Bioactivation of a Dihydropyrazole-1-carboxylic acid-(4-chlorophenyl amide) Scaffold to a Putative p-Chlorophenyl Isocyanate in Rat Liver Microsomes and In Vivo in Rats

Compound I (4,5-dihydropyrazole-1,5-dicarboxylic acid-1-[(4-chlorophenyl)-amide] 5-[(2-oxo-2H-[1,3′]bipyridinyl-6′-yl)-amide] was found to undergo metabolic activation in rat liver microsomes in the presence of NADPH. A reactive intermediate, postulated to be p-chlorophenyl isocyanate (CPIC), was tr...

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