Relation of p-aminobenzoic acid to mechanism of action of sulfanilamide. Br J Exp Pathol 1940 21 74-90. 

The sulfonamides are antibacterial compounds that are sulfur-containing analogs of 7)-aminobenzoate. The simplest of these is sulfanilamide. What is the biochemical mechanism of sulfonamide action ... 

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