General Description
Odorless white to pinkish crystals or purplish-tan powder. Aqueous solutions acidic (pH approximately 4.1 at 0.8 mg/L water) .
Reactivity Profile
5-AMINOSALICYLIC ACID(89-57-6) is incompatible with acids, acid chlorides, acid anhydrides, chloroformates and strong oxidizers.
Air & Water Reactions
Sensitive to moisture. Water insoluble.
Fire Hazard
Flash point data for this chemical are not available; however, 5-AMINOSALICYLIC ACID is probably combustible.
Description
Fisalamine is an intestinal metabolite of sulfasalazine useful in the treatment of
ulcerative colitis and to a lesser degree in the management of Crohn’s disease.
Administered as a suppository, it appears to lack the hypersensitivity-type side
effects of sulfasalazine.
Chemical Properties
Off-White Crystals
Originator
Radcliffe Infirmary (United Kingdom)
Uses
For the treatment of active ulcerative proctitis.
Uses
In manufacture of light-sensitive paper, azo and sulfur dyes.
Uses
peroxidase substrate
Uses
The active metabolite of Sulfasalazine (S699084). Anti-inflammatory (gastrointestinal).
Application
5-Aminosalicylic acid (5-ASA) has been used to synthesize 5-formyl-aminosalicylate-inulin to quantify its release during in vitro digestion and fermentation and compare the in vitro fermentation properties of the conjugated inulin to native inulin. It is also used in cell adhesion assay to study its effects on E-cadherin glycosylation and membranous turnover. This compound is used to evaluate its effects on the neutrophilic inflammation index (NII) phenotype to study the effectiveness of the high cholesterol diet-gut inflammation (HCD-GI) platform.
5-Aminosalicylic acid is a peroxidase substrate suitable for use in ELISA procedures. This substrate produces a soluble end product that is brown in color and can be read spectrophotometrically at 450 nm. The reaction may be stopped with 3 N NaOH and read at 550 nm.
Definition
ChEBI: A monohydroxybenzoic acid that is salicylic acid which is substituted by an amino group at the 5-position.
Preparation
Preparation by reduction of m-nitrobenzoic acid with Zn dust and HCl.
Manufacturing Process
Procedure A: To 5-nitrosalicylic acid potassium salt (55 g, 246 mmol) dissolved in water (200 mL) was added potassium hydroxide pellets to reach pH 11.5. To this solution 2 g of Raney nickel were added. The mixture was heated-up to reflux and hydrazine hydrate (40 mL, 80% in water, 64 mmol) was added dropwise during 3-4 hrs. The reflux was maintened until HPLC showed the disappearance of the starting material and the complete reduction of 5-nitrosalicylic acid (3-4 hrs). The hot mixture was filtered under nitrogen and the solution was collected. The solution was cooled to 40°C and the pH was adjusted to 2.3 by addition of 35% HCl aqueous solution. The precipitation of 5-aminosalicylic acid occurred. The solution was cooled at 0°C, and after standing at this temperature for 2 hr, the precipitate was filtered, washed with water, and dried at 60-70°C. 5-Aminosalicylic acid was obtained in 89% yield.
Procedure B: To 5-nitrosalicylic acid potassium salt (55 g, 246 mmol) dissolved in water (200 mL) was added potassium hydroxide pellets to reach pH 11.5. The solution was charged in a stainless steel autoclave and 2 g of Raney nickel are added. Hydrogen was introduced into the autoclave reaching a pressure of 8 atm. The mixture was heated-up to 100°C. The temperature was maintained until HPLC-test 5-aminosalicylic acid showed the disappearance of the starting material and the complete reduction of 5- aminosalicylic acid (6-8 hrs). Hydrogen was purged and replaced by nitrogen. The hot mixture was filtered under nitrogen, the filtrate was cooled to 40°C, and the pH was adjusted to 2.3 by addition of 35% HCl aqueous solution. The precipitation of the 5-aminosalicylic acid occurred. The solution was cooled at 0°C, and after standing at this temperature for 2 hr, the precipitate was filtered, washed with ion depleted water, and dried at 60-70°C.
Therapeutic Function
Antibacterial
Flammability and Explosibility
Nonflammable
reaction suitability
reaction type: solution phase peptide synthesis
Biochem/physiol Actions
5-Aminosalicylic acid (5-ASA) is a first-line medicine, used to treat inflammatory bowel diseases like ulcerative colitis (UC). It has a high-efficiency rate in maintenance and induction of remission. 5-ASA is an active component of sulfasalazine and also consists of the carbohydrate polymer, inulin. It might exhibit anti-oxidant activity to lessen tissue injury. 5-ASA is vital for the prevention of T cell activation and proliferation. It negatively regulates cyclooxygenase and lipoxygenase pathways and lowers the formation of prostaglandins and leukotrienes. 5-ASA stimulates the membranous expression of E-cadherin and boosts intercellular adhesion.
Clinical Use
Induction and maintenance of remission in ulcerative
colitis
Side effects
5-Aminosalicylic acid (5-ASA) is widely used to treat ulcerative colitis and is better tolerated than sulfadiazine. Common side effects of 5-ASA include nausea, vomiting, abdominal pain, headache, and rash. 5-ASA-induced myocarditis is a rare side effect with only a few case reports. 5-ASA-induced myocarditis usually occurs within 2-4 weeks of medication and causes chest pain and dyspnea. In addition, 5-ASA can aggravate bloody diarrhea in patients with Crohn's disease, which may be accompanied by decreased appetite or hair loss, and is generally uncommon.
Safety Profile
Poison by intraperitoneal route.Moderately toxic by ingestion. Human systemic effects byingestion: hypermotility, diarrhea, dermatitis, increasedbody temperature. When heated to decomposition it emitstoxic fumes of NOx.
Drug interactions
Potentially hazardous interactions with other drugs
None known
Metabolism
The absorbed part of mesalazine is almost completely
acetylated in the gut wall and in the liver to acetyl-5-
aminosalicylic acid.
The acetylated metabolite is excreted mainly in urine by
tubular secretion, with traces of the parent compound.
storage
4°C, protect from light, stored under nitrogen
Purification Methods
It crystallises as needles from H2O containing a little NaHSO3 to avoid aerial oxidation to the quinone-imine. The Me ester gives needles from *C6H6, m 96o, and the hydrazide has m 180-182o (from H2O). [Fallab et al. Helv Chim Acta 34 26 1951, Shavel J Amer Pharm Assoc 42 402 1953, Beilstein 14 IV 2058.]
