Identification of urinary metabolites of ecabapide in rat

Abstract

1. 14C-Ecabapide, 3-[[[2-(3,4-dimethoxyphenyl)ethyl]carbamoyl]methyl]amino-N- methyl[14C]benzamide, was dosed orally to rat (100 mg/kg). Within 48h after dosing, 36.7 +/- 5.4 and 55.7 +/- 11.8% of the administered radioactivity was recovered from urine and faeces respectively. 2. The unchanged drug was the major compound excreted in the urine and accounted for 37% of the urinary radioactivity. Seven urinary metabolites were purified by preparative hplc and their structures were elucidated by mass and 1H-nmr spectrometry. 3. The major metabolic pathway of ecabapide was found to be the formation of 3-amino-N-methylbenzamide produced by N-dealkylation of the secondary amine at the 3-position of the benzamide moiety followed by acetylation. 4. Further metabolic pathways of the N-methylbenzamide moiety were N-demethylation via the carbinolamine derivatives, and/or aromatic hydroxylation followed by glucuronidation.

Aminosalicylic acid conjugates of EDTA as potential anti-inflammatory pro-drugs: synthesis, copper chelation and superoxide dismutase-like activities

“…The methyl esters of 4-ASA and 5-ASA were synthesised using a modified method of that previously described by Fajimaki et al [35]. The methyl esters were then conjugated to the dianhydride of EDTA, EDTAD, using standard amide preparation techniques (Fig.…”

In Vitro Metabolism of 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin in Human Liver Microsomes

“…Furthermore, a stable carbinolamine, hydroxymethylpentamethylmelamine, was detected as a metabolite in mouse plasma (Abikhalil et al, 1986) and rat liver microsomes (Ames et al, 1983) because the adjacent substituents delocalize the lone pair nitrogen electrons and stabilize the carbinolamine. In addition, stable carbinolamines have been isolated or detected as metabolites to a number of drugs including benzamides (Huizing et al, 1980), carbamates (Dorough and Casida, 1964), procarbazine (Weinkam and Shiba, 1978), N-methylcarbazole (Ebner et al, 1991), medazepam (Schwartz and Kolis, 1972), verapamil (Walles et al, 2002), pyrimidinyl-pyridopyrazines (Prakash and Soliman, 1997), and ecabapide (Fujimaki et al, 1995). Quinone is known as an electron-withdrawing group by resonance (Hiramatsu et al, 1983).…”