Affiliation:
1. Chelsea Department of Pharmacy, King’s College London, University of London, UK
Abstract
Abstract
Metabolic TV-oxidation of adenine, 9-methyladenine, 9-benzyladenine, 9-benzhydryladenine and 9-trityladenine has been investigated using hepatic microsomes from hamster, guinea-pig, rabbit, mouse, rat, and dog. N1-Oxide formation occurs with 9-benzyladenine and 9-benzhydryladenine using liver preparations of all species examined, although to different extents. The N-oxidase activity was found, amongst rodents, in the order hamster > mouse > rabbit > rat > guinea-pig. Microsomal preparations from dog liver contained a small quantity of P-450 and yet produced a relatively large amount of the N-oxides, possibly indicating that other cytochromes in addition to P-450 may be involved in the TV-oxidation of these compounds. The most favourable conformations of these 9-substituted analogues have been established using computer graphics modelling and 1H NMR techniques. Results obtained confirmed the importance of the stereochemical properties of these compounds in relation to N1-oxidation. These observations substantiate and extend our previous findings on the electronic, lipophilic, and stereochemical factors affecting the TV-oxidation of adenine derivatives.
Publisher
Oxford University Press (OUP)
Subject
Pharmaceutical Science,Pharmacology
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