Chlorzoxazone

Base Information

• Chemical Name: Chlorzoxazone
• CAS No.: 95-25-0
• Deprecated CAS: 32850-84-3
• Molecular Formula: C7H4ClNO2
• Molecular Weight: 169.567
• Hs Code.: 29349990
• European Community (EC) Number: 202-403-9
• NSC Number: 756693,26189
• UNII: H0DE420U8G
• DSSTox Substance ID: DTXSID9022813
• Nikkaji Number: J3.950K
• Wikipedia: Chlorzoxazone
• Wikidata: Q3294630
• NCI Thesaurus Code: C28926
• RXCUI: 2410
• Pharos Ligand ID: 3TU93933C3XR
• Metabolomics Workbench ID: 42730
• ChEMBL ID: CHEMBL1371
• Mol file: 95-25-0.mol

Synonyms:Chlorzoxazone;Paraflex;Parafon;Parafon Forte DSC

Chemical Property of Chlorzoxazone

Chemical Property:

• Appearance/Colour: White to off-white solid
• Melting Point: 191-192 °C
• Refractive Index: 1.5557 (estimate)
• Boiling Point: 336.9 °C at 760 mmHg
• PKA: pKa 8.3 (Uncertain)
• Flash Point: 157.5 °C
• PSA: 46.26000
• Density: 1.486 g/cm³
• LogP: 2.18680
• Storage Temp.: -20°C Freezer
• Solubility.: DMSO: soluble50mg/mL, clear
• Water Solubility.: 0.1 g/100 mL
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 168.9930561
• Heavy Atom Count: 11
• Complexity: 185

Purity/Quality:

99% ^*data from raw suppliers

Chlorzoxazone, substrate for Cytochrome P450 2E ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, T, Xi
• Hazard Codes: Xn,T,Xi
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 26-36-24/25-37/39

MSDS Files:

SDS file from LookChem

Total 1 MSDS from other Authors

Useful:

• Drug Classes: Autonomic Agents: Muscle Relaxants, Central
• Canonical SMILES: C1=CC2=C(C=C1Cl)NC(=O)O2
• Recent ClinicalTrials: Pharmacokinetic and Bioequivalence Comparison of Baclofen and Chlorzoxazone Administered Individually or Concurrently
• Recent EU Clinical Trials: An open label, explorative pharmacokinetic trial, to investigate the Cytochrome (CYP) CYP3A4, - 2E1 and – 1A2 clearance in Obese – versus Non Obese Children by use of well-tested probes (midazolam, chlorzoxazone, caffeine)
• Indications: Chlorzoxazone is suitable for the treatment of various kinds of acute and chronic soft tissue (muscles, ligaments and fascia) sprain, contusion, muscle pain after exercise, pain caused by muscle strain and the muscle spasms caused by the central nervous system lesions as well as chronic fasciitis.
• Uses: It can be used as pharmaceutical intermediates. It can be used as central muscle relaxants, for being applied to a variety of soft tissue pain caused by chronic sprain, contusion and muscle strain as well as muscle spasms and pain caused by the central nervous system and so on. Chlorzoxazone is a benzoxazolone derivative that causes skeletal muscle relaxation and blocks spasticity in clinical studies. Chlorzoxazone enhances small and intermediate conductance calcium-activated potassium channels (EC50s = 87 and 98 μM for KCa2.2 and KCa3.1, respectively). The cytochrome P450 isoform CYP2E1 converts chlorzoxazone to 6-hydroxy chlorzoxazone . The urinary excretion of this 6-hydroxy metabolite is often used as a probe of CYP2E1 activity in studies of hepatotoxicity. For the relief of discomfort associated with acute painful musculoskeletal conditions.
• Description: Chlorzoxazone is a muscle relaxant. It acts by blocking nerve impulses or pain sensations that are sent to brain. Typically, it is used together with rest and physical therapy to treat skeletal muscle conditions such as pain or injury. Chlorzoxazone, 5-chloro-2-benzoxazolione, is synthesized by a heterocyclization reaction of 2-amino-4-chlorophenol with phosgene. Skeletal muscle relaxants have conventionally been classified into one group; however, they are actually a heterogeneous group of medications commonly used to treat two different types of underlying conditions – spasticity from upper motor neuron syndromes and muscular pain or spasms from peripheral musculoskeletal conditions. Medications classified as skeletal muscle relaxants are baclofen, carisoprodol, chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone, methocarbamol, orphenadrine, and tizanidine. These drugs may impair mental and/or physical abilities required for driving vehicles. As a class, skeletal muscle relaxants have central nervous system (CNS)-related side effects: drowsiness, dizziness, decreased alertness, blurred vision, and ataxia. Their use has been associated with a twofold increase in the risk for motor vehicle crashes. Muscle relaxants are included in the ‘Beers List’ of potentially inappropriate medications in older adults. Most muscle relaxants are poorly tolerated by elderly patients because they cause anticholinergic adverse effects, sedation, and weakness. Although extremely uncommon, this compound may yield to idiosyncratic and unpredictable type of liver toxicity. The concomitant use of alcohol or other CNS depressants may have an additive effect. Individuals on chlorzoxazone containing drugs should be monitored for abnormal liver enzymes (e.g., aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, bilirubin, etc.). Chlorzoxazone is a centrally acting muscle relaxant and activator of small and intermediate conductance calcium-activated potassium channels (EC50s = 87 and 98 μM for KCa2.2 and KCa3.1, respectively). In vivo, chlorzoxazone (10 mg/kg) decreases alcohol but not water intake in a dose-dependent manner and reduces the propensity for rapid initial alcohol intake in rats with intermittent, but not continuous, access to alcohol. Formulations containing chlorzoxazone have been used in the treatment of pain and stiffness caused by muscle spasm. This product is also available as an analytical reference standard . Chlorzoxazone (Item No. 25826) is an analytical reference standard categorized as a skeletal muscle relaxant. This product is intended for analytical forensic applications. This product is also available as a general research tool .

Technology Process of Chlorzoxazone

There total 53 articles about Chlorzoxazone which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 98.0%

chloroformic acid ethyl ester (541-41-3) + 2-hydroxy-5-chloro-aniline (95-85-2) → 5-chloro-2-benzoxazolinone (95-25-0)

Guidance literature:

chloroformic acid ethyl ester; 2-hydroxy-5-chloro-aniline; With sodium hydrogencarbonate; In water; at 0 - 20 ℃; for 0.5h;

With potassium carbonate; In water; at 55 - 60 ℃; for 2h; Reagent/catalyst; Solvent; Temperature;

Reference yield: 97.0%

1,1'-carbonyldiimidazole (530-62-1) + 2-hydroxy-5-chloro-aniline (95-85-2) → 5-chloro-2-benzoxazolinone (95-25-0)

Guidance literature:

In 2-methyltetrahydrofuran; for 1h; Inert atmosphere; Reflux;

Reference yield: 92.0%

S,S-bis(1-phenyl-1H-tetrazol-5-yl) dithiocarbonate (32276-00-9) + 2-hydroxy-5-chloro-aniline (95-85-2) → 1-Phenyl-1H-tetrazole-5-thiol (86-93-1) + 5-chloro-2-benzoxazolinone (95-25-0)

Guidance literature:

In acetonitrile; for 12h;

upstream raw materials:

N-(5-chlorosalicyl) hydroxamic acid

zoxazolamine

(5-chloro-2-hydroxy-phenyl)-carbamic acid ethyl ester

2-amino-4-chlorophenol hydrochloride

Downstream raw materials:

5-chloro-3-methyl-1,3-benzoxazol-2(3H)-one

2-amino-4-chloro-5-nitrophenol

2-hydroxy-5-chloro-aniline

5-chloro-3-[2-oxo-2-[4-(trifluoromethyl)phenyl]ethyl]-2-(3H)-benzoxazolone

Refernces

• 1、 Baxendale, Ian R.,Gambacorta, Guido. "Continuous-Flow Hofmann Rearrangement Using Trichloroisocyanuric Acid for the Preparation of 2-Benzoxazolinone". . . Retrieved 2022/02/01.
• 2、 -. "Method for preparing carbonyl heterocyclic compound". Paragraph 0036-0040; 0126-0131. . Retrieved 2020/03/25.