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98 5 Multi-Enzyme Systems and Cascade Reactions Involving Cytochrome P450 Monooxygenases

Cl Cl Cl
Cl N Cl N Cl N
CYPs CYPs
O 3A4/2C8/2C9 O 3A4/2C8/2C19 O
N N N
S S S
O NH 2 O NH 2 O NH 2
N N N
19
OH HO
20
C20-Hydroxylated metabolite Capravirine C19-Hydroxylated metabolite
CYP 3A4 ( >90% contribution)
CYP 2C8 (<10% contribution)
−
O
Cl Cl
+
Cl N Cl N 26
O O
23 N N
S S
O O NH 2 O NH 2
N N
23-Sulfoxide 26-N-oxide
CYP 3A4 CYP 3A4

Further metabolites Further metabolites
Scheme 5.9 Multistep oxidations in capravirine metabolism. Bold arrows indicate the routes toward the major metabolites,
while dashed arrows show reactions toward minor metabolites.