Lee, J La, S Ahn, BR Jeong, TC Kim, DH 2024-01-21T07:04:21Z 2024-01-21T07:04:21Z 2021-09-02 2004-06 0951-4198 https://pubs.kist.re.kr/handle/201004/137559 The metabolism of a novel anti-cancer agent, 1-{3-[3-(4-cyanobenzyl)-3H-imidazol-4-yl]-propyl}-3-(6-methoxypyridin-3-yl)-1-(2-trifluoromethylbenzyl)thiourea (YH3945), was investigated in rats. Bile, plasma, feces, and urine were collected and analyzed by a high-performance liquid chromatography (HPLC) system equipped with ultraviolet (UV), mass spectrometric, and radioactivity detectors. After intravenous dosing, mean radiocarbon recovery was 74.4+/-1.3% with 62.4+/-1.2% in the feces and 12.0+/-0.5% in the urine. Biliary excretion of the radioactivity for the first 24 It period was approximately 32%, suggesting that YH3945 is cleared by hepatobiliary excretion. YH3945 was extensively metabolized to 21 different metabolites including glucuronide conjugates, and structures of the metabolites were elucidated based on MSn and NMR spectral analyses. The major metabolic pathways in the rat were identified as O-demethylation of methoxypyridine, N-debenzylation of imidazole, and hydroxylation. Cyclic metabolites were also identified; concomitant demethylation in the methoxypyridine moiety and hydroxylation at the C16 position might destroy the chemical stability of the compound and subsequently lead to non-enzymatic cyclization. Cyclic metabolites were characteristic of YH3945, and a non-enzymatic reaction mechanism for the formation of cyclic metabolites was postulated. Copyright (C) 2004 John Wiley Sons, Ltd. English WILEY MASS-SPECTROMETRY RAS Metabolism of 1-{3-[3-(4-cyanobenzyl)-3H-imidazol-4-yl]-propyl}-3-(6-methoxypyridin-3- yl)-1-(2-trifluoromethylb enzyl) thiourea (YH3945), a novel anti-cancer drug, in rats using the C-14-labeled compound Article 10.1002/rcm.1555 1 RAPID COMMUNICATIONS IN MASS SPECTROMETRY, v.18, no.17, pp.1901 - 1910 RAPID COMMUNICATIONS IN MASS SPECTROMETRY 18 17 1901 1910 scie scopus 000223410300005 2-s2.0-4043055079 Biochemical Research Methods Chemistry, Analytical Spectroscopy Biochemistry & Molecular Biology Chemistry Spectroscopy Article MASS-SPECTROMETRY RAS