554-57-4

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;5-Acetylimino-4-methyl-delta2-1,3,4-thiadiazoline-2-sulfonamide;Acetamide, N-(4-methyl-2-sulfamoyl-delta2-1,3,4-thiadiazolin-5-ylidene)-;Acetamide, N-[5-(aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene]-;Methenamide;N-((2Z)-5-(Aminosulfonyl)-3-methyl-1,3,4-thiadiazol-2(3H)-ylidene)acetamide
• CAS NO: 554-57-4
• Molecular Formula: C₅H₈N₄O₃S₂
• Molecular Weight: 236.27
• EINECS: 209-066-7
• Product Categories: Heterocycles;Inhibitors;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds;VANDID;Other APIs
• Mol File: 554-57-4.mol
• Article Data: 0

Chemical Properties

• Melting Point: 208 °C (dec.)(lit.)
• Boiling Point: 402°Cat760mmHg
• Flash Point: 196.9°C
• Appearance: white to beige/
• Density: 1.6625 (rough estimate)
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.6270 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO: soluble20mg/mL, clear
• PKA: 7.30(at 25℃)
• Water Solubility: 2.835g/L(25 oC)
• CAS DataBase Reference: Methazolamide(CAS DataBase Reference)
• NIST Chemistry Reference: Methazolamide(554-57-4)
• EPA Substance Registry System: Methazolamide(554-57-4)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-40
• Safety Statements: 22-36
• WGK Germany: 3
• RTECS: AC6350000
• Hazardous Substances Data: 554-57-4(Hazardous Substances Data)

Usage

Description

Methazolamide is a carbonic anhydrase inhibitor with a wide range of applications in the medical field. It is known for its ability to reduce intraocular pressure and cerebrospinal fluid flow, making it a valuable treatment for glaucoma. Additionally, Methazolamide has demonstrated neuroprotective properties, as it reduces electroshock-induced seizures and inhibits the production of reactive oxygen species in a cellular model of subarachnoid hemorrhage. Furthermore, Methazolamide has shown larvicidal activity, although it does not have an effect when administered to adult A. aegypti.
Used in Ophthalmology:
Methazolamide is used as a carbonic anhydrase inhibitor for the treatment of glaucoma. It helps to reduce intraocular pressure, which is crucial in managing this eye condition and preventing further damage to the optic nerve.
Used in Neuroprotection:
Methazolamide is used as a CNS and respiratory stimulant, similar to acetazolamide. It is effective in lowering intraocular pressure and treating wide-angle and secondary glaucoma. Additionally, it is used before surgical intervention for severe wide-angle glaucoma, providing a valuable pre-treatment option for patients.
Used in Neurological Disorders:
Methazolamide is used as a neuroprotective agent in a primary cortical neuron cellular model of subarachnoid hemorrhage. It reduces cerebral edema and inhibits the production of reactive oxygen species, which can contribute to neuronal damage.
Used in Insect Control:
Methazolamide is used as a larvicide, with a larvicidal concentration (LC50) value of 724 ppm. This property makes it a potential candidate for controlling the larval stages of certain insect species, although it has no activity when administered in the diet to adult A. aegypti.

Originator

Neptazane ,Lederle,US,1959

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.

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 a greater 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 three times 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— 2-acetylamino-5-mercapto-1,3,4-thadiazol (9.7.3). This is benzylated with benzylchloride at the mercapto group, forming 2-acetylamino-5-benzylthio-1,3,4-thiadiazole (21.2.1). Further methylation 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 simultaneous chlorination of the resulting product with chlorine in an aqueous solution of acetic acid, and reacting the resulting chlorosulfonic derivative with ammonia gives (21.2.3).

Veterinary Drugs and Treatments

Orally administered methazolamide is used for the medical treatment of glaucoma.

InChI:InChI=1/C5H8N4O3S2/c1-3(10)7-4-9(2)8-5(13-4)14(6,11)12/h1-2H3,(H2,6,11,12)/b7-4+

Synthetic route

L-Cysteine (52-90-4) + methazolamide (554-57-4) → S-(5-acetylimino-4-methyl-Δ2-1,3,4-thiazolidin-2-yl)cysteine

Conditions	Yield
With ammonium formate In water at 20℃; pH=.8;	57%

Upstream product

• 114224-34-9 5-acetylimino-4-methyl-4,5-dihydro-[1,3,4]thiadiazole-2-sulfonyl chloride