Chapter 09 Prodrugs and Drug Delivery Systems

Copyright © 2014 Elsevier Inc. All rights reserved. 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 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.1 Protecting group analogy for a prodrug Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.2 Intramolecular catalysis of succinate esters Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.3 Bioreductively activated carrier-linked prodrug Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.4 Liver metabolism of drugs containing phosphate and phosphonate moieties Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.5 Nitrogen mustard activation by carboxypeptidase G2 for use with ADEPT Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.6 Catalytic antibody 38C2 activation of a doxorubicin prodrug by tandem retro-aldol/retro-Michael reactions for use with ADAPT Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.7 Nitroreductase activation of a prodrug for use with GDEPT Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.8 Antibody-targeted chemotherapy, a prodrug for calicheamicin Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.9 Tripartite prodrugs Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.10 Double prodrug concept Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.11 Tripartite prodrugs of ampicillin Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.12 Redox drug delivery system to cross the blood–brain barrier Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.13 Redox tripartite drug delivery system Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.14 Redox tripartite drug delivery of β-lactam antibiotics Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.15 Activation of peptidyl derivatives of 5-fluorouracil Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.16 Tripartite macromolecular drug delivery system Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.17 Mechanism of inactivation of H+,K+-ATPase by omeprazole Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.18 Conversion of leinamycin into a series of prodrugs Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.19 Hydrolytic activation of leinamycin prodrugs Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.20 Activation of leflunomide to the active drug Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.21 Bioprecursor prodrugs for alprazolam and triazolam Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.22 Cytochrome P450-catalyzed activation of cyclophosphamide Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.23 Cytochrome P450-catalyzed activation of procarbazine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.24 Acetylcholinesterase-catalyzed hydrolysis of acetylcholine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.25 Phosphorylation of acetylcholinesterase by diisopropyl phosphorofluoridate Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.26 Reactivation of phosphorylated acetylcholinesterase by pralidoxime chloride Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.27 Carbamylation of acetylcholinesterase by neostigmine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.28 S-Oxidation of clopidogrel, which initiates its inactivation of P2Y12 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.29 Cytochrome P450-catalyzed conversion of a cyclohexenone to a catechol Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.30 Reductive activation of sulfasalazine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.31 Conversion of thiamin tetrahydrofurfuryl disulfide to thiamin Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.32 Reductive activation of ronidazole Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.33 Phosphoramidite-based prodrug for intracellular delivery of nucleotides Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.34 Nucleotide activation of 6-mercaptopurine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 9.35 Metabolic activation of l-γ-glutamyl-l-dopa to dopamine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 9.1 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 9.2 Copyright © 2014 Elsevier Inc. All rights reserved.

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Copyright © 2014 Elsevier Inc. All rights reserved. Table 9.1 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 9.2 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 9.3 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 9.4 Copyright © 2014 Elsevier Inc. All rights reserved.