| Chemical Properties | Off-White Solid |
| Originator | Daranide,MSD ,US,1958 |
| Uses | Like the drugs described above, dichlorphenamide is used for secreting excess water incases of elevated intraocular pressure, and it is used for treating wide-angle and secondaryglaucoma as well as in cases where it is necessary to lower intraocular pressure before surgicalintervention in severe wide-angle glaucoma. |
| Uses | Diclofenamide is a potent carbonic anhydrase inhibitor. Diclofenamide may provide a therapeutic strategy in the inhibition of the human cytosolic isoforms I and II and transmembrane tumor-associated isoenzymes IX and XII. Diclofenamide has been shown to be is effective in the prevention of episodic weakness in both hypokalemic periodic paralysis (HypoPP) and potassium-sensitive periodic paralysis (PSPP). |
| Definition | ChEBI: A sulfonamide that is benzene-1,3-disulfonamide in which the hydrogens at positions 4 and 5 are substituted by chlorine. An oral carbonic anhydrase inhibitor, it partially suppresses the secretion (inflow) of aqueous humor in the eye and so reduces intraoclar pressure. It is used for the treatment of glaucoma. |
| Manufacturing Process | In a 2 liter round-bottomed flask equipped with stirrer and dropping funnel isplaced 1,585 grams (880 cc; 13.6 mols) of chlorosulfonic acid. To this isadded dropwise with stirring during 5 hours 218 grams (1.7 mols) of ochlorophenol. The mixture is allowed to stand 1 hour at room temperatureand then is heated 1 hour on a steam bath. The mixture is then poured onice.
A product consisting largely of 5-chloro-4-hydroxybenzene-1,3-disulfonylchloride separates as a gum which solidifies on standing for about 1 hour. Thesolid product is collected on a Buchner funnel, washed with water andthoroughly dried in air at room temperature.
A mixture of this crude product (approximately 302 grams, 0.92 mol) and 480grams (2.3 mols) of phosphorus pentachloride is heated for 1 hour at 120°-140°C in a 2 liter round-bottomed flask. The resulting clear solution is pouredon ice. 4,5-Dichlorobenzene-1,3-disulfonyl chloride separates immediately as asolid. It is collected by filtration and washed with water. While still moist, it isadded in portions during about 20 minutes to 1 liter of concentrated ammoniawater contained in a 3 liter beaker surrounded by a cold water bath. Thereaction mixture is then allowed to stand for 1 hour without cooling afterwhich it is heated on a steam bath for about 30 minutes while air is bubbledthrough it, in order to remove some of the excess ammonia. It is thenfiltered, acidified with concentrated hydrochloric acid and chilled.
The product separates as a gum from which the supernatant liquid isdecanted, and the gum is triturated with 250 cc of water in order to inducecrystallization. The crude product thus obtained is recrystallized from 3,200 cc of boiling water and then from 40% aqueous isopropyl alcohol yielding 4,5-dichlorobenzene-1,3-disulfonamide as a white solid, MP 228.5° to 229.0°C. of boiling water and then from 40% aqueous isopropyl alcohol yielding 4,5-dichlorobenzene-1,3-disulfonamide as a white solid, MP 228.5° to 229.0°C. |
| Brand name | Daranide (Merck). |
| Therapeutic Function | Carbonic anhydrase inhibitor, Antiglaucoma |
| Clinical Use | Dichlorphenamide is a disulfonamide derivative thatshares the same pharmacological properties。The dose of dichlorphenamide is 25 to 100 mg one to three timesa day. |
| Synthesis | Dichlorphenamide, 4,5-dichlorbenzol-1,3-disulfonamide (21.2.6), ismade in a relatively simple way from 2-chlorophenol. 2-Chlorophenol undergoes sulfochlorinationby chlorosulfonic acid, forming 4-hydroxy-5-chlorobenzol-1,3-disulfonylchloride (21.2.4). The hydroxyl group is replaced by a chlorine atom using phosphorouspentachloride, giving 4,5-dichlorobenzol-1,3-disulfonylchoride (21.2.5), the reactionof which with ammonia gives the desired dichlorphenamide (21.2.6). |
| Veterinary Drugs and Treatments | Dichlorphenamide is used for the medical treatment of glaucoma.Because of availability issues and toxic effects associated with systemictherapy, human (and many veterinary) ophthalmologists areusing topical carbonic anhydrase inhibitors (e.g., dorzolamide orbrinzolamide) in place of acetazolamide, dichlorphenamide or methazolamide. |
