6-Ethoxy-2-benzothiazolesulfonamide

Originator

Cardrase,Upjohn,US,1957

Uses

Ethoxzolamide is used in the treatment of glaucoma, and is also used as a diuretic, acting as a carbonic anhydrase inhibitor.

Uses

alcohol dehydrogenase inhibitor, antidote

Definition

ChEBI: 1,3-Benzothiazole substituted a sulfonamide and an ethoxy group at positions 2 and 6, respectively. A carbonic anhydrase inhibitor, it has been used in the treatment of glaucoma, and as a diuretic.

Manufacturing Process

Preparation of 6-Ethoxybenzothiazole-2-Sulfenamide: A solution prepared by dissolving 21.0 grams (0.1 mol) of 6-ethoxybenzothiazole-2-thiol, Sebrell and Boord, J. Am. Chem. Soc. 45: 2390 to 2399 (1923), in 75 ml of water containing 5 grams of sodium hydroxide, and 75 ml of 10% sodium hypochlorite solution were added simultaneously to 300 ml of concentrated ammonium hydroxide which was cooled to 0°C, and vigorously stirred. During the addition the temperature was not allowed to rise above 5°C. The resulting solid was recovered by filtration, washed thoroughly with water, and dried at room temperature under reduced pressure. There was obtained 21 grams of 6-ethoxybenzothiazole-2-sulfenamide melting at 132° to 155°C (decomposition). Recrystallization from ethyl acetate gave a product melting at 140.5° to 143°C (decomposition).
Preparation of 6-Ethoxybenzothiazole-2-Sulfonamide: A solution of 3.39 grams (0.015 mol) of the sulfenamide in 100 ml of acetone was treated dropwise, with stirring, with a solution of 3.5 grams of potassium permanganate in 100 ml of water. The temperature rose to 42°C. After stirring an additional 10 minutes the reaction mixture was filtered to remove manganese dioxide, the latter was washed with 100 ml of warm water, and the combined filtrates were concentrated under reduced pressure to remove acetone. The residual solution was treated with charcoal, filtered and acidified with concentrated hydrochloric acid. After standing in the refrigerator for 4 hours the solid sulfonamide was recovered by filtration, washed with water and dried. There was obtained 2.37 grams of 6-ethoxybenzothiazole-2-sulfonamide melting at 180° to 190°C. Recrystallization from ethyl acetate-Skellysolve B gave 1.25 grams of material melting at 188° to 190.5°C.

Therapeutic Function

Diuretic, Cardiotonic, Smooth muscle relaxant, Respiratory stimulant

General Description

6-Ethoxy-2-benzothiazolesulfonamide is a membrane permeable carbonic anhydrase inhibitor and its ocular disposition and pharmacology in normal albino rabbits has been investigated. It causes inhibition of insulin degradation in vitro.

Clinical Use

Ethoxzolamide is another carbonic anhydrase inhibitor with properties and uses resembling those of acetazolamide.