Stereoselectivity in S- and N-oxygenation by the mammalian flavin-containing and cytochrome P-450 monooxygenases.
In general, the use of stereoselectivity studies in examining the contribution of monooxygenases or other catalysts to the N- and S-oxidation of drugs, xenobiotics and endogenous substrates provides a useful method to distinguish enzymatic from nonenzymatic processes. Recent developments in this active area of research have been rapid, presumably due to advances in bioanalytical chemistry, chiral stationary-phase HPLC, and attendant breakthroughs in the instruments to measure centers of chirality. This research area has also been aided by the availability of enzymes and other catalysts. In light of the ever-increasing necessity for new single-isomer drugs, metabolites, and other chiral drug market materials, the demand for stereoselectivity information in the drug development business should continue to expand. In the future, demand for enantiomeric intermediates and metabolites to be studied in their own right for pharmacological activity will undoubtedly increase. Finally, technologies related to the creation or characterization of enantiomerically pure drugs or their metabolites presumably will grow because of the increased number of compounds entering the drug development pipeline due to combinatorial chemistry.
Cashman
J R
JR
Human BioMolecular Research Institute, San Diego, California 92121, USA.
D000588:Amines / Q000378:metabolism; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D005415:Flavins / Q000494:pharmacology*; D006801:Humans; D008968:Molecular Conformation; D010100:Oxygen / Q000378:metabolism*; D010105:Oxygenases / Q000737:chemistry / Q000494:pharmacology*; D013440:Sulfides / Q000378:metabolism
D000588:Amines; D005415:Flavins; D013440:Sulfides; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D010100:Oxygen