Application of chemical P-450 model systems to study drug metabolism. III. Metabolism of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine.
Oxidation of 3-isobutyryl-2-isopropylpyrazolo[1,5-alpha]pyridine (IBPP) was carried out with various chemical model systems for cytochrome P-450 in comparison with the liver microsomal system of rats or humans. Alpha-hydroxylation of side chains and ring hydroxylation at the 6 and 7 positions were the main reactions in both systems. A pattern analysis of products using two dimensional thin layer chromatography was employed to compare the functions of the chemical model systems with those of microsomal systems. The reaction profile of IBPP by the catalyst/Pt-colloid/H2, O2 system was most similar to that of human or rat microsomal system. The utility of these chemical models is discussed from the viewpoint of drug metabolism.
Nagatsu
Y
Y
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Higuchi
T
T
Hirobe
M
M
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D007212:Indolizines; D011720:Pyrazoles
D003577:Cytochrome P-450 Enzyme System; D011725:Pyridines; C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles