In vitrobiotransformation of thiazopyr by rat liver microsomes: Oxidative cleavage of a carboxylic methylester by monooxygenases

Abstract

1. Thiazopyr was metabolized by liver microsomes from male Sprague-Dawley rats to a previously unidentified metabolite. 2. The new metabolite was identified by coelution with an authentic standard in hplc and by electrospray lc/ms as the corresponding carboxylic acid. 3. Formation of the carboxylic acid metabolite was inhibited in the presence of mono-oxygenase inhibitors including piperonyl butoxide, 1-aminobenzotriazole, metyrapone and tetcyclacis. 4. Transformation of thiazopyr to its carboxylic acid by rat liver microsomes is mediated by mono-oxygenases and not hydrolases.

1-Aminobenzotriazole: A Mechanism-Based Cytochrome P450 Inhibitor and Probe of Cytochrome P450 Biology

“…The conversion by rat liver microsomes of the esterified pesticide thiazopyr to the free acid is inhibited by 1-ABT and is thus mediated by a cytochrome P450 enzyme rather than by an esterase ( Figure 8 ) [ 116 ]. Using 1-ABT, cytochrome P450 catalysis in the endoplasmic reticulum was found in another instance to contribute to the instability of a TGR5 receptor agonist with a central amide bond [ 117 ].…”

An Efficient Route to Difluoromethylated Pyridines

“…5 Several difluoromethylated pyridines, such as dithiopyr and thiazopyr, show herbicidal activities. [6][7][8][9] The development of efficient methodologies for the synthesis of difluoromethyl pyridines is therefore of considerable importance. 10,11 One of the most useful methods for constructing difluoromethylated pyridines is by the direct introduction of a difluoromethyl group onto a pyridine skeleton.…”