80573-04-2

Basic information

• Product Name: Balsalazide
• Synonyms: 5-((4-(((2-carboxyethyl)amino)carbonyl)phenyl)azo)-2-hydroxy-benzoicaci(e;BALSALZIDE DISODIUM;BALSALAZIDE SODIUM;BALSALAZIDE;balsalazido;(E)-5-[[4-[[(2-Carboxyethyl)amino]-carbonyl]phenyl]azo-2-hydroxybenzoic acid;BALSALAZIDE DISODIUM SALT;Benzoic acid, 5-((1E)-(4-(((2-carboxyethyl)amino)carbonyl)phenyl)azo)-2-hydroxy-
• CAS NO: 80573-04-2
• Molecular Formula: C17H15N3O6
• Molecular Weight: 357.32
• EINECS: 1312995-182-4
• Product Categories: Active Pharmaceutical Ingredients;Intermediates & Fine Chemicals;Pharmaceuticals;Amines;Aromatics;API
• Mol File: 80573-04-2.mol
• Article Data: 5

Chemical Properties

• Melting Point: 254-255?C
• Boiling Point: 729.6±60.0 °C(Predicted)
• Appearance: yellow solid
• Density: 1.44 g/cm³
• Vapor Pressure: 0Pa at 20℃
• Refractive Index: 1.649
• Storage Temp.: -20°C Freezer
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 2.97±0.10(Predicted)
• CAS DataBase Reference: Balsalazide(CAS DataBase Reference)
• NIST Chemistry Reference: Balsalazide(80573-04-2)
• EPA Substance Registry System: Balsalazide(80573-04-2)

Safety Data

• Hazardous Substances Data: 80573-04-2(Hazardous Substances Data)

Usage

Description

Different sources of media describe the Description of 80573-04-2 differently. You can refer to the following data:
1. Colazide was launched in the UK for mild to moderate acute attacks of ulcerative colitis. It can be prepared by diazotization of 3-(4-aminobenzoylamino) propionic acid followed by condensation with salicylic acid. Colazide, an analogue of sulfasalazine, was found to be non-toxic and non-mutagenic in the Ames test. Once ingested the molecule releases a non-toxic fragment, 4-aminobenzoyl-β-alanine (poorly absorbed - 75% excretion in stool), and the active component 5- aminosalicylic acid (Mesalazine). The exact mechanism of action is not clearly understood but it is cytoprotective and has antiinflammatory properties. Other biological effects have been observed and include the following: (a) granulocyte activation is blocked, (b) there is a reduction in myeloperoxidase activity, and (c) a reduction in the release of arachidonic acid with a concomitant decrease in prostaglandin and leucotriene (as indicated by the lack of production of LTB4) production. It can behave as a reactive oxygen species (ROS) scavenger, inhibit PAF formation, reduce IL-1 production, and antagonize TNF and NK cells. While comparable in efficacy to sulfasalazine, Colazide removes the possibility of sulfasalazine side-effects, such as, agranulocytosis, hepatotoxicity and male infertility.
2. Balsalazide is a prodrug form of 5-aminosalicylic acid (5-ASA; ). It is cleaved by bacterial azoreductases in the intestinal lumen to release 5-ASA. Balsalazide (600 mg/kg per day) decreases IL-2 levels and increases IL-6 levels in the serum and colonic mucosa membrane, as well as decreases micro- and macroscopic colonic damage, in a rat model of colitis induced by 2,4-dinitrochlorobenzene (DNCB). Formulations containing balsalazide have been used in the treatment of ulcerative colitis.

Chemical Properties

Yellow Solid

Originator

Biorex (UK)

Uses

Different sources of media describe the Uses of 80573-04-2 differently. You can refer to the following data:
1. An analogue of Sulfasalazine, A prodrug of 5-Aminosalicylic Acid
2. An analogue of Sulfasalazine (S699084). A prodrug of 5-aminosalicylic acid where carrier molecule is 4-aminobenzoyl-β-alanine. Anti-inflammatory (gastrointestinal).
3. Balsalazide-d4 is an isotopically labelled analog of Balsalazide (B116300), which is an analogue of Sulfasalazine (S699084). A prodrug of 5-aminosalicylic acid where carrier molecule is 4-aminobenzoyl-β-alanine. Anti-inflammatory (gastrointestinal).

Definition

ChEBI: A monohydroxybenzoic acid consisting of 5-aminosalicylic acid (mesalazine) linked to 4-aminobenzoyl-beta-alanine via an azo bond.

Therapeutic Function

Antiinflammatory

Clinical Use

Treatment and maintenance of remission, in mild to moderate ulcerative colitis

Drug interactions

Potentially hazardous interactions with other drugs None known

Metabolism

Very little of an oral dose of balsalazide is absorbed via the upper gastrointestinal tract, and almost the entire dose reaches its site of action in the colon intact. It is broken down by the colonic bacterial flora into 5-aminosalicylic acid (mesalazine), which is active, and 4-aminobenzoylalanine, which is considered to be an inert carrier. Most of a dose is eliminated via the faeces, but about 25% of the released mesalazine is absorbed and acetylated. A small proportion of 4-aminobenzoylalanine is absorbed and acetylated by first-pass metabolism through the liver. The acetylated metabolites are excreted in the urine.

InChI:InChI=1/C17H15N3O6/c21-14-6-5-12(9-13(14)17(25)26)20-19-11-3-1-10(2-4-11)16(24)18-8-7-15(22)23/h1-6,9,19H,7-8H2,(H,18,24)(H,22,23)(H,25,26)/b20-12-

Upstream product

• 69-72-7 salicylic acid 
• 59642-21-6 N-(4-nitrobenzoyl)-beta-alanine 
• 122-04-3 4-nitro-benzoyl chloride 
• 7377-08-4 N-(4-aminobenzoyl)-B-alanine 

Relevant articles and documents

Identification of the subtype-selective Sirt5 inhibitor balsalazide through systematic SAR analysis and rationalization via theoretical investigations

We report here an extensive structure-activity relationship study of balsalazide, which was previously identified in a high-throughput screening as an inhibitor of Sirt5. To get a closer understanding why this compound is able to inhibit Sirt5, we initially performed docking experiments comparing the binding mode of a succinylated peptide as the natural substrate and balsalazide with Sirt5 in the presence of NAD+. Based on the evidence gathered here, we designed and synthesized 13 analogues of balsalazide, in which single functional groups were either deleted or slightly altered to investigate which of them are mandatory for high inhibitory activity. Our study confirms that balsalazide with all its given functional groups is an inhibitor of Sirt5 in the low micromolar concentration range and structural modifications presented in this study did not increase potency. While changes on the N-aroyl-β-alanine side chain eliminated potency, the introduction of a truncated salicylic acid part minimally altered potency. Calculations of the associated reaction paths showed that the inhibition potency is very likely dominated by the stability of the inhibitor-enzyme complex and not the type of inhibition (covalent vs. non-covalent). Further in-vitro characterization in a trypsin coupled assay determined that the tested inhibitors showed no competition towards NAD+ or the synthetic substrate analogue ZKsA. In addition, investigations for subtype selectivity revealed that balsalazide is a subtype-selective Sirt5 inhibitor, and our initial SAR and docking studies pave the way for further optimization.

Sustainable Synthesis of Balsalazide and Sulfasalazine Based on Diazotization with Low Concentrations of Nitrogen Dioxide in Air

Low concentrations of nitrogen dioxide, which arises as a side product from a range of industrial processes, can effectively be recycled through the diazotization of anilines. The studies reported herein now demonstrate that the removal of nitrogen dioxide from gas streams is even more effective when hydrophilic anilines are used as starting materials. The diazonium salts, which are obtained in this way in up to quantitative yields, can directly be employed in azo coupling reactions, thus opening up an attractive route to the industrially important group of azo compounds.

Safe process for the preparation of balsalazide

A process for the preparation of Balsalazide and its pharmaceutically acceptable salts wherein the reaction comprises: a. the intermediate N-(4-aminobenzoyl)-β-alanine is converted to N-(4-ammoniumbenzoyl)-β-alanine sulfonate salt using a sulfonic acid in