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  • Methimazole
Name:Methimazole
CAS No:60-56-0

PRODUCT DESCRIPTION

【Name】
Methimazole
【CAS Registry number】
60-56-0
【Synonyms】
4-Imidazoline-2-thione,1-methyl- (6CI,7CI)
Imidazole-2-thiol, 1-methyl- (8CI)
1-Methyl-1H-imidazole-2-thiol
1-Methyl-2-mercapto-1H-imidazole
1-Methyl-4-imidazoline-2-thione
1-Methylimidazole-2-thiol
1-Methylimidazole-2-thione
Basolan
Danantizol
Mercaptazole
Mercazole
Mercazolyl
【EINECS(EC#)】
200-482-4
【Molecular Formula】
C4H6N2S (Products with the same molecular formula)
【Molecular Weight】
114.16
【Inchi】
InChI=1/C4H6N2S/c1-6-3-2-5-4(6)7/h2-3H,1H3,(H,5,7)
【Canonical SMILES】
CN1C=CNC1=S
【MOL File】
60-56-0.mol

Chemical and Physical Properties

【Appearance】
White Solid
【Density】
1.28 g/cm3
【Melting Point】
140-145℃
【Boiling Point】
280℃
【Flash Point】
47.4 °C
【Water】
soluble
【Solubilities】
soluble in water
【Color/Form】
LEAFLETS FROM ALCOHOL
WHITE TO PALE BUFF, CRYSTALLINE SUBSTANCE; STARCH-LIKE IN APPEARANCE & TO TOUCH
【HS Code】
29332990
【Storage temp】
Refrigerator
【Spectral properties】
MAX ABSORPTION (CHLOROFORM): 267 NM (LOG E= 4.23)
IR: 2:1062C (Aldrich Library of Infrared Spectra, Aldrich Chemical Co, Milwaukee, WI)
UV: 3-18 (Organic Electronic Spectral Data, Phillips et al, John Wiley & Sons, New York)
NMR: 8:30A (Aldrich Library of Mass Spectra, Aldrich Chemical Co, Milwaukee, WI)
UV max (0.1 N sulfuric acid): 211, 251.5 nm (E 593, 1528, 1%, 1cm).
【Computed Properties】
Molecular Weight:114.16884 [g/mol]
Molecular Formula:C4H6N2S
XLogP3:-0.3
H-Bond Donor:1
H-Bond Acceptor:1
Rotatable Bond Count:0
Tautomer Count:2
Exact Mass:114.025169
MonoIsotopic Mass:114.025169
Topological Polar Surface Area:47.4
Heavy Atom Count:7
Formal Charge:0
Complexity:119
Isotope Atom Count:0
Defined Atom Stereocenter Count:0
Undefined Atom Stereocenter Count:0
Defined Bond Stereocenter Count:0
Undefined Bond Stereocenter Count:0
Covalently-Bonded Unit Count:1
Feature 3D Acceptor Count:1
Feature 3D Donor Count:1
Feature 3D Ring Count:1
Effective Rotor Count:0
Conformer Sampling RMSD:0.4
CID Conformer Count:1

Safety and Handling

【Hazard Codes】
Xn:Harmful;
【Risk Statements】
R43;R62;R63
【Safety Statements 】
S36/37
【Safety】

Hazard Codes:?Xn 
Risk Statements: 43-62-63 
43: May cause sensitization by skin contact 
62: Possible risk of impaired fertility 
63: Possible risk of harm to the unborn child 
Safety Statements: 26-27-45-36/37 
26: In case of contact with eyes, rinse immediately with plenty of water and seek medical advice 
27: Take off immediately all contaminated clothing 
45: In case of accident or if you feel unwell, seek medical advice immediately (show label where possible) 
36/37: Wear suitable protective clothing and gloves 
WGK Germany: 3 
RTECS: NI8615000 
HS Code: 29332990 
Poison by subcutaneous route. Moderately toxic by ingestion and intraperitoneal routes. Human teratogenic effects. An experimental teratogen. Experimental reproductive effects. Questionable carcinogen with experimental neoplastigenic data. Human mutation data reported. An antithyroid drug. When heated to decomposition it emits very toxic fumes of NOx and SOx. See also MERCAPTANS.

【Skin, Eye, and Respiratory Irritations】
Rashes may follow high doses of methimazole (120 mg daily). Both major (agranulocytosis, hepatotoxicity) and minor (arthralgias, skin rash, gastric intolerance) adverse effects are not dose related.
【Formulations/Preparations】
...METHIMAZOLE, USP (1-METHYL-2-MERCAPTOIMIDAZOLE; TAPAZOLE), MARKETED IN 5- & 10-MG TABLETS.
【Exposure Standards and Regulations】
Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended; 21 U.S.C. 321-392).
【Protective Equipment and Clothing】
Rashes may follow high doses of methimazole (120 mg daily). Both major (agranulocytosis, hepatotoxicity) and minor (arthralgias, skin rash, gastric intolerance) adverse effects are not dose related.
【Specification】

General Information: As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. 
Extinguishing Media: Use water spray, dry chemical, carbon dioxide, or chemical foam.?
Handling: Avoid breathing dust, vapor, mist, or gas. Avoid contact with skin and eyes. Avoid ingestion and inhalation. Use only in a chemical fume hood. 
Storage: Store in a cool, dry place. Store in a tightly closed container.

【Octanol/Water Partition Coefficient】
log Kow = -0.34
【Report】

Reported in EPA TSCA Inventory.

【Disposal Methods】
SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

Use and Manufacturing

【Use and Manufacturing】
Methods of Manufacturing

PREPD BY TREATING AMINOACETALDEHYDE DIETHYL ACETAL WITH METHYL ISOTHIOCYANATE; FROM THIOCYANIC ACID & N-SUBSTITUTED AMINO ACETALS.
【Usage】
Methimazole is a thiourea antithyroid agent that prevents iodine organification, thus inhibiting the synthesis of thyroxine. Antihyperthyroid

Biomedical Effects and Toxicity

【Pharmacological Action】
- Agents that are used to treat hyperthyroidism by reducing the excessive production of thyroid hormones.
【Therapeutic Uses】
Antithyroid Agents
METHIMAZOLE IS APPROX 10 TIMES AS POTENT AS PROPYLTHIOURACIL & IS MORE PROMPT IN ELICITING ANTITHYROID RESPONSE. DRUG ALSO EXHIBITS MORE PROLONGED ACTION THAN PROPYLTHIOURACIL...
...USED IN TREATMENT OF HYPERTHYROIDISM...(1) AS DEFINITIVE TREATMENT, TO CONTROL DISORDER IN ANTICIPATION OF SPONTANEOUS REMISSION IN GRAVE'S DISEASE; (2) IN CONJUNCTION WITH RADIOIODINE, TO HASTEN RECOVERY WHILE AWAITING EFFECTS OF RADIATION; & (3) TO CONTROL DISORDER IN PREPN FOR SURGICAL TREATMENT. /ANTITHYROID DRUGS/
THERE ARE NO COMMERCIAL PREPN AVAIL FOR PARENTERAL USE IN RARE EVENT THAT TREATMENT CANNOT BE GIVEN BY MOUTH. FOR THIS EVENTUALITY & FOR EXPTL PURPOSES, FREELY WATER-SOL COMPD, METHIMAZOLE, CAN BE DISSOLVED IN SALINE SOLN & STERILIZED BY HEAT.
Methimazole /is/ indicated in the treatment of hyperthyroidism, including prior to surgery or radiotherapy, and as adjunct in the treatment of thyrotoxicosis or thyroid storm. Propylthiouracil may be preferred over methimazole for use in thyroid storm, since propylthiouracil inhibits peripheral conversion of thyroxine (T4) to triiodothyronine (T3). /Included in US product labeling/
【Biomedical Effects and Toxicity】
FOUR DAYS AFTER IV ADMIN OF (14)C-METHIMAZOLE TO RATS, RETENTION OF (14)C WAS GREATEST IN THYROID & ADRENALS; 76% OF DOSE HAD BEEN EXCRETED IN URINE & 6% IN FECES.
(14)C-METHIMAZOLE RADIOACTIVITY CONCENTRATES MORE IN THE THYROID THAN IN ANY OTHER TISSUE, WITH THYROID:PLASMA RATIO REACHING 62.5 AFTER 4 DAYS' CONTINUOUS DOSING.
COMPLETE ABSORPTION...FROM ORAL DOSES...DEMONSTRATED IN RATS. ...IS NEGLIGIBLY BOUND TO PLASMA PROTEINS &...EXHIBITS SINGLE-COMPARTMENT KINETICS EVEN AFTER IV DOSES. ...ATTRIBUTED TO FASTER TISSUE PENETRATION BY METHIMAZOLE DUE TO ITS HIGHER LIPID:WATER PARTITION COEFFICIENT.
BILIARY EXCRETION OF RADIOACTIVITY FROM...(35)S-METHIMAZOLE...AMOUNTED TO ONLY 21%...OF IV DOSES. BILIARY RADIOACTIVITY WAS ALMOST ENTIRELY DUE TO METABOLITES...
/ANTITHYROID DRUGS/ CROSS PLACENTA & CAN ALSO BE FOUND IN MILK. /ANTITHYROID DRUGS/
T/2...IN PLASMA...FOR METHIMAZOLE IS ABOUT 4-6 HR. THE DRUGS APPEAR TO BE CONCN IN THYROID, & METHIMAZOLE, DERIVED FROM METABOLISM OF CARBIMAZOLE, ACCUMULATES AFTER CARBIMAZOLE IS ADMIN.
T/2 OF...METHIMAZOLE...SHOWN TO BE SIGNIFICANTLY REDUCED FOLLOWING SINGLE ORAL DOSE TO HYPERTHYROID PATIENTS. T/2 OF...DRUG WAS LENGTHENED IN HYPOTHYROID PATIENTS.
PLACENTAL TRANSFER OF (35)S-METHIMAZOLE IN RATS DURING LATE PREGNANCY RAPIDLY REACHED FETAL-MATERNAL SERUM EQUILIBRIUM AFTER IV ADMIN. FETAL:MATERNAL RATIO LESS THAN 1. ORAL DOSES IN HUMAN GAVE SIMILAR RESULTS. LOCALIZATION IN HUMAN FETAL THYROID WAS OBSERVED.
Methimazole is rapidly absorbed from the GI tract following oral administration with peak plasma concentrations occurring within about 1 hour. Methimazole readily crosses the placenta and is distributed into milk in concentrations approximately equal to those in maternal serum. The drug is excreted in urine. In one study, about 12% of a dose was excreted in urine within 24 hours.

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