Methazolamide CAS 554-57-4

Introduction：Basic information about Methazolamide CAS 554-57-4, including its chemical name, molecular formula, synonyms, physicochemical properties, and safety information, etc.

Methazolamide Basic information

• Product Name: Methazolamide
• Synonyms: 2-acetylimino-3-methyl-delta(sup4)-1,3,4-thiadiazoline-5-sulfonamide;2-Acetylimino-3-methyl-delta⁴-1,3,4-thiadiazoline-5-sulfonamide;5-acetylimino-4-methyl-delta(sup2)-1,3,4-thiadiazoline-2-sulfonamide;CL 8490;N-[5-(Aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]acetamide;N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)acetamide;N-(3-methyl-5-sulfamoyl-1,3,4-thiadiazol-2-ylidene)ethanamide;Methazolamide (500 mg)
• CAS: 554-57-4
• MF: C5H8N4O3S2
• MW: 236.27
• EINECS: 209-066-7
• Product Categories: VANDID;Other APIs;Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;APIs
• Mol File: 554-57-4.mol

Methazolamide Chemical Properties

• Melting point: 208 °C (dec.) (lit.)
• Boiling point: 402.0±28.0 °C(Predicted)
• density: 1.6625 (rough estimate)
• refractive index: 1.6270 (estimate)
• storage temp.: 2-8°C
• solubility: DMSO: soluble20mg/mL, clear
• pka: 7.30(at 25℃)
• form: White powder
• color: white to beige
• Water Solubility: 2.835g/L(25 ºC)
• InChI: InChI=1S/C5H8N4O3S2/c1-3(10)7-4-9(2)8-5(13-4)14(6,11)12/h1-2H3,(H2,6,11,12)
• InChIKey: FLOSMHQXBMRNHR-QPJJXVBHSA-N
• SMILES: C(N=C1N(C)N=C(S(N)(=O)=O)S1)(=O)C
• CAS DataBase Reference: 554-57-4(CAS DataBase Reference)
• NIST Chemistry Reference: Methazolamide(554-57-4)
• EPA Substance Registry System: Acetamide, N-[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]- (554-57-4)

Safety Information

• Hazard Codes: Xn
• Risk Statements: 20/21/22-40
• Safety Statements: 22-36
• WGK Germany: 3
• RTECS: AC6350000
• HS Code: 2935904000
• Storage Class: 11 - Combustible Solids
• Hazard Classifications: Acute Tox. 4 Dermal Acute Tox. 4 Inhalation Acute Tox. 4 Oral Carc. 2
• Hazardous Substances Data: 554-57-4(Hazardous Substances Data)

Methazolamide Usage And Synthesis

Description

Methazolamide is a carbonic anhydrase inhibitor (IC₅₀ = 130 nM). It reduces intraocular pressure and cerebrospinal fluid flow in a rat model of glaucoma. Methazolamide reduces electroshock-induced seizures in rats with an ED₅₀ value of 19.2 mg/kg. It also inhibits production of reactive oxygen species (ROS) in a primary cortical neuron (PCN) cellular model of subarachnoid hemorrhage (SAH) and reduces cerebral edema in a mouse model of SAH. Methazolamide is larvicidal, with a larvicidal concentration (LC₅₀) value of 724 ppm, but has no activity when administered in the diet to adult A. aegypti. Formulations containing methazolamide have been used for the treatment of glaucoma.

Chemical Properties

White Solid

Originator

Neptazane ,Lederle,US,1959

Uses

Methazolamide is a carbonic anhydrase inhibitor. Methazolamide is used in the treatment of glaucoma.

Uses

CNS & respiratory stimulant

Uses

Action of this drug is similar to that of acetazolamide, and it is used for lowering intraocularpressure in treating wide-angle and secondary glaucoma, and before surgical interventionfor severe wide-angle glaucoma.

Definition

ChEBI: Methazolamide is a member of thiadiazoles and a sulfonamide.

Manufacturing Process

A suspension of 6 parts by weight of 5-acetylimino-4-methyl-2- benzylmercapto-δ2-1,3,4-thiadiazoline in 180 parts by volume of 33% aqueous acetic acid was chlorinated at 5°C for 30 minutes. The solid was filtered off, dried, and added portion-wise to 100 parts by volume of liquid ammonia. The ammonia was removed under a stream of dry nitrogen.
The residual solid was partially dissolved in 10 parts by volume of water, filtered, and acidified to give 5-acetylimino-4-methyl-δ2-1,3,4-thiadiazoline-2- sulfonamide. The product was purified by two recrystallizations from hot water.

Therapeutic Function

Carbonic anhydrase inhibitor

Biochem/physiol Actions

Methazolamide is a cell-permeable and potent carbonic anhydrase (CA) inhibitor that is used in the treatment of glaucoma. Methazolamide is an insulin sensitizer that reduces hepatic glucose generation in animal models.

Clinical Use

Methazolamide is a derivative of acetazolamide in which one of the active hydrogens has been replaced by a methyl group. This decreases the polarity and permits agreater penetration into the ocular fluid, where it acts as a carbonic anhydrase inhibitor, reducing intraocular pressure. Its dose for glaucoma is 50 to 100 mg two to threetimes a day.

Synthesis

Methazolamide, N-(4-methyl-2-sulfamoyl-1,3,4-thiadiazol-5-yliden)acetamide (21.2.3), is made by an intermediate product of acetazolamide synthesis?a2-acetylamino-5-mercapto-1,3,4-thadiazol (9.7.3). This is benzylated with benzylchloride atthe mercapto group, forming 2-acetylamino-5-benzylthio-1,3,4-thiadiazole (21.2.1). Furthermethylation of the product with methyl iodide leads to the formation of N-(4-methyl-2-benzylthio-1,3,4-thiadiazol-5-yliden)acetamide (21.2.2). Oxidation and simultaneouschlorination of the resulting product with chlorine in an aqueous solution of acetic acid, andreacting the resulting chlorosulfonic derivative with ammonia gives (21.2.3).

Veterinary Drugs and Treatments

Orally administered methazolamide is used for the medical treatmentof glaucoma.

References

[1] MAREN T H. Carbonic anhydrase: chemistry, physiology, and inhibition.[J]. Physiological reviews, 1967, 47 4: 595-781. DOI: 10.1152/physrev.1967.47.4.595
[2] WILLIAM D. GRAY  Charles E R. The anticonvulsant action of the carbonic anhydrase inhibitor methazolamide: Possible involvement of a noradrenergic mechanism[J]. European journal of pharmacology, 1974, 28 1: Pages 42-54. DOI: 10.1016/0014-2999(74)90110-1
[3] MINGCHANG LI. Methazolamide improves neurological behavior by inhibition of neuron apoptosis in subarachnoid hemorrhage mice[J]. Scientific Reports, 2016, 6 1. DOI: 10.1038/srep35055

Methazolamide Preparation Products And Raw materials

• Raw materials: Ammonia-->Chlorine