Ariëns Drug Design

Medicinal Chemistry: A Series of Monographs, Vol. 2
1. Auflage 2013
ISBN: 978-1-4832-1604-1
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 666 Seiten, Web PDF

Drug Design, Volume II covers the design of bioactive compounds interacting with enzymes and playing a role in enzyme synthesis. The book discusses the modulation of pharmacokinetics by molecular manipulation; the factors in the design of reversible and irreversible enzyme inhibitors; and the design of organophosphate and carbamate inhibitors of cholinesterases. The text also describes the design of reactivators for irreversibly blocked acetylcholinesterase; drug design based on the inhibition of protein synthesis in the context of susceptible enzymic reactions; as well as the role of enzymes and their synthesis as a target for antibiotic action. The rational design of antiviral agents; the design of penicillin; the design of peptide hormone analogs; as well as the advances in the design of diuretics are also considered. The book further tackles the design of biologically active steroids; the rational elements in the development of superior neuromuscular blocking agents; and the design of tumor-inhibitory alkylating drugs. Pharmacologists, chemists, and people involved in drug design will find the book invaluable.

Autoren/Hrsg.

Ariëns, E. J.

Inhaltsverzeichnis

1;Front Cover;1
2;Drug Design;4
3;Copyright Page;5
4;Table of Contents;6
5;List of Contributors;12
6;Preface;14
7;Introduction;16
8;Contents of Other Volumes;18
9;Chapter 1. Modulation of Pharmacokinetics by Molecular Manipulation;22
9.1;I. Introduction;23
9.2;II. The Significance of the Chemical Structure of Bioactive Compounds with Regard to the Various Processes Involved in Pharmacokinetics;24
9.3;III. Dissection of the Drug Molecule in Biofunctional Moieties;28
9.4;IV. Modulation of the Distribution of Pharmaca over the Various Compartments in Individual and Environmental Pharmacokinetics by Molecular Manipulation;33
9.5;V. Modulation of the Time–Concentration Relationship in the Distribution of Drugs by Molecular Manipulation;90
9.6;VI. Summary;138
9.7;REFERENCES;138
10;Chapter 2. Factors in the Design of Reversible and Irreversible Enzyme Inhibitors;150
10.1;I. Introduction;150
10.2;II. Mechanism of Action of Selected Drugs;154
10.3;III. Factors Involved in the Reversible Inhibition of Selected Enzymes;159
10.4;IV. Irreversible Inhibition of Selected Enzymes;167
10.5;V. Kinetics of Irreversible Enzyme Inactivation;170
10.6;VI. Tissue-Specific Irreversible Enzyme Inhibitors;176
10.7;VII. Summary;179
10.8;ACKNOWLEDGMENT;180
10.9;REFERENCES;180
11;Chapter 3. The Design of Organophosphate and Carbamate Inhibitors of Cholinesterases;182
11.1;I. Introduction;183
11.2;II. The Structure of the Active Zone of Cholinesterases;185
11.3;III. Design of Organophosphates;201
11.4;IV. Design of Carbamates;217
11.5;V. Future Approaches to Design of Anticholinesterases;227
11.6;REFERENCES;229
12;Chapter 4. The Design of Reactivators for Irreversibly Blocked Acetylcholinesterase;234
12.1;Text;234
12.2;REFERENCES;248
13;Chapter 5. Inhibition of Protein Biosynthesis: Its Significance in Drug Design;252
13.1;I. Introduction;252
13.2;II. Protein Biosynthesis;253
13.3;III. Inhibitors of Protein Synthesis;255
13.4;IV. Design of Antibacterial Agents;256
13.5;V. Design of Amebicidal Agents;257
13.6;VI. Design of Antitumor Agents;266
13.7;VII. Design of Emetic Agents;267
13.8;VIII. Design of Antiviral Agents;268
13.9;IX. Conclusions;268
13.10;ACKNOWLEDGMENT;268
13.11;REFERENCES;269
14;Chapter 6. Enzymes and Their Synthesis as a Target for Antibiotic Action;272
14.1;I. Introduction;272
14.2;II. Competitive Inhibitors of Enzymes;273
14.3;III. Irreversible Inhibitors or Enzymes as Antibacterial Agents;276
14.4;IV. Conclusion;280
14.5;REFERENCES;281
15;Chapter 7. The Rational Design of Antiviral Agents;282
15.1;I. Introduction;282
15.2;II. Approaches to the Design of Antiviral Agents;287
15.3;III. Conclusions;293
15.4;ACKNOWLEDGMENTS;293
15.5;REFERENCES;294
16;Chapter 8. Design of Penicillins;298
16.1;I. Introduction;298
16.2;II. Effect of Penicillins on Bacteria;303
16.3;III. Behavior of Penicillins in Vivo;321
16.4;IV. Derivatives Which Liberate Penicillins in Vivo;334
16.5;V. Concluding Remarks;335
16.6;ACKNOWLEDGMENT;336
16.7;REFERENCES;336
17;Chapter 9. The Design of Peptide Hormone Analogs;340
17.1;I. Introduction;340
17.2;II. Structural Aspects of Design;349
17.3;III. Biological Aspects and Practical Aims of Design;391
17.4;IV. Conclusions;422
17.5;ACKNOWLEDGMENTS;422
17.6;REFERENCES;422
18;Chapter 10. Recent Advances in the Design of Diuretics;442
18.1;I. Introduction;442
18.2;II. Mono- and Bicyclic Nitrogen Heterocycles;443
18.3;III. Sulfonamides and Disulfonamides;449
18.4;IV. a,ß-Unsaturated Ketone Derivatives;452
18.5;V. Miscellaneous Group;453
18.6;REFERENCES;455
19;Chapter 11. Design of Biologically Active Steroids;458
19.1;I. Introduction;458
19.2;II. Chemical Exploration and Pharmacological Screening;459
19.3;III. The Biological Study of the Cause of Disease;470
19.4;REFERENCES;472
20;Chapter 12. Rational Elements in the Development of Superior Neuromuscular Blocking Agents;474
20.1;I. Introduction;475
20.2;II. Grosser Morphological Features Influencing the Response to Neuromuscular Blocking Agents;477
20.3;III. The Anatomy and Physiology of the Neuromuscular Junction;479
20.4;IV. Mechanisms of Neuromuscular Blockade;503
20.5;V. Clinically Desirable Features in a Neuromuscular Blocking Agent;514
20.6;VI. Relationships between Chemical Constitution and Neuromuscular Blocking Activity;516
20.7;VII. Rational Applications of Structure–Action Relationships to the Synthesis of New Neuromuscular Blocking Agents;520
20.8;VIII· Conclusion;534
20.9;REFERENCES;535
21;Chapter 13. The Design of Tumor-Inhibitory Alkylating Drugs;552
21.1;I. Introduction;553
21.2;II. Types of Alkylating Groups;554
21.3;III. Sites of Reaction and Correlation with Biological Effects;557
21.4;IV. General Structural Considerations;558
21.5;V. Number of Reactive Centers;567
21.6;VI. Naturally Occurring Compounds and Analogs as Carriers of Alkylating Groups;570
21.7;VII. Dual Antagonists;578
21.8;VIII. Alkylating Agents Capable of Being Activated or Potentiated;579
21.9;IX. The Application of pH Differences;584
21.10;X. Compounds Designed for Intraarterial Infusion;586
21.11;XI. Conclusion;586
21.12;ACKNOWLEDGMENT;587
21.13;REFERENCES;587
22;Author Index;594
23;Subject Index;638