Chlorzoxazone CAS 95-25-0

Introduction：Basic information about Chlorzoxazone CAS 95-25-0, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Chlorzoxazone Basic information

• Product Name: Chlorzoxazone
• Synonyms: Biomioran;Chlorzoxazon;component of Parafon Forte;Escoflex;Mioran;Miotran;Myoflexin;Myoflexine
• CAS: 95-25-0
• MF: C7H4ClNO2
• MW: 169.57
• EINECS: 202-403-9
• Product Categories: PARAFON;Oxazole&Isoxazole;Intermediates & Fine Chemicals;Pharmaceuticals
• Mol File: 95-25-0.mol

Chlorzoxazone Chemical Properties

• Melting point: 191-192 °C (lit.)
• density: 1.3771 (rough estimate)
• refractive index: 1.5557 (estimate)
• storage temp.: room temp
• solubility: DMSO: soluble50mg/mL, clear
• pka: pKa 8.3 (Uncertain)
• form: Powder
• color: white to off-white
• Water Solubility: 0.1 g/100 mL
• Merck: 14,2194
• Major Application: pharmaceutical
• InChI: InChI=1S/C7H4ClNO2/c8-4-1-2-6-5(3-4)9-7(10)11-6/h1-3H,(H,9,10)
• InChIKey: TZFWDZFKRBELIQ-UHFFFAOYSA-N
• SMILES: O1C2=CC=C(Cl)C=C2NC1=O
• LogP: 1.816 (est)
• CAS DataBase Reference: 95-25-0(CAS DataBase Reference)
• NIST Chemistry Reference: Chlorzoxazone(95-25-0)
• EPA Substance Registry System: Chlorzoxazone (95-25-0)

Safety Information

• Hazard Codes: Xn,T,Xi
• Risk Statements: 22-36/37/38-20/21/22
• Safety Statements: 26-36-24/25-37/39
• WGK Germany: 3
• RTECS: DM5250000
• Hazard Note: Toxic/Irritant
• TSCA: TSCA listed
• HazardClass: IRRITANT
• HS Code: 29349990
• Storage Class: 11 - Combustible Solids
• Hazard Classifications: Acute Tox. 4 Oral Eye Irrit. 2 Skin Irrit. 2 STOT SE 3
• Toxicity: LD50 in mice (mg/kg): 3650 orally, 380 i.p. (suspensions); 440 orally, 183 i.p. (solns of Na salt) (Hofrichter)

Chlorzoxazone Usage And Synthesis

Skeletal muscle relaxants

Chlorzoxazone is an orally active central skeletal muscle relaxant with its chemical structure being completely different with all the other muscle relaxants. It, mainly through acting on the central cerebral cortex and the spinal cord, inhibits the multi-synaptic reflection related to muscle spasms and produces muscle relaxation, further relieves the spasm caused pain and increase the flexibility of the muscles involved. Acetaminophen belongs to non-steroidal anti-inflammatory drugs and may mainly exert the analgesic and antipyretic effects through the inhibition of prostaglandin synthesis. Muscle relaxation studies through mouse traction test have demonstrated that the compound Chlorzoxazone showed a dose-dependent muscle relaxant effect with excellent protective effect on the strychnine-induced seizures in mice. The existence of paracetamol in the compound chlorzoxazone tablets can further enhance the effect of chlorzoxazone. Hot plate analgesic tests have showed the compound chlorzoxazone has a significant analgesic effect in a dose-dependent manner. It also has antagonism effect on the painful writhing of mice caused by antimony potassium tartrate in a good dose-response relationship. Test results have showed that acetaminophen and chlorzoxazone analgesic synergy.
This information is edited by Xiongfeng Dai from Chemicalbook.

Pharmacokinetics

This product can be completely absorbed by the digestive tract with the plasma concentration reaching peak at 1.5-2 hours. It is distributed in muscle, kidney, liver, brain and fat. After 6 hours, the drug concentration decreases significantly. Almost all of the goods can subject to in vivo catabolism with the elimination half-life being about 1 hour.
This information is edited by Xiongfeng Dai from Chemicalbook.

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.

Chlorzoxazone synthesis

Take 2, 5-dichloro-nitrobenzene as raw material; go through hydrolysis, reduction reaction to give 2-amino-4-chloro-phenol, followed by cyclization reaction in hydrochloric acid to obtain the finished product of Chlorzoxazone with the total yield being 84%.

Medicine interactions

When this product is used in combination with central inhibitory drugs such as phenothiazines and barbituric acid derivative and monoamine oxidase inhibition drugs, we should reduce the usage amount of this product.

Side effects

There may be occasionally mild drowsiness, dizziness, nausea, heart palpitations, weakness, abdominal pain and other reactions. This drug should be discontinued in case of allergic reactions. These adverse reactions are generally mild and may go away automatically or alleviated after stopping using this drug.

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.

Category

Toxic substances.

Toxicity grading

Highly toxic.

Acute toxicity

Oral-rat LD50: 763 mg/kg; Oral-Mouse LD50: 440 mg/kg.

Flammability and hazard properties

Thermal decomposition can release nitrogen oxides and chlorides smoke.

Storage characteristics

Treasury: ventilated, low temperature and dry; store it separately from food raw materials.

Extinguishing agent

Water, carbon dioxide, foam, powder.

Description

Chlorzoxazone is a muscle relaxant. It acts by blocking nerveimpulses or pain sensations that are sent to brain. Typically, itis used together with rest and physical therapy to treat skeletalmuscle conditions such as pain or injury. Chlorzoxazone,5-chloro-2-benzoxazolione, is synthesized by a heterocyclizationreaction of 2-amino-4-chlorophenol with phosgene.Skeletal muscle relaxants have conventionally been classifiedinto one group; however, they are actually a heterogeneousgroup of medications commonly used to treat two differenttypes of underlying conditions – spasticity from upper motorneuron syndromes and muscular pain or spasms fromperipheral musculoskeletal conditions. Medications classifiedas skeletal muscle relaxants are baclofen, carisoprodol,chlorzoxazone, cyclobenzaprine, dantrolene, metaxalone,methocarbamol, orphenadrine, and tizanidine. These drugsmay impair mental and/or physical abilities required fordriving vehicles. As a class, skeletal muscle relaxants havecentral nervous system (CNS)-related side effects: drowsiness,dizziness, decreased alertness, blurred vision, and ataxia.Their use has been associated with a twofold increase in therisk for motor vehicle crashes. Muscle relaxants are includedin the ‘Beers List’ of potentially inappropriate medicationsin older adults. Most muscle relaxants are poorly tolerated byelderly patients because they cause anticholinergic adverseeffects, sedation, and weakness. Although extremely uncommon,this compound may yield to idiosyncratic andunpredictable type of liver toxicity. The concomitant use ofalcohol or other CNS depressants may have an additive effect.Individuals on chlorzoxazone containing drugs should bemonitored for abnormal liver enzymes (e.g., aspartate transaminase(AST), alanine transaminase (ALT), alkaline phosphatase,bilirubin, etc.).

Description

Chlorzoxazone is a centrally acting muscle relaxant and activator of small and intermediate conductance calcium-activated potassium channels (EC₅₀s = 87 and 98 μM for K_Ca2.2 and K_Ca3.1, 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 .

Description

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 .

Chemical Properties

White to Off-White Solid

Originator

Paraflex ,McNeil, US ,1958

Uses

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.

Uses

Muscle relaxant (skeletal)

Uses

For the relief of discomfort associated with acute painful musculoskeletal conditions.

Definition

ChEBI: A member of the class of 1,3-benzoxazoles that is 1,3-benzoxazol-2-ol in which the hydrogen atom at position 5 is substituted by chlorine. A centrally acting muscle relaxant with sedative properties, it is used for the symptomatic treatment of painful musle spasm.

Manufacturing Process

A solution of 16.9 g (0.1 mol) of 2-amino-5-chlorobenzoxazole in 200 ml of 1N HCl is refluxed until precipitation is complete. The resulting solid is collected
by filtration, dissolved in 200 ml of 1 N NaOH and the solution extracted with50 ml of ether. Acidification of the alkaline solution gives a precipitate which ispurified by crystallization from acetone to give 2-hydroxy-5-chlorobenzoxazolemelting at 191° to 191.5°C.

Brand name

Paraflex (Ortho-McNeil).

Therapeutic Function

Muscle relaxant

General Description

Chlorzoxazone is a centrally active muscle relaxant used to treat painful muscle spasms linked to musculoskeletal disorders, such as fibrositis, bursitis, myositis, spondylitis, etc.
Pharmaceutical secondary standard for application in quality control. Provides pharma laboratories and manufacturers with a convenient and cost-effective alternative to the preparation of in-house working standards.

Biochem/physiol Actions

Chlorzoxazone is a skeletal muscle relaxant.

Synthesis

Chlorzoxazone, 5-chloro-2-benzoxazolione (15.3.15), is synthesized bya hetercyclization reaction of 2-amino-4-chlorphenol with phosgene.

Environmental Fate

Chlorzoxazone ismetabolized by the CYP1A2 and CYP2E1 microsomalenzymes to a toxic metabolite 6-hydroxychlorzoxazone.

Toxicity evaluation

Chlorzoxazone is a white to off-white solid. It is soluble in organic solventssuch as ethanol, methanol, and dimethyl sulfoxide (DMSO).

References

[1] P PEDARZANI M S. Molecular and cellular basis of small–and intermediate-conductance, calcium-activated potassium channel function in the brain.[J]. Cellular and Molecular Life Sciences, 2008, 65 20: 3196-3217. DOI: 10.1007/s00018-008-8216-x
[2] ZHENYU GAO. Cerebellar ataxia by enhanced Ca(V)2.1 currents is alleviated by Ca2+-dependent K+-channel activators in Cacna1a(S218L) mutant mice.[J]. Journal of Neuroscience, 2012, 32 44: 15533-15546. DOI: 10.1523/jneurosci.2454-12.2012
[3] F. WOODWARD HOPF . Chlorzoxazone, an SK-Type Potassium Channel Activator Used in Humans, Reduces Excessive Alcohol Intake in Rats[J]. Biological Psychiatry, 2011, 69 7: Pages 618-624. DOI: 10.1016/j.biopsych.2010.11.011

Chlorzoxazone Preparation Products And Raw materials

• Raw materials: 4-Chlorophenol-->4-CHLORO-2-NITROPHENOL-->Sodium hydroxide-->Zoxazolamine-->Hydrochloric acid
• Preparation Products: 1-Phenyltetrazole-5-thiol-->3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazolone