P-Aminosalicylic, acid

SALICYLIC ACID AND RELATED COMPOUNDS] (Vol 21) p-aminosalicylic acid [65-49-6]... 

The benzoic acid moiety common to many of the benzamides is prepared in straightforward manner from the methyl ether of p-aminosalicylic acid 141. Acylation on nitrogen (142) followed by chlorination gives intermediate 143 benzoic acid 144 is then obtained by removal of the acetyl group. Condensation of this acid with an aminopiperidine could be achieved by means of the mixed anhydride (prepared by reaction with ethyl chlonoformate), which affords clebopride (145). Reaction with 3-aminoquinuclidine (146) of the intermediate prepared from acid 144 with carbonyldiimidazole affords zacopride (147) [36]. 

CO2 124-38-9) see p-Aminosalicylic acid Gentisic acid Indecainide Lamotrigine Salicylic acid Troglitazone L-Tryptophan carbon disulfide... 

Elevations of serum transaminase concentrations generally are not correlated with the residual capacity of the liver to metabolize drugs, so these markers cannot be used directly as guides for residual metabolic capacity. Hepatically cleared TB drugs include isoniazid, rifampin, pyrazinamide, ethionamide, and p-aminosalicylic acid.39 Ciprofloxacin is about 50% cleared by... 

Fig. 20 Mean plasma concentrations of unchanged drug from 12 subjects following administration of four different preparations of p-aminosalicylic acid (PAS). Data were corrected to 70 kg of body weight and to a dose equivalent of 4 g of free acid. (From Ref. 24.).

T. Oguchi, Freezing of drug/additive binary systems II. Relationship between decarboxylation behavior and molecular states of p-aminosalicylic acid, Chem. Pharm. Bull., 37, 3088-3091 (1989). 

It is noteworthy that cyanoguanidine and p-aminosalicylic acid react in acidified boiling water with simultaneous decarboxylation [608), giving m-hydroxyphenylbiguanide instead of the expected l-(3-hydroxy-4-carboxyphenyl)biguanide. The decarboxylation under such mild conditions appears to be anomalous, since p-aminobenzoic acid [100) and its esters [97) do give the expected biguanides. 

In addition to drugs administered specifically to produce a metabolic effect, there are drug-related physiological changes that cause laboratory test abnormalities. Many drugs have been associated with the appearance of abnormal liver function tests in a fashion that simulates extrahepatic obstruction. These drugs include, among others, chlorpromazine, cinco-phen, methyltestosterone, thiouracil, p-aminosalicylic acid, sulfadiazine, reserpine, meprobromate, novobiocin, caffeine, and phenacemide (L7, L8, S6). 

Addition of ethyl acetate to a specimen having a transaminase activity of 47 units was responsible for the following increases in enzyme activity 10 mg/100 ml, 60 units 20 mg/100 ml, 77 units 40 mg/100 ml, 107 units and 80 mg/100 ml, 150 units. Transaminase activity in these specimens determined by another method ranged from 32 to 34 units (C7). Thus, when serum from patients with ketosis is assayed for aspartate aminotransferase activity by the diazo method, false elevations of activity may be recorded due to reaction of acetoacetic acid. In Table 11 are shown some values obtained by the diazo method and by an ultraviolet NADH NAD aspartate aminotransferase technique (B12). Examination of the medical records of these patients indicated that they were either diabetics who were in ketosis or individuals who were eating very poorly and had some degree of starvation ketosis. Similar elevations have been observed in patients receiving p-aminosalicylic acid (G6). 

Although the two forms of the enzyme have preferred substrates, there is overlap between them such that no substrate seems to be exclusively acetylated by one or the other. Some preferred NAT1 substrates are p-aminobenzoic acid and p-aminosalicylic acid and sulfanilamide, whereas preferred substrates for NAT2 include isoniazid, hydralazine, procainamide, and dapsone. 

Abbreviations-. PA BA, p-aminobenzoic acid PAS, p-aminosalicylic acid PA, procainamide SMZ, sulfamethazine. 

However, using "polymorphic" substrates with the isolated enzyme, no correlation could be found between Km and acetylator status only when "monomorphic" substrates (p-aminobenzoic acid and p-aminosalicylic acid) were used was this apparent (Table 5.15). It is notable that both these substrates are negatively charged at physiological pH. 

It should be noted that in the hamster the situation is the reverse, with p-aminobenzoic acid and p-aminosalicylic acid being polymorphically acetylated and sulfamethazine and procainamide monomorphically acetylated. 

Other Derivatives of SaUcylic Acid. p-Aminosalicylic acid and its salts have been used in the treatment of tuberculosis. / -Aminosalicylic add can be prepared by the caiboxylation of in-amiuoplienol. Metliylene-5,5-disalicylic acid, produced by heating two parts salicylic acid with 1-1.5 parts of 30-40 wt % formaldehyde in the presence of an add catalyst, is used as an intermediate in the production of bacitracin me thy le ne di salicy la te. 

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