Metabolism of derivatives of toluene. 2. Nuclear methyl-substituted derivatives of N-phenylurea

Abstract

The metabolism of the 3 N-tolylureas in the rabbit was shown to be similar to that of the corresponding acetotoluidides. The ureido group in these compounds appeared to be stable in the rabbit and to rabbit-liver extract in vitro. o-Tolylurea was converted to N-(4-hy-droxy-2-methylphenyl)-urea (35% of the dose) which was excreted as ethereal sulfate (4%) and glucuronide (31%). The methyl group was not oxidized to any appreciable extent. Some o-tolylurea was excreted unchanged. m-Tolylurea was oxidized to m-ureidobenzoic acid (45%), 4% of which was excreted as ester glucuronide, and hydroxylated to N-(4-hydroxy-3-methyl-phenyl)-urea (24%), of which 10% was excreted as ethereal sulfate and 14% as ether glucuronide. Some m-tolylurea was excreted unchanged. p-Tolylurea was almost completely oxidized to p-ureidobenzoic acid (86%), of which only 6% was conjugated as ester glucuronide, the remainder was excreted free. N-phenylurea was partly hydroxylated to N-(p-hydroxy-phenyl)-urea (46%) which was conjugated almost equally with sulfuric acid (20%) and glucuronic acid (26%). Some N-phenylurea was excreted unchanged. 4- Ureidophenylglucuronide was isolated from N-phenylurea urine as its crystalline K salt.