4-Aminosalicylic acid Chemical Properties

Melting point:

135-145 °C (lit.)

Boiling point:

276.03°C (rough estimate)

Density 

1.3585 (rough estimate)

refractive index 

1.5500 (estimate)

storage temp. 

Keep in dark place,Inert atmosphere,Room temperature

solubility 

1.69g/l

form 

Powder

pka

3.25(at 25℃)

color 

Colorless

PH

3.5 (1g/l, H2O, 20℃)

Water Solubility 

2 g/L (20 ºC)

Merck 

14,477

BRN 

473071

BCS Class

4/2

Stability:

Hygroscopic

CAS DataBase Reference

65-49-6(CAS DataBase Reference)

NIST Chemistry Reference

Aminosalicylic acid(65-49-6)

EPA Substance Registry System

4-Aminosalicylic acid (65-49-6)

Safety Information

Hazard Codes 

Xn,Xi,T

Risk Statements 

22-36-36/37/38-45-35-61

Safety Statements 

26-37/39-45-53-36-36/37/39

RIDADR 

UN 1789 8/PG 3

WGK Germany 

2

RTECS 

VO1225000

TSCA 

Yes

HS Code 

29225000

Hazardous Substances Data

65-49-6(Hazardous Substances Data)

Toxicity

LD50 orally in mice: 4 g/kg (Bavin)

MSDS

• Language:English Provider:PAS
• Language:English Provider:ACROS
• Language:English Provider:SigmaAldrich
• Language:English Provider:ALFA

4-Aminosalicylic acid Usage And Synthesis

Chemical Properties

beige powder

Originator

Pamisyl,Parke Davis,US,1948

Uses

Intended for use in Sigma Periodic Acid Staining Procedure, 395. Kit is intended for use with blood, bone marrow, tissue touch preparations or routine tissue sections. It is used for staining glycoproteins in polyacrylamide gels. Schiff's reagent is also sometimes used to dye organic tissues. It is been widely used for detection of a certain functional group in chemical solutions.

Uses

antimycobacterial antitubercular;NF-kB inhibitor.
4-Aminosalicylic acid (p-aminosalicylic acid, PAS), an antituberculosis drug, is a model active pharmaceutical ingredient to study salt and cocrystal formation in a multiple hydrogen-bonding functionality molecule with carboxylic acid, amine, and phenol groups.
It has also been used as a second line agent to sulfasalazine in people with inflammatory bowel disease such as ulcerative colitis and Crohn's disease.It is typically taken by mouth.

Uses

An antibiotic used to treat tuberculosis.

Definition

ChEBI: An aminobenzoic acid that is salicylic acid substituted by an amino group at position 4.

Indications

p-Aminosalicylic acid is a bacteriostatic that inhibits most tuberculous mycobacteria. In terms of tuberculostatic activity it is inferior to isoniazid and streptomycin. It is nephroand hepatotoxic, and is rarely used. A synonym of this drug is apacizin.

Application

4-Aminosalicylic acid (4-ASA) can be used in the synthesis of:
Azo derivatives of 4-ASA with anti-inflammatory effects.
Ammonium 4-aminosalicylate salt polymorphs which are used as pharmaceutical ingredients.
Salicylic acid-triazole analogs which are used as quorum sensing inhibitors against Pseudomonas aeruginosa.

Manufacturing Process

As described in US Patent 427,564, aminosalicylic acid may be prepared from m-aminophenol by heating with ammonium carbonate in solution under pressure.
Alternatively, aminosalicylic acid may be made from sodium p-aminosalicylate as described in US Patent 2,844,625 as follows: 196 grams of commercial sodium para-aminosalicylate (18.5% H2O) was dissolved in 196 ml of water and 150 ml of isopropanol. 6 grams of sodium bisulfite was dissolved in the solution and the solution filtered. While stirring and keeping the temperature between 25-31°C, seven grams of 85% formic acid and 27.5 grams of 95% sulfuric acid in 150 ml of water was added during 1 ? hours. The mixture was stripped 1 hour longer, cooled to 23°C and filtered. The filter cake was washed with 100 cubic centimeters of water, further washed with 100 cc of 25% isopropanol and 100 cc of water, and vacuum dried to constant weight at 45- 50°C. Weight of p-aminosalicylic acid was 76.5 grams (92.7% yield) exhibiting a bulk density of 47 cc/oz.

brand name

Parasal (Panray); Paser (Jacobus).

Therapeutic Function

Antitubercular

General Description

4-Aminosalicylic acid occurs as a white to yellowish white crystalline solid that darkens on exposure to light or air. It is slightly soluble in water but more soluble in alcohol. Alkali metal salts and the nitric acid salt are soluble in water, but the salts of hydrochloric acid and sulfuric acid are not. The acid undergoes decarboxylation when heated. An aqueous solution has a pH of approximately 3.2. PAS is administered orally in the form of the sodium salt, usually in tablet or capsule form. Symptoms of gastrointestinal irritation are common with both the acid and the sodium salt. Various enteric-coated dosage forms have been used in an attempt to overcome this disadvantage. Other forms that are claimed to improve gastrointestinal tolerance include the calcium salt, the phenyl ester, and a combination with an anion exchange resin (Rezi-PAS). An antacid such as aluminum hydroxide is frequently prescribed. The oral absorption of PAS is rapid and nearly complete, and it is widely distributed into most of the body fluids and tissues, with the exception of the CSF, in which levels are significantly lower.It is excreted primarily in the urine as both unchanged drug and metabolites.

Biological Activity

4-Aminosalicylic acid is an antimetabolite of p-aminobenzoic acid (PABA) that has antibacterial activity.It is active against streptomycin-sensitive and -resistant strains of M. tuberculosis (MICs = 0.78 and 0.39 μg/ml, respectively), an effect that can be reversed by PABA. 4-Aminosalicylic acid is an alternative substrate for mycobacterial dihydropteroate synthase (FolP1) and misincorporation into the folate pathway leads to accumulation of several folate-dependent metabolites including serine, homocysteine, dUMP, and AICAR, markers of folate pathway inhibition, in a concentration-dependent manner. It reverses manganese-induced increases in rat hippocampal levels of NOD-like receptor protein 3 (NLRP3), cleaved caspase-1, and phosphorylated p65, markers of NLRP3 inflammasome-dependent pyroptosis, when administered at a dose of 300 mg/kg. 4-Aminosalycilic acid is also a building block that has been used in the synthesis of luminescent lanthanide complexes. Formulations containing 4-aminosalicylic acid have been used in the treatment of tuberculosis.

Mechanism of action

p-aminosalicylic acid is thought to act as an antimetabolite interfering with the incorporation of p-aminobenzoic acid into folic acid. When coadministered with INH, PAS is found to reduce the acetylation of INH, itself being the substrate for acetylation, thus increasing the plasma levels of INH. This action may be especially valuable in patients who are rapid acetylators.

Safety Profile

Moderately toxic ingestion andother routes. An eye irritant. Mutation data reported.When heated to decomposition it emits toxic fumes ofNOx.

Synthesis

p-Aminosalicylic acid, 5-amino-2-hydroxybenzoic acid (34.1.22), is synthesized in a Kolbe reaction, which consists of direct interaction of m-aminophenol with potassium bicarbonate and carbon dioxide while heating at a moderate pressure of 5¨C10 atm.

Metabolism

p-aminosalicylic acid is extensively metabolized by acetylation of the amino group and by conjugation with glucuronic acid and glycine at the carboxyl group. It is used primarily in cases of resistance, retreatment, and intolerance of other agents and is available from the CDC.

Purification Methods

Crystallise the acid from EtOH. [Beilstein 14 IV 1967.]

4-Aminosalicylic acid(65-49-6)Related Product Information

• 3-Hydroxybenzoic acid
• Salicylic acid
• Butylparaben
• 4-Hydroxybenzoic acid
• 4-Aminobenzoic acid
• 4-Amino-3-hydroxybenzoic acid
• Methylparaben
• 5-Amino-o-cresol
• Acetylsalicylic acid
• Acetaminophen
• Methyl salicylate
• Glycine
• 4-Dimethylaminobenzoic acid
• 4-AMINOSALICYLIC ACID, NA SALT,4-AMINOSALICYLIC ACID SODIUM DIHYDRATE
• Methy-5-aminosalicylate
• 4-Aminophenylacetonitrile
• Sulfanilic acid
• 4-Aminophenol