PT - JOURNAL ARTICLE AU - Hye Hyun Yoo AU - Hye Jin Chung AU - Jaeick Lee AU - Chang-Seok Lee AU - Min Jung Kang AU - Dong-Hyun Kim TI - Enzymatic <em>C</em>-Demethylation of 1-[2-(5-<em>tert</em>-Butyl-[1,3,4] oxadiazole-2-carbonyl)-4-fluoro-pyrrolidin-1-yl]-2-(2-hydroxy-1,1-dimethyl-ethylamino)-ethanone (LC15-0133) in Rat Liver Microsomes AID - 10.1124/dmd.107.019133 DP - 2008 Mar 01 TA - Drug Metabolism and Disposition PG - 485--489 VI - 36 IP - 3 4099 - http://dmd.aspetjournals.org/content/36/3/485.short 4100 - http://dmd.aspetjournals.org/content/36/3/485.full SO - Drug Metab Dispos2008 Mar 01; 36 AB - The in vitro metabolism of 1-[2-(5-tert-butyl-[1,3,4] oxadiazole-2-carbonyl)-4-fluoro-pyrrolidin-1-yl]-2-(2-hydroxy-1,1-dimethyl-ethylamino)-ethanone (LC15-0133), a novel dipeptidyl peptidase-4 inhibitor, was investigated using a hepatic microsomal system. The structures of the metabolites were characterized using mass spectral analysis and by comparison with synthetic references. The in vitro incubation of LC15-0133 with rat liver microsomes resulted in the formation of six metabolites, with the major metabolic reactions being hydroxylation and carbonyl reduction. Of the metabolites, a C-demethylated metabolite (M4) was identified, but was only detected in rat liver microsomes; experimental evidence revealed that the C-demethylated metabolite was generated by nonenzymatic decarboxylation of the carboxyl metabolite (M1). Nonenzymatic decarboxylation is postulated to occur due to the resonance stabilization by the oxadiazole ring attached to the tert-butyl moiety. The American Society for Pharmacology and Experimental Therapeutics