An Analysis of the Relative Occurrence of N-Demethylation and N-Oxidation in Xenobiotic Metabolism Using Structure-Reactivity Maps

Abstract

The relative occurrence of N−demethylation and N−oxidation in a structurally diverse set of N−methyl tertiary amines was examined using structure-reactivity maps. A structure-reactivity map of the data indicated important structural features useful for predicting the relative occurrence of these reactions. A steric index which describes the degree of steric hinderance at the N−methyl reaction site is defined. A QSAR between the relative occurrence of N−demethylation and N−oxidation of N−methyl tertiary amines and the steric index was developed.

Key Words:

• N−oxidation
• N−demethylation
• structure-reactivity maps
• QSAR
• molecular similarity