1. Chapter 09
Prodrugs and Drug Delivery Systems

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Figure 9.1 (A) Brentuximab vedotin, the first antibody-drug conjugate with a more stable linker; (B) Trastuzumab emtansine, the second antobody-drug conjugate approved
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Scheme 9.1 Protecting group analogy for a prodrug
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Scheme 9.2 Intramolecular catalysis of succinate esters
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Scheme 9.3 Bioreductively activated carrier-linked prodrug
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Scheme 9.4 Liver metabolism of drugs containing phosphate and phosphonate moieties
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Scheme 9.5 Nitrogen mustard activation by carboxypeptidase G2 for use with ADEPT
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Scheme 9.6 Catalytic antibody 38C2 activation of a doxorubicin prodrug by tandem retro-aldol/retro-Michael reactions for use with ADAPT
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Scheme 9.7 Nitroreductase activation of a prodrug for use with GDEPT
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Scheme 9.8 Antibody-targeted chemotherapy, a prodrug for calicheamicin
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Scheme 9.9 Tripartite prodrugs
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Scheme 9.10 Double prodrug concept
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Scheme 9.11 Tripartite prodrugs of ampicillin
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Scheme 9.12 Redox drug delivery system to cross the blood–brain barrier
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Scheme 9.13 Redox tripartite drug delivery system
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Scheme 9.14 Redox tripartite drug delivery of β-lactam antibiotics
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Scheme 9.15 Activation of peptidyl derivatives of 5-fluorouracil
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Scheme 9.16 Tripartite macromolecular drug delivery system
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Scheme 9.17 Mechanism of inactivation of H+,K+-ATPase by omeprazole
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Scheme 9.18 Conversion of leinamycin into a series of prodrugs
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Scheme 9.19 Hydrolytic activation of leinamycin prodrugs
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Scheme 9.20 Activation of leflunomide to the active drug
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Scheme 9.21 Bioprecursor prodrugs for alprazolam and triazolam
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Scheme 9.22 Cytochrome P450-catalyzed activation of cyclophosphamide
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Scheme 9.23 Cytochrome P450-catalyzed activation of procarbazine
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Scheme 9.24 Acetylcholinesterase-catalyzed hydrolysis of acetylcholine
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Scheme 9.25 Phosphorylation of acetylcholinesterase by diisopropyl phosphorofluoridate
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Scheme 9.26 Reactivation of phosphorylated acetylcholinesterase by pralidoxime chloride
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Scheme 9.27 Carbamylation of acetylcholinesterase by neostigmine
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Scheme 9.28 S-Oxidation of clopidogrel, which initiates its inactivation of P2Y12
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Scheme 9.29 Cytochrome P450-catalyzed conversion of a cyclohexenone to a catechol
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Scheme 9.30 Reductive activation of sulfasalazine
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Scheme 9.31 Conversion of thiamin tetrahydrofurfuryl disulfide to thiamin
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Scheme 9.32 Reductive activation of ronidazole
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Scheme 9.33 Phosphoramidite-based prodrug for intracellular delivery of nucleotides
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Scheme 9.34 Nucleotide activation of 6-mercaptopurine
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Scheme 9.35 Metabolic activation of l-γ-glutamyl-l-dopa to dopamine
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Table 9.1
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Table 9.2
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Table 9.3
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Table 9.4
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