120-97-8 Usage
Description
Diclofenamide, also known as Daranide, is a potent carbonic anhydrase inhibitor and a sulfonamide derivative. It is an off-white solid that acts as an oral carbonic anhydrase inhibitor, partially suppressing the secretion of aqueous humor in the eye, thereby reducing intraocular pressure. It is primarily used for the treatment of glaucoma.
Uses
Used in Ophthalmology:
Diclofenamide is used as a therapeutic agent for treating wide-angle and secondary glaucoma. It helps in lowering intraocular pressure, which is essential in managing these conditions and preventing further damage to the eye.
Used in Neuromuscular Disorders:
Diclofenamide serves as a preventive measure for episodic weakness in hypokalemic periodic paralysis (HypoPP) and potassium-sensitive periodic paralysis (PSPP). Its carbonic anhydrase inhibitory properties contribute to the management of these conditions.
Used in Oncology:
Diclofenamide may provide a therapeutic strategy in the inhibition of human cytosolic isoforms I and II and transmembrane tumor-associated isoenzymes IX and XII. This makes it a potential candidate for cancer treatment, although further research is needed to explore its full potential in this area.
Used in Pre-surgical Interventions:
In cases of severe wide-angle glaucoma, diclofenamide is used to lower intraocular pressure before surgical intervention. This helps in reducing the risk of complications and improving the outcomes of the surgery.
Originator
Daranide,MSD ,US,1958
Manufacturing Process
In a 2 liter round-bottomed flask equipped with stirrer and dropping funnel is
placed 1,585 grams (880 cc; 13.6 mols) of chlorosulfonic acid. To this is
added dropwise with stirring during 5 hours 218 grams (1.7 mols) of ochlorophenol. The mixture is allowed to stand 1 hour at room temperature
and then is heated 1 hour on a steam bath. The mixture is then poured on
ice.A product consisting largely of 5-chloro-4-hydroxybenzene-1,3-disulfonyl
chloride separates as a gum which solidifies on standing for about 1 hour. The
solid product is collected on a Buchner funnel, washed with water and
thoroughly dried in air at room temperature.A mixture of this crude product (approximately 302 grams, 0.92 mol) and 480
grams (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 poured
on ice. 4,5-Dichlorobenzene-1,3-disulfonyl chloride separates immediately as a
solid. It is collected by filtration and washed with water. While still moist, it is
added in portions during about 20 minutes to 1 liter of concentrated ammonia
water contained in a 3 liter beaker surrounded by a cold water bath. The
reaction mixture is then allowed to stand for 1 hour without cooling after
which it is heated on a steam bath for about 30 minutes while air is bubbled
through it, in order to remove some of the excess ammonia. It is then
filtered, acidified with concentrated hydrochloric acid and chilled.The product separates as a gum from which the supernatant liquid is
decanted, and the gum is triturated with 250 cc of water in order to induce
crystallization. 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.
Therapeutic Function
Carbonic anhydrase inhibitor, Antiglaucoma
Clinical Use
Dichlorphenamide is a disulfonamide derivative that
shares the same pharmacological properties。The dose of dichlorphenamide is 25 to 100 mg one to three times
a day.
Synthesis
Dichlorphenamide, 4,5-dichlorbenzol-1,3-disulfonamide (21.2.6), is
made in a relatively simple way from 2-chlorophenol. 2-Chlorophenol undergoes sulfochlorination
by chlorosulfonic acid, forming 4-hydroxy-5-chlorobenzol-1,3-
disulfonylchloride (21.2.4). The hydroxyl group is replaced by a chlorine atom using phosphorous
pentachloride, giving 4,5-dichlorobenzol-1,3-disulfonylchoride (21.2.5), the reaction
of 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 systemic
therapy, human (and many veterinary) ophthalmologists are
using topical carbonic anhydrase inhibitors (e.g., dorzolamide or
brinzolamide) in place of acetazolamide, dichlorphenamide or methazolamide.
Check Digit Verification of cas no
The CAS Registry Mumber 120-97-8 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 1,2 and 0 respectively; the second part has 2 digits, 9 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 120-97:
(5*1)+(4*2)+(3*0)+(2*9)+(1*7)=38
38 % 10 = 8
So 120-97-8 is a valid CAS Registry Number.
InChI:InChI=1/C7H5Cl2NO/c8-5-3-1-2-4(6(5)9)7(10)11/h1-3H,(H2,10,11)
120-97-8Relevant articles and documents
Identification, isolation and origin of potential dimer impurities of dichlorphenamide: A carbonic anhydrase inhibitor drug (antiglaucoma)
REDDY, T. PURENDAR,DUSSA, NAGESHWAR,MAMIDI, SRINIVAS,PANASA, MAHESH,CHAVAKULA, RAMADAS,PADMA
, p. 1249 - 1252 (2021/06/09)
Present work describes the identification, isolation and characterization of two new process related dimeric impurities of dichlorphenamide (1). During the synthesis of dichlorphenamide, the formation of two new dimeric impurities namely 2,3-dichloro-5-(3,4-dichloro-5- sulfamoyl-phenyl)sulfonyl-benzenesulfonamide (2) (1,1'-dichlorphenamide dimer) and 2,3-dichloro-5-(2,3-dichloro-5-sulfamoylphenyl) sulfonyl-benzenesulfonamide (3) (1,3'-dichlorphenamide dimer) was observed. In addition, origin and the strategies adapted to control these potential dimer impurities were also described. These impurities have a substantial impact on the quality of the drug substance as well as drug product.