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Chlorzoxazone

HCID 2733
NotesReactions
Basic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
Substructure searchFind similar structures

Basic information

CAS
95-25-0
Standard SMILES
O=c1[nH]c2cc(Cl)ccc2o1
InChIKey
TZFWDZFKRBELIQ-UHFFFAOYSA-N
Molecular formula
C7H4ClNO2
Average molar mass
169.56 g/mol
Monoisotopic mass
168.9930561

Overview

Chlorzoxazone is 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 muscle spasm. It has a role as a sedative and a muscle relaxant. It is an organochlorine compound, a member of 1,3-benzoxazoles and a heteroaryl hydroxy compound.

Names & identifiers

Preferred name
Chlorzoxazone
IUPAC
5-chloro-3H-1,3-benzoxazol-2-one
English name
Chlorzoxazone
Molecular formula
C7H4ClNO2
Molecular weight
169.57

Names & synonyms

chlorzoxazone95-25-0Paraflex5-Chloro-2(3H)-benzoxazolone5-Chloro-2-benzoxazolone2(3H)-Benzoxazolone, 5-chloro-5-Chloro-2-benzoxazolinone5-ChlorobenzoxazolidoneParafon Forte DSC5-chloro-3H-1,3-benzoxazol-2-one5-Chloro-2-benzoxazolol5-Chloro-2-hydroxybenzoxazole
Show more names
Chloroxazone5-CHLOROBENZO[D]OXAZOL-2(3H)-ONEChlorzoxazonCHLOROZOXAZONEMioranorzoxazoneCLORZOXAZONEChlorzoxazone-13C,15N,D2
ChlorzoxaneParafonStrifon Forte Dsc2-Hydroxy-5-chlorobenzoxazoleChlorzoxazonumClorzoxazonaStrifon5-chlorobenzoxazolin-2-one

Database identifiers

CAS
95-25-0
PubChem CID
2733
DTXSID
DTXSID9022813
ChEMBL
CHEMBL1371

Properties

Computed structural properties

XLogP
1.8
Topological polar surface area
38.3 Ų
Hydrogen bond donors
1
Hydrogen bond acceptors
2
Rotatable bonds
0
Heavy atoms
11
Formal charge
0
Complexity
185

Experimental & physicochemical properties

DrugsPharmaceuticals -> Listed in ZINC15
LogP · 2 items

1.6

2.11

Solubility · 2 items

2.96e+00 g/L

>25.4 [ug/mL] (The mean of the results at pH 7.4)

Human Drugs · 3 items

FDA approved drugs -> Active ingredient

FDA approved drugs -> Active ingredient

Pharmaceuticals

Melting Point · 2 items

191-191.5

191.5 °C

Physical DescriptionSolid
Collision Cross Section126.64 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Physicochemical properties

Melting point
191 · 191-192 °C (lit.)

Safety & regulation

Safety information is for reference only and does not replace the supplier’s Safety Data Sheet (SDS), applicable regulations, or professional assessment.

GHS classification

GHS Classification · 4 items

Warning

H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 54 reports by companies from 11 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Hazard information

Other Safety InformationIMAP assessments - 2(3H)-Benzoxazolone, 5-chloro-: Human health tier I assessment
Hazard Classes and CategoriesAcute Tox. 4 (100%)

Toxicology

Hepatotoxicity · 1 item

There have been no adequate prospective studies demonstrating the rates ofALT or AST elevations on chlorzoxazone therapy. Rare instances of clinicalapparent liver disease due to chlorzoxazone have appeared, including fatalcases. While case reports have been few, in many instances chlorzoxazone wasclearly implicated; furthermore, a related muscle relaxant with similarstructure (zoxazolamine) was withdrawn from use in 1961, largely because ofhepatotoxicity. The usual latency period to onset of liver injury is 1 to 4weeks, and the pattern of disease is typically hepatocellular with markedelevations in ALT levels and jaundice, but minimal increases in alkalinephosphatase. Cholestatic enzyme elevations after exposure to chlorzoxazonehave also been described. Allergic manifestations (rash and fever) arecommon, particularly in cases with a short latency (Case 1); autoantibodiesare rare. Recovery is rapid once chlorzoxazone is stopped, but fatal caseshave been reported, with disease progression despite early discontinuationof the agent (Case 2). There is rapid recurrence of injury with reexposure,often accompanied by fever.

Chemistry & industry

Pharmacology

ATC Code · 2 items

M - Musculo-skeletal system

QM - Musculo-skeletal system

Protein Binding13-18%
Pharmacodynamics · 1 item

Chlorzoxazone is a centrally-acting agent for painful musculoskeletal conditions. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex a.c. involved in producing and maintaining skeletal muscle spasm of varied etiology. The clinical result is a reduction of the skeletal muscle spasm with relief of pain and increased mobility of the involved muscles.

Mechanism of Action · 1 item

Chlorzoxazone inhibits degranulation of mast cells, subsequently preventing the release of histamine and slow-reacting substance of anaphylaxis (SRS-A), mediators of type I allergic reactions. Chlorzoxazone also may reduce the release of inflammatory leukotrienes. Chlorzoxazone may act by inhibiting calcium and potassium influx which would lead to neuronal inhibition and muscle relaxation. Data available from animal experiments as well as human study indicate that chlorzoxazone acts primarily at the level of the spinal cord and subcortical areas of the brain where it inhibits multisynaptic reflex arcs involved in producing and maintaining skeletal muscle spasm

Metabolism/Metabolites · 2 items

Chlorzoxazone is rapidly metabolized in the liver and is excreted in the urine, primarily in a conjugated form as the glucuronide.

Chlorzoxazone has known human metabolites that include 6-Hydroxychlorzoxazone.

FDA Pharmacological Classification · 6 items

H0DE420U8G

CHLORZOXAZONE

Physiologic Effects [PE] - Centrally-mediated Muscle Relaxation

Established Pharmacologic Class [EPC] - Muscle Relaxant

Chlorzoxazone is a Muscle Relaxant. The physiologic effect of chlorzoxazone is by means of Centrally-mediated Muscle Relaxation.

CHLORZOXAZONE

Related reactions

19 records
New reaction record
HRID 195055 reaction equation
HRID 195055As reactantTraining data from https://doi.org/10.1039/C8SC04228D (6/10)
HRID 270113 reaction equation
HRID 270113As reactantuspto-grants-2008_11
HRID 355036 reaction equation
HRID 355036As reactantuspto-grants-1983_03
HRID 358418 reaction equation
HRID 358418As reactantuspto-grants-1984_08
HRID 362462 reaction equation
HRID 362462As reactantuspto-grants-1999_02
HRID 650048 reaction equation
HRID 650048As reactantuspto-grants-2001_08
HRID 858159 reaction equation
HRID 858159As reactantuspto-grants-2006_12
HRID 986673 reaction equation
HRID 986673As reactantuspto-grants-1987_12
Page 1 of 3

Compound notes

Loading…

On this pageBasic informationOverviewNames & identifiersPropertiesSafety & regulationChemistry & industryRelated reactionsCompound notes
ChEBI
CHEBI:3655
UNII
H0DE420U8G
EC Number
202-403-9
Nikkaji
J3.950K
Density
1.3771 · 1.3771 (rough estimate)
refractive index
1.5557 · 1.5557 (estimate)
storage temp.
room temp
solubility
50 mg/mL, · DMSO: soluble50mg/mL, clear
form
Powder
pka
8.3 · pKa 8.3 (Uncertain)
color
white to off-white
Water Solubility
0.1 g/100 · 0.1 g/100 mL
Merck
14 · 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 · 1.816 (est)
CAS DataBase Reference
95 · 95-25-0(CAS DataBase Reference)
EWG's Food Scores
1 · 1
FDA UNII
0 DE420U8G · H0DE420U8G
NCI Drug Dictionary
chlorzoxazone
ATC code
3 BB03 · M03BB03
NIST Chemistry Reference
Chlorzoxazone(95-25-0)
EPA Substance Registry System
Chlorzoxazone (95-25-0)
UNSPSC Code
41116107 · 41116107
NACRES
77 · NA.77
Symbol(GHS)
7 · GHS07
Signal word
Warning
Hazard statements
302 · H302-H315-H319-H335
Precautionary statements
261 · P261-P264-P270-P301+P312-P302+P352-P305+P351+P338
target organs
Respiratory system
Hazard Codes
Xn,T,Xi
Risk Statements
22 · 22-36/37/38-20/21/22
Safety Statements
26 · 26-36-24/25-37/39
WGK Germany
3 · 3
RTECS
5250000 · DM5250000
Hazard Note
Toxic/Irritant
TSCA
TSCA listed
HazardClass
IRRITANT
HS Code
29349990 · 29349990
Storage Class
11 · 11 - Combustible Solids
Hazard Classifications
4 OralEye · Acute Tox. 4 OralEye Irrit. 2Skin Irrit. 2STOT SE 3
Toxicity
50 in · LD50 in mice (mg/kg): 3650 orally, 380 i.p. (suspensions); 440 orally, 183 i.p. (solns of Na salt) (Hofrichter)
Drug Induced Liver Injury · 6 items

Drug Induced Liver Injury Rank (DILIrank 2.0)

Chlorzoxazone

vMost-DILI-concern

8

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

Safety data

wgk
3
tsca
TSCA listed
rtecs
DM5250000
hs_code
29349990
Toxicity
LD50 in mice (mg/kg): 3650 orally, 380 i.p. (suspensions); 440 orally, 183 i.p. (solns of Na salt) (Hofrichter)
risk_code
22-36/37/38-20/21/22
Signal word
Warning
Symbol(GHS)
GHS07
hazard_code
Xn,T,Xi
hazard_note
Toxic/Irritant
safety_code
26-36-24/25-37/39
hazard_class
IRRITANT
Storage Class
11 - Combustible Solids
target organs
Respiratory system
Hazard statements
H302-H315-H319-H335
Hazard Classifications
Acute Tox. 4 OralEye Irrit. 2Skin Irrit. 2STOT SE 3
Precautionary statements
P261-P264-P270-P301+P312-P302+P352-P305+P351+P338
MeSH Pharmacological Classification · 1 item

A heterogeneous group of drugs used to produce muscle relaxation, excepting the neuromuscular blocking agents. They have their primary clinical and therapeutic uses in the treatment of muscle spasm and immobility associated with strains, sprains, and injuries of the back and, to a lesser degree, injuries to the neck. They have been used also for the treatment of a variety of clinical conditions that have in common only the presence of skeletal muscle hyperactivity, for example, the muscle spasms that can occur in MULTIPLE SCLEROSIS. (From Smith and Reynard, Textbook of Pharmacology, 1991, p358)

Absorption, Distribution and ExcretionChlorzoxazone is rapidly metabolized and is excreted in the urine, primarily in a conjugated form as the glucuronide.
Cellular LocationsMembrane

Uses & manufacturing

Use ClassificationPharmaceuticals
General Manufacturing Information2(3H)-Benzoxazolone, 5-chloro-: ACTIVE
Applications · 8 items

UsesIt 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.

DescriptionChlorzoxazone 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.).

DescriptionChlorzoxazone 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 .

DescriptionChlorzoxazone (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 .

UsesChlorzoxazone 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.

UsesMuscle relaxant (skeletal)

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

General DescriptionChlorzoxazone 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.

Upstream & downstream products

Upstream raw materials

4-CHLORO-2-NITROPHENOL4-ChlorophenolSodium hydroxideZoxazolamineHydrochloric acid

Downstream products

1-Phenyltetrazole-5-thiol3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2(3H)-benzoxazolone

Suppliers119 total

国药集团化学试剂有限公司86-21-63210123 · [email protected]
北京华美互利生物化工010-56205725 · [email protected]
梯希爱(上海)化成工业发展有限公司021-67121386 · [email protected]
上海阿拉丁生化科技股份有限公司400-6206333 13167063860 · [email protected]
盐城通铭生物科技有限公司15195160625 · [email protected]
艾吉析科技(上海)有限公司17717235263 · [email protected]
INTATRADE GmbH+49 3493/605464 · [email protected]
湖北海克斯生化有限公司17362916295; 17362916295 · [email protected]
南京世洲生物科技有限公司025-025-85560043 17301488900 · [email protected]
上海赛可锐生物科技有限公司021-58000709 13120558703 · [email protected]
Jai Radhe Sales+(91)-(79)-26431096/65255722 · [email protected]
Aladdin Scientific[email protected]
Syntechem Co.,Ltd[email protected]
武汉易泰科技有限公司上海分公司18930552037 · [email protected]
大连美仑生物技术有限公司0411-62910999 13889544652 · [email protected]
阿法埃莎(中国)化学有限公司400-6106006 · [email protected]
太原市瑞和丰科贸有限公司+86 351 7031519 · [email protected]
安耐吉化学&3A(安徽泽升科技股份有限公司)400-0056266 · [email protected]
北京绿百草科技发展有限公司010-61136123 · [email protected]
Pure Chemistry Scientific Inc.001-857-928-2050 or 1-888-588-9418 · [email protected]
上海泰坦科技股份有限公司4006009262 13023226327 · [email protected]
MedChemexpress LLC021-58955995 · [email protected]
上海瀚香生物科技有限公司177-54423994 17754423994 · [email protected]
上海稳同科技有限公司02151600108 13062666369 · [email protected]
孝感深远化工有限公司15527621225; 15527621225 · [email protected]
大赛璐药物手性技术(上海)有限公司021-50460086-9 15921403865 · [email protected]
玛雅试剂+86 (573) 82222445 (0)18006601000 452520369 · [email protected]
四川库利南科技有限公司400-1166-196 18981987031 · [email protected]
天津希恩思生化科技有限公司400 638 7771 · [email protected]
河南多贝化工有限公司0370-2785118 17550508557 · [email protected]
斯百全化学(上海)有限公司021-021-021-67601398-809-809-809 15221380277 · [email protected]
TargetMol 中国(陶术生物)400-821-0310 15002144251 · [email protected]
深圳菲斯生物科技有限公司0755-83725681-603
赛默飞世尔科技(中国)有限公司800-810-5118 · [email protected]
北京伊诺凯科技有限公司400-810-7969 010-59572699 · [email protected]
TCI AMERICA800-4238616 · [email protected]
TOKYO CHEMICAL INDUSTRY CO., LTD.03-36680489 · [email protected]
TCI Europe320-37350700 · [email protected]
成都思天德生物科技有限公司028-83243028 19136088901 · [email protected]
Clearsynth Labs Limited+91-22-26355700 · [email protected]
广州爱纯医药科技有限公司020-39119399 18927568969 · [email protected]
南京生利德生物科技有限公司025-57798810 18652991625 · [email protected]
上海陶素生化科技有限公司021-33632979 · [email protected]
湖北威德利化学试剂有限公司186-02735115 18602735115 · [email protected]
北京环宇世纪化学科技有限公司hysj_bj.com
上海湄水化工科技有限公司021-60549325 18616193163
HBCChem, Inc.+1-510-219-6317 · [email protected]
上海石洋化工有限公司021-56795766 · [email protected]
四川省维克奇生物科技有限公司028-81700200 18116577057 · [email protected]
成都零六生物科技有限公司400-1166-196 13458535857 · [email protected]
Additional notes · 1 item

DefinitionChEBI: 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 mus le spasm.