15722-48-2

Basic information

• Product Name: OLSALAZINE
• Synonyms: OLSALAZINE;3,3’-azobis(6-hydroxy-benzoicaci;3,3’-azobis(6-hydroxybenzoicacid);5,5’-azobis(salicylicacid);azodisal;c.i.mordantyellow5;Ph-CJ-91B;4,4'-Dihydroxyazobenzene-3,3'-dicarboxylic acid
• CAS NO: 15722-48-2
• Molecular Formula: C₁₄H₁₀N₂O₆
• Molecular Weight: 302.24
• EINECS: 1312995-182-4
• Mol File: 15722-48-2.mol
• Article Data: 4

Chemical Properties

• Melting Point: >300 °C(Solv: acetic acid (64-19-7); water (7732-18-5))
• Boiling Point: 443.29°C (rough estimate)
• Flash Point: 348.863 °C
• Appearance: /
• Density: 1.3578 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.6500 (estimate)
• PKA: 2.40±0.10(Predicted)
• Water Solubility: 11.49ug/L(25 oC)
• CAS DataBase Reference: OLSALAZINE(CAS DataBase Reference)
• NIST Chemistry Reference: OLSALAZINE(15722-48-2)
• EPA Substance Registry System: OLSALAZINE(15722-48-2)

Safety Data

• Hazardous Substances Data: 15722-48-2(Hazardous Substances Data)

Usage

Uses

Anti-inflammatory (gastrointestinal).

Indications

Olsalazine is approved for maintenance of remission of ulcerative colitis, but a commonly reported side effect is a paradoxical increase in diarrhea. The U. S. Food and Drug Administration (FDA) has approved balsalazide disodium (Colazal) as a treatment of mild to moderately active ulcerative colitis.

Definition

ChEBI: An azobenzene that consists of two molecules of 4-aminosalicylic acid joined by an azo linkage. A prodrug for mesalazine, an anti-inflammatory drug, it is used (as the disodium salt) in the treatment of inflammatory bowel disease.

Brand name

Dipentum (UCB).

Mechanism of action

Olsalazine is approved for maintenance of remission of ulcerative colitis, but a commonly reported side effect is a paradoxical increase in diarrhea. The U. S. Food and Drug Administration (FDA) has approved balsalazide disodium (Colazal) as a treatment of mild to moderately active ulcerative colitis.

Veterinary Drugs and Treatments

Olsalazine is used for treatment of dogs with chronic colitis that either cannot tolerate the adverse effects associated with sulfasalazine or the response to sulfasalazine has been ineffective.

InChI:InChI=1/C14H10N2O6/c17-11-3-1-7(5-9(11)13(19)20)15-16-8-2-4-12(18)10(6-8)14(21)22/h1-6,17-18H,(H,19,20)(H,21,22)/b16-15+

Synthetic route

olsalazine methyl ester (101351-60-4) → olsalazine (15722-48-2)

Conditions	Yield
With water; sodium hydroxide at 90 - 95℃; for 2h;	97.6%
With sodium hydroxide

3,3'-azo[bis(6-hydroxybenzoic acid)] disodium salt → olsalazine (15722-48-2)

Conditions	Yield
With hydrogenchloride In water at 20℃; for 0.0833333h; pH=Ca.0;	90%

2-chloro-5-nitrobenzoic acid (2516-96-3) → olsalazine (15722-48-2)

Conditions	Yield
With sodium hydroxide; zinc beim Erhitzen der erhaltenen 4.4'-Dichlor-azobenzol-dicarbonsaeure-(3.3') mit Kupfer und wss. Natronlauge auf 150grad;

5-Aminosalicylic Acid (89-57-6) → olsalazine (15722-48-2)

Conditions	Yield
With pyridine; chromium chloride bei der Diazotierung des erhaltenen Komplexes und anschliessenden Umsetzung mit Salicylsaeure;
Multi-step reaction with 3 steps 1: sulfuric acid / 75 - 80 °C 2: acetic acid / 20 °C 3: water; sodium hydroxide / 2 h / 90 - 95 °C View Scheme
Multi-step reaction with 4 steps 1: sulfuric acid / 75 - 80 °C 2: oxone||potassium monopersulfate triple salt / dichloromethane; water / 2 h / 20 °C 3: acetic acid / 20 °C 4: water; sodium hydroxide / 2 h / 90 - 95 °C View Scheme

6,6'-dihydroxy-3,3'-azo-di-benzoic acid diethyl ester → olsalazine (15722-48-2)

Conditions	Yield
With potassium hydroxide

salicylic acid (69-72-7) + diazotized. 6-chloro-3-amino-benzoic acid → olsalazine (15722-48-2)

Conditions	Yield
With sodium hydroxide; copper(I) sulfate; copper(II) sulfate at 140℃;

ethyl 5-amino-2-hydroxybenzoate (62773-65-3) → olsalazine (15722-48-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; hydrogen peroxide 2: aqueous KOH-solution View Scheme

methyl salicylate (119-36-8) → olsalazine (15722-48-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: NaNO2; aqueous ethanol 2: aq. NaOH solution View Scheme

5-Aminosalicylic Acid (89-57-6) + salicylic acid (69-72-7) → olsalazine (15722-48-2)

Conditions	Yield
Stage #1: 5-Aminosalicylic Acid With hydrogenchloride; sodium nitrite In water at 0 - 5℃; for 0.5h; Stage #2: salicylic acid With sodium hydroxide In water for 1h; Cooling with ice;
With hydrogenchloride; sodium nitrite In water at 0℃;

methyl 5-amino-2-hydroxybenzoate (42753-75-3) → olsalazine (15722-48-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid / 20 °C 2: water; sodium hydroxide / 2 h / 90 - 95 °C View Scheme
Multi-step reaction with 3 steps 1: oxone||potassium monopersulfate triple salt / dichloromethane; water / 2 h / 20 °C 2: acetic acid / 20 °C 3: water; sodium hydroxide / 2 h / 90 - 95 °C View Scheme

methyl 2-hydroxy-5-nitrobenzoate (17302-46-4) → olsalazine (15722-48-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid / 20 °C 2: water; sodium hydroxide / 2 h / 90 - 95 °C View Scheme

butanoic acid anhydride (106-31-0) + olsalazine (15722-48-2) → 3,3'-azobis(6-hydroxybenzoic acid)dibutyrate

Conditions	Yield
at 81 - 82℃; for 2h;	95.7%

olsalazine (15722-48-2) → C14H8N2O6(2-)*Ca(2+)

Conditions	Yield
With calcium(II) nitrate tetrahydrate; sodium hydroxide In water at 90℃; Reagent/catalyst; Solvent;	85.1%

4,4'-bipyridine (553-26-4) + zinc(II) nitrate hexahydrate + olsalazine (15722-48-2) + water (7732-18-5) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 3C14H6N2O6(4-)*6Zn(2+)*4H2O*4C3H7NO*3C10H8N2

Conditions	Yield
at 115℃; for 72h;	80%

olsalazine (15722-48-2) → C14H6N2O6(4-)*2Mg(2+)

Conditions	Yield
With magnesium(II) nitrate hexahydrate In ethanol; N,N-dimethyl-formamide at 120℃; for 24h; Sealed tube;	80%

3-aminopropyltriethoxysilane (919-30-2) + olsalazine (15722-48-2) → C23H31N3O8Si

Conditions	Yield
Stage #1: olsalazine With 1-hydroxy-pyrrolidine-2,5-dione; dicyclohexyl-carbodiimide In tetrahydrofuran at 20℃; for 20h; Inert atmosphere; Stage #2: 3-aminopropyltriethoxysilane In tetrahydrofuran for 24h; Inert atmosphere;	80%

1,3-dibutanoyloxy-2-propanol (17364-00-0) + olsalazine (15722-48-2) → C36H46N2O14

Conditions	Yield
Stage #1: 1,3-dibutanoyloxy-2-propanol; olsalazine With dmap In dichloromethane at 0℃; for 0.333333h; Stage #2: With 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In dichloromethane at 22 - 25℃; for 16h;	49.5%

cisplatin (15663-27-1) + olsalazine (15722-48-2) → C14H18N6O6Pt2

Conditions	Yield
With sodium carbonate; silver nitrate In N,N-dimethyl-formamide at 20℃; for 24h; Darkness;	49%

C26H34N4O5 (1259528-75-0) + olsalazine (15722-48-2) → C40H42N6O10 (1259528-76-1)

Conditions	Yield
Stage #1: olsalazine With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: C26H34N4O5 In N,N-dimethyl-formamide at 20℃; for 24h;	45%

olsalazine (15722-48-2) + acetic anhydride (108-24-7) → 6,6'-diacetoxy-3,3'-azo-di-benzoic acid

chromium potassium sulfate dodecahydrate + olsalazine (15722-48-2) → Cr(3+)*C14H7N2O6(3-)*2H2O={CrC14H7N2O6(H2O)2}

Conditions	Yield
In sodium hydroxide addn. of hot aq. soln. of chromium alum to boiling soln. of 5.5'-azosalicylic acid in aq. NaOH, boiling react.-soln. for 3 h;; pptn., washing with large amt. of hot H2O, drying at 70 °C;;

C36H40N4O5 (1259528-78-3) + olsalazine (15722-48-2) → C50H48N6O10 (1259528-72-7)

Conditions	Yield
Stage #1: olsalazine With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: C36H40N4O5 In N,N-dimethyl-formamide at 20℃; for 24h;

NapFFK (1259528-74-9) + olsalazine (15722-48-2) → 5-Aminosalicylic Acid (89-57-6) + C43H45N5O7 (1259528-71-6)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine / N,N-dimethyl-formamide / 0.25 h / 20 °C 1.2: 24 h / 20 °C 2.1: sodium dithionite / water / 1 h / 37 °C / pH 5 / aq. buffer View Scheme

NapFFK (1259528-74-9) + olsalazine (15722-48-2) → C50H48N6O10 (1259528-70-5)

Conditions	Yield
Stage #1: olsalazine With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 0.25h; Stage #2: NapFFK In N,N-dimethyl-formamide at 20℃; for 24h;

olsalazine (15722-48-2) + iron(II) chloride → C14H6N2O6(4-)*2Fe(2+)

Conditions	Yield
Stage #1: olsalazine; iron(II) chloride With methanol In N,N-dimethyl-formamide at 100℃; for 16h; Glovebox; Sealed tube; Stage #2: at 120℃; Glovebox; Sealed tube;

cobalt(II) nitrate hexahydrate + olsalazine (15722-48-2) → C14H6N2O6(4-)*2Co(2+)

Conditions	Yield
In ethanol; N,N-dimethyl acetamide; water at 100℃; for 24h; Sealed tube;

nickel(II) nitrate hexahydrate + olsalazine (15722-48-2) → C14H6N2O6(4-)*2Ni(2+)

Conditions	Yield
In ethanol; water at 100℃; for 24h; Sealed tube;

copper(II) nitrate pentahydrate + olsalazine (15722-48-2) → C14H6N2O6(4-)*2Cu(2+)

Conditions	Yield
In ethanol; water at 100℃; for 24h; Sealed tube;

zinc(II) nitrate hexahydrate + olsalazine (15722-48-2) → C14H6N2O6(4-)*2Zn(2+)

Conditions	Yield
In ethanol; N,N-dimethyl acetamide at 100℃; for 24h; Sealed tube;

olsalazine (15722-48-2) → C14H6N2O6(4-)*Ca(2+)*2H(1+)

Conditions	Yield
Stage #1: olsalazine With water; sodium hydroxide Stage #2: With calcium(II) nitrate tetrahydrate at 90℃;

Upstream product

• 17302-46-4 methyl 2-hydroxy-5-nitrobenzoate 
• 42753-75-3 methyl 5-amino-2-hydroxybenzoate 
• 89-57-6 5-Aminosalicylic Acid 
• 69-72-7 salicylic acid 
• 119-36-8 methyl salicylate 
• 62773-65-3 ethyl 5-amino-2-hydroxybenzoate 
• 101351-60-4 olsalazine methyl ester 
• 2516-96-3 2-chloro-5-nitrobenzoic acid 

Downstream Products

• 1259528-76-1 C₄₀H₄₂N₆O₁₀ 
• 1259528-70-5 C₅₀H₄₈N₆O₁₀ 
• 89-57-6 5-Aminosalicylic Acid 
• 1259528-71-6 C₄₃H₄₅N₅O₇ 
• 1259528-72-7 C₅₀H₄₈N₆O₁₀ 

Related news

Determination of mesalazine, a low bioavailability OLSALAZINE (cas 15722-48-2) metabolite in human plasma by UHPLC–MS/MS: Application to a pharmacokinetic study09/24/2019

Olsalazine sodium, salicylate derivative (prodrug) is effectively bioconverted to mesalazine (5-aminosalicylic acid; 5-ASA), which has an anti-inflammatory activity in ulcerative colitis. In this article, a novel highly sensitive and selective method was developed and validated to determine mesa...detailed

Degradation kinetics of metronidazole and OLSALAZINE (cas 15722-48-2) by bacteria in ascending colon and in feces of healthy adults09/08/2019

PurposeTo compare the degradation kinetics of metronidazole and olsalazine by the bacteria of ascending colon and the bacteria of feces of healthy adults.detailed

Full paperOld drug, new indication: OLSALAZINE (cas 15722-48-2) sodium reduced serum uric acid levels in mice via inhibiting xanthine oxidoreductase activity09/07/2019

Hyperuricemia, a long-term purine metabolic disorder, is a well-known risk factor for gout, hypertension and diabetes. In maintaining normal whole-body purine levels, xanthine oxidase (XOD) is a key enzyme in the purine metabolic pathway, as it catalyzes the oxidation of hypoxanthine to xanthine...detailed

Research paperEx vivo evaluation of degradation rates of metronidazole and OLSALAZINE (cas 15722-48-2) in distal ileum and in cecum: The impact of prandial state09/06/2019

PurposeEvaluate ex vivo the bacterial metabolism induced degradation rates of mesalamine (negative control), metronidazole and olsalazine in distal ileum and in cecum.detailed

On the encapsulation of OLSALAZINE (cas 15722-48-2) by β-cyclodextrin: A DFT-based computational and spectroscopic investigations09/05/2019

In this work, the supramolecular host-guest interaction of the prodrug Olsalazine (OLZ) and β-Cyclodextrin (β-CD) was examined experimentally and computationally. Experimentally, employing the UV–Vis spectroscopic method in aqueous media at various pH's, results obtained using the Benesi...detailed

Enzyme and PH responsive 5-flurouracil (5-FU) loaded hydrogels based on OLSALAZINE (cas 15722-48-2) derivatives for colon-specific drug delivery09/03/2019

Colon-specific drug delivery systems are efficient for increasing the availability of drugs at colon region and are desirable for the treatment of local diseases such as ulcerative colitis and colonic cancer. We synthesized an acryloyl chloride modified olsalazine (olsalazine-AC) as an azo cross...detailed

Relevant articles and documents

Double Drug Delivery Using Capped Mesoporous Silica Microparticles for the Effective Treatment of Inflammatory Bowel Disease

Silica mesoporous microparticles loaded with both rhodamine B fluorophore (S1) or hydrocortisone (S2), and capped with an olsalazine derivative, are prepared and fully characterized. Suspensions of S1 and S2 in water at an acidic and a neutral pH show negligible dye/drug release, yet a notable delivery took place when the reducing agent sodium dithionite is added because of hydrolysis of an azo bond in the capping ensemble. Additionally, olsalazine fragmentation induced 5-aminosalicylic acid (5-ASA) release. In vitro digestion models show that S1 and S2 solids are suitable systems to specifically release a pharmaceutical agent in the colon. In vivo pharmacokinetic studies in rats show a preferential rhodamine B release from S1 in the colon. Moreover, a model of ulcerative colitis is induced in rats by oral administration of 2,4,6-trinitrobenzenesulfonic acid (TNBS) solutions, which was also used to prove the efficacy of S2 for colitis treatment. The specific delivery of hydrocortisone and 5-ASA from S2 material to the colon tissue in injured rats markedly lowers the colon/body weight ratio and the clinical activity score. Histological studies showed a remarkable reduction in inflammation, as well as an intensive regeneration of the affected tissues.

Calcium Coordination Solids for pH-Triggered Release of Olsalazine

Calcium coordination solids were synthesized and evaluated for delivery of olsalazine (H4olz), an anti-inflammatory compound used for treatment of ulcerative colitis. The materials include one-dimensional Ca(H2olz)?4 H2O chains, two-dimensional Ca(H2olz)?2 H2O sheets, and a three-dimensional metal-organic framework Ca(H2olz)?2DMF (DMF=N,N-dimethylformamide). The framework undergoes structural changes in response to solvent, forming a dense Ca(H2olz) phase when exposed to aqueous HCl. The compounds Ca(H2olz)?x H2O (x=0, 2, 4) were each pressed into pellets and exposed to simulated gastrointestinal fluids to mimic the passage of a pill from the acidic stomach to the pH-neutral intestines. All three calcium materials exhibited a delayed release of olsalazine relative to Na2(H2olz), the commercial formulation, illustrating how formulation of a drug within an extended coordination solid can serve to tune its solubility and performance.