Sulphones

Antileprotic Drugs - SYNTHESIS AND DRUG PROFILE

Sulphones

i. Dapsone (DDS, Diaminodiphenyl sulphone)

Synthesis

Route I. From: 4-chloro nitrobenzene

Route II. From: 4-Chloro nitrobenzene

Metabolism: The major metabolic product of Dapsone results from N-acetylation in the liver by N-acetyltransferase. It also undergoes N-hydroxylation to hydroxylamine derivative. These metabolic reactions are catalyzed by CYP3A4 isoforms. Neither of these compounds possesses significant leprostatic activity, although N-acetyldiamino-diphenyl sulphone may be deacetylated back to Dapsone. Products found in the urine consist of small amounts of Dapsone and the metabolites, that is, N-acetyldiamino-diphenyl sulphone and N-hydroxy-diamino-diphenyl sulfone, as well as glucuronide and sulphate of each of these substances.

Properties and uses: Dapsone is a white or slightly yellowish-white crystalline powder, very slightly soluble in water, soluble in acetone and dilute mineral acids, but sparingly soluble in alcohol. It is a folic acid synthesis inhibitor used in both lepromatous and tuberculoid leprosy.

Assay: Dissolve the sample in dilute hydrochloric acid and add potassium bromide. Cool in ice and titrate against 0.1 N sodium nitrate. Determine the end point electrometrically.

Dosage: The dose as tablets is 25 or 100 mg. For adults the dose consumed is 50 mg per day orally. For lepromatous leprosy, 100 mg Dapsone + 600 mg Rifampin and/or clofazimine 100 mg daily for at least 2 years followed by Dapsone monotherapy. For borderline tuberculoid disease, Dapsone 100 mg daily + Rifampin 600 mg once monthly for 6 months.

Dose : Dapsone tablets I.P., B.P.

ii. Solapsone Sodium

Synthesis

Acedapsone

Synthesis

Route I: From Dapsone

Route II: From 4-Chloro nitrobenzene

Properties and uses: Acedapsone (prodrug of Dapsone) is used in the treatment of both lepromatous and tuberculoid type of leprosy.