The structure of the glucuronide of sulphadimethoxine formed in man

Abstract

1. The major metabolite of 2,4-dimethoxy-6-sulphanilamidopyrimidine (sulphadimethoxine) in urine in man is a non-reducing glucuronide, which has been isolated and characterized as its S-benzylthiouronium salt. 2. The same compound was made synthetically by standard methods from sodium sulphadimethoxine and methyl 2,3,4-tri-O-acetyl-1-bromoglucuronate. 3. On hydrolysis with acid, the glucuronide yielded sulphanilic acid, glucuronic acid and barbituric acid, and with beta-glucuronidase it slowly yielded sulphadimethoxine and glucuronic acid. 4. Evidence based on infrared spectra and other data showed that the urinary and synthetic glucuronide was 1-deoxy-1-[N(1)'-(2'',4''-dimethoxypyrimidin-6'' -yl)sulphanilamido-beta-d-glucosid]uronic acid or sulphadimethoxine N(1)-glucuronide. 5. N(1)-Methyl- and N(ring)-methyl derivatives of sulphadimethoxine and 4-methoxy-6-sulphanilamidopyrimidine were prepared and their infrared and ultraviolet spectra determined for comparison.

Biliary excretion in foreign compounds. Sulphonamide drugs in the rat

“…Such glucuronides would be highly polar and would have molecular weights of 441, 472 and 487 respectively, if they were monoglucuronides. The glucuronides of sulphapyridine (2-sulphanilamidopyrid-5-yl glucuronide; Scudi & Childress, 1956) and of sulphadimethoxine (sulphadimethoxine Nl-glucuronide; Bridges et al 1965) are known. The formation of these glucuronides probably accounts for the higher biliary excretion of these three drugs compared with the other nine compounds referred to in the preceding paragraph.…”

Comparative Toxicological, Chemotherapeutic and Pharmacokinetic Studies with Sulphormethoxine and other Sulphonamides in Animals and Man

“…A small proportion of sulphormethoxine is excreted in the form of N4-sulphate [9] but a large proportion is excreted as the N4-acetate.…”

The fate of dichlorophen in the rat

“…5553 DC-Alufolien, Kieselgel 60F254) using two solvent systems: A) benzene-acetone-glacial acetic acid (2 : 1 : 1, by vol); B) chloroform-acetone-glacial acetic acid (24: 8 : I, by vol.). After drying, developed plates were examined under u.v, light (254 nm), and sprayed with the naphtharesorcinol reagent of Bridges et al (4), which gives a blue colour with glucuronic acid conjugates. Dichlorophen had RF values of 0.77 and 0.93 in systems A and B respectively.…”

“…No investigations on the metabolism of dichlorophen are reported in the literature, and we have therefore synthesized [l4C] dichlorophen and studied its fate in the rat as a preliminary to studies in healthy and worm-infested human subjects. [14C]-Dichlorophen (2,2'-dihydroxy-5,5'-dichlorodiphenyl [14C]methane) 4-Chlorophenol (2 g) in methanol (10 ml) was added slowly to ice-cold cone. sulphuric acid (15 ml), and the whole then cooled to -50.…”