Originator
Favistan ,Asta
Definition
ChEBI: Methimazole is a member of the class of imidazoles that it imidazole-2-thione in which a methyl group replaces the hydrogen which is attached to a nitrogen. It has a role as an antithyroid drug.
Manufacturing Process
2 Methods of preparation of thiamazole:
1. To 2,2-diethoxyethylamine methylisothiocyanate was added and mixed after then 1-(2,2-diethoxy-ethyl)-3-methylthiourea was obtained.
The reaction of the 1-(2,2-diethoxyethyl)-3-methylthiourea with sulfuric acid yield thiamazole.
2. 1,1-Diethoxyethane was treated by bromine in the presence CaCO3 and 2- bromo-1,1-diethoxyethane was obtained.
Then to the 2-bromo-1,1-diethoxyethane methylamine was added, mixed and reaction mixture was heated to 120°-130°C in autoclave. As the result (2,2- diethoxyethyl)methylamine was obtained.
(2,2-Diethoxyethyl)methylamine reacted with potassium thiocyanate in the presence of hydrochloric acid and give the thiamazole, yellow crystallic precipitate, melting point 144°-147°C.
Brand name
Tapazole (Jones);
Tapazole (King)
.
Therapeutic Function
Thyroid inhibitor
General Description
Methimazole, 1-methylimidazole-2-thiol (Tapazole), occurs as a white to off-white, crystallinepowder with a characteristic odor and is freely soluble inwater. A 2% aqueous solution has a pH of 6.7 to 6.9. It shouldbe packaged in well-closed, light-resistant containers.
Biochem/physiol Actions
Methimazole is a thiourea antithyroid agent that prevents iodine organification, thus inhibiting the synthesis of thyroxine.
Clinical Use
Methimazole is indicated in the treatment of hyperthyroidism.It is more potent than propylthiouracil. The side effectsare similar to those of propylthiouracil. As with otherantithyroid drugs, patients using this drug should be undermedical supervision. Also, like the other antithyroid drugs,methimazole is most effective if the total daily dose is subdividedand given at 8-hour intervals.
Synthesis
Methimazole, 1-methyl-2-imidazolthiol (25.2.5), is synthesized by reacting
aminoacetic aldehyde diethylacetal with methylisothiocyanate and subsequent hydrolysis
of the acetal group of the resulting disubstituted urea derivative 25.2.4 by a solution
of sulfuric acid, during which a simultaneous cyclization reaction takes place, forming the
imidazole ring of the desired methimazole .
Veterinary Drugs and Treatments
Methimazole is considered by most clinicians to be the agent
of choice when using drugs to treat feline hyperthyroidism.
Propylthiouracil has significantly higher incidences of adverse
reactions
when compared to methimazole and is rarely used today.
Transdermal methimazole (in PLO gel; 2.5 mg twice daily) has been
used with some therapeutic success in cats that do not tolerate oral
dosing. Efficacy may require four or more weeks to detect. Studies
are ongoing.
Methimazole appears to be useful for the prophylactic prevention
of cisplatin induced nephrotoxicity in dogs.
Purification Methods
Crystallise it from EtOH. UV: at 251nm (H2O), 260nm (EtOH) and 267nm (CHCl3). [Lawson max & Morley J Chem Soc 1103 1956, Beilstein 24 H 17, 24 III/IV 61.]
