are found to undergo this reaction to a marked extent in humans, as exemplified by the N + -glucuronide of imipramine (48, Figure 16). The same is true for pyridine-type tertiary amines, as exemplified by two important conjugates of nicotine in humans, namely the N + -glucuronide of nicotine (49; X = 2 H) and cotinine (49; X = O).
UGT1A4 plays a particularly important role in N-glucuronidation, but there are extensive overlaps in the specificity of the various UGTenzymes toward the various classes of substrates discussed above (Table 3). QSAR, 3D-QSAR, and pharmacophore modeling are beginning to clarify these specificities and offer preliminary predictive models.46'90'91
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