The organic chemistry of drug design and drug action:
Gespeichert in:
| Hauptverfasser: | , |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
Amsterdam ; Heidelberg [u.a.]
Elsevier Academic Press
2014
|
| Ausgabe: | 3. ed. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Klappentext |
| Beschreibung: | XVIII, 517 S. Ill., graph. Darst. |
| ISBN: | 9780123820303 |
Internformat
MARC
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| 100 | 1 | |a Silverman, Richard B. |d 1946- |e Verfasser |0 (DE-588)172375061 |4 aut | |
| 245 | 1 | 0 | |a The organic chemistry of drug design and drug action |c Richard B. Silverman ; Mark W. Holladay |
| 250 | |a 3. ed. | ||
| 264 | 1 | |a Amsterdam ; Heidelberg [u.a.] |b Elsevier Academic Press |c 2014 | |
| 300 | |a XVIII, 517 S. |b Ill., graph. Darst. | ||
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| 338 | |b nc |2 rdacarrier | ||
| 650 | 4 | |a Biyoorganik kimya | |
| 650 | 4 | |a Chimie bio-organique | |
| 650 | 7 | |a Chimie bio-organique |2 rasuqam | |
| 650 | 4 | |a Chimie pharmaceutique | |
| 650 | 7 | |a Chimie pharmaceutique |2 rasuqam | |
| 650 | 4 | |a Farmakolojik kimya | |
| 650 | 4 | |a Moleküler farmakoloji | |
| 650 | 4 | |a Médicaments - Conception | |
| 650 | 4 | |a Pharmacologie moléculaire | |
| 650 | 7 | |a Pharmacologie moléculaire |2 rasuqam | |
| 650 | 7 | |a Química farmacêutica |2 larpcal | |
| 650 | 4 | |a İlaçlar - Tasarım | |
| 650 | 4 | |a aPharmaceutical chemistry | |
| 650 | 4 | |a aBioorganic chemistry | |
| 650 | 4 | |a aMolecular pharmacology | |
| 650 | 4 | |a aDrugs |a xDesign | |
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Datensatz im Suchindex
| _version_ | 1804152327236485120 |
|---|---|
| adam_text | Preface to First Edition xiii
Preface to Second Edition xv
Preface to Third Edition xvii
1. Introduction 1
1.1. Overview 1
1.2. Drugs Discovered without Rational Design 2
1.2.1. Medicinal Chemistry Folklore 2
1.2.2. Discovery of Penicillins 3
1.2.3. Discovery of Librium 4
1.2.4. Discovery of Drugs through Metabolism
Studies 5
1.2.5. Discovery of Drugs through Clinical
Observations 6
1.3. Overview of Modern Rational Drug Design 7
1.3.1. Overview of Drug Targets 7
1.3.2. Identification and Validation of Targets
for Drug Discovery 9
1.3.3. Alternatives to Target-Based Drug
Discovery 10
1.3.4. Lead Discovery 11
1.3.5. Lead Modification (Lead Optimization) 12
1.3.5.1. Potency 12
1.3.5.2. Selectivity 12
1.3.5.3. Absorption, Distribution,
Metabolism, and Excretion
(ADME) 13
1.3.5.4. Intellectual Property Position 13
1.3.6. Drug Development 13
1.3.6.1. Preclinical Development 13
1.3.6.2. Clinical Development (Human
Clinical Trials) 14
1.3.6.3. Regulatory Approval to Market the
Drug 14
1.4. Epilogue 14
1.5. General References 15
1.6. Problems 16
References 16
2. Lead Discovery and Lead
Modification 19
2.1. Lead Discovery 20
2.1.1. General Considerations 20
2.1.2. Sources of Lead Compounds 20
2.1.2.1. Endogenous Ligands 20
2.1.2.2. Other Known Ligands 23
2.1.2.3. Screening of Compounds 24
2.1.2.3.1. Sources of Compounds for
Screening 26
2.1.2.3.1.1. Natural Products 26
2.1.2.3.1.2. Medicinal Chemistry
Collections and Other
Handcrafted
Compounds 27
2.1.2.3.1.3. High-Throughput
Organic Synthesis 27
2.1.2.3.1.3.1. Solid-Phase
Library Synthesis 27
2.1.2.3.1.3.2. Solution-Phase
Library Synthesis 30
2.1.2.3.1.3.3. Evolution of HTOS 31
2.1.2.3.2. Drug-Like, Lead-Like, and
Other Desirable Properties
of Compounds for
Screening 32
2.1.2.3.3. Random Screening 36
2.1.2.3.4. Targeted (or Focused)
Screening, Virtual Screening,
and Computational Methods
in Lead Discovery 36
2.1.2.3.4.1. Virtual Screening
Database 37
2.1.2.3.4.2. Virtual Screening
Hypothesis 37
2.1.2.3.5. Hit-To-Lead Process 43
2.1.2.3.6. Fragment-based Lead
Discovery 45
2.2, Lead Modification 54
2.2.1. Identification of the Active Part:
The Pharmacophore 55
2.2.2. Functional Group Modification 57
2.2.3. Structure-Activity Relationships 57
2.2.4. Structure Modifications to Increase
Potency, Therapeutic Index, and ADME
Properties 59
2.2.4.1. Homologation 60
2.2.4.2. Chain Branching 61
VII
Contents
2.2.43. Bioisosterism 62
2.2.4.4. Conformational Constraints and
Ring-Chain Transformations 66
2.2A.5. Peptidomimetics 68
2.2.5. Structure Modifications to Increase
Oral Bioavailability and Membrane
Permeability 72
2.2.5.1. Electronic Effects: The Hammett
Equation 72
2.2.5.2. Lipophilicity Effects 74
2.2.5.2.1. Importance of Lipophilicity 74
2.2.5.2.2. Measurement of
Lipophilicities 74
2.2.5.23. Computer Automation of
log P Determination 78
2.23.2.4. Membrane Lipophilicity 79
2.2.53. Balancing Potency of lonizable
Compounds with Lipophilicity and
Oral Bioavailability 79
2.23.4. Properties that Influence Ability
to Cross the Blood-Brain Barrier 81
2.2.53. Correlation of Lipophilicity with
Promiscuity and Toxicity 82
2.2.6. Computational Methods in Lead
Modification 83
2.2.6.1. Overview 83
2.2.6.2. Quantitative Structure-Activity
Relationships (QSARs) 83
2.2.6.2.1. Historical Overview. Steric
Effects: The Taft Equation and
Other Equations 83
2.2.6.2.2. Methods Used to Correlate
Physicochemical Parameters
with Biological Activity 84
2.2.6.2.2.1. Hansch Analysis: A Linear
Multiple Regression
Analysis 84
2.2.6.2.2.2. Manual Stepwise
Methods: Topliss
Operational Schemes
and Others 85
2.2.6.2.23. Batch Selection Methods:
Batchwise Topliss
Operational Scheme,
Cluster Analysis, and
Others 87
2.2.6.2.2A Free and Wilson or de
Novo Method 88
2.2.6.2.23. Computational Methods
for ADME Descriptors 89
2.2.63. Scaffold Hopping 89
2.2.6.4. Molecular Graphics-Based Lead
Modification 90
2.2.7. Epilogue 93
2.3. General References 95
2.4. Problems 102
References 106
3. Receptors 123
3.1. Introduction 123
3.2. Drug-Receptor Interactions 125
3.2.1. General Considerations 125
3.2.2. Important Interactions (Forces)
Involved in the Drug-Receptor
Complex 125
3.2.2.1. Covalent Bonds 126
3.2.2.2. Ionic (or Electrostatic)
Interactions 126
3.2.23. Ion-Dipole and Dipole-Dipole
Interactions 126
3.2.2.4. Hydrogen Bonds 126
3.2.23. Charge-Transfer Complexes 128
3.2.2.6. Hydrophobic Interactions 129
3.2.2.7. Cation-jrInteraction 130
3.2.2.8. Halogen Bonding 130
3.2.2.9. van der Waals or London
Dispersion Forces 130
3.2.2.10. Conclusion 131
3.2.3. Determination of Drug-Receptor
Interactions 131
3.2.4. Theories for Drug-Receptor
Interactions 134
3.2.4.1. Occupancy Theory 134
3.2.4.2. Rate Theory 137
3.2.43. Induced-Fit Theory 137
3.2.4.4. Macromolecular Perturbation
Theory 137
3.2.43. Activation-Aggregation Theory 138
3.2.4.6. The Two-State (Multistate) Model
of Receptor Activation 13 8
3.2.5. Topographical and Stereochemical
Considerations 139
3.23.1. Spatial Arrangement of Atoms 139
3.23.2. Drug and Receptor Chirality 140
3.2.53. Diastereomers 145
3.23.4. Conformational Isomers 146
3.233. Atropisomers 149
3.23.6. Ring Topology 151
3.2.6. Case History of the
Pharmacodynamically Driven Design
of a Receptor Antagonist: Cimetidine 151
3.2.7. Case History of the
Pharmacokinetically Driven Design
of Suvorexant 156
3.3. General References 157
3.4. Problems 157
References 159
Contents
4. Enzymes
165
4.1. Enzymes as Catalysts 165
4.1.1. What are Enzymes? 165
4.1.2. How do Enzymes Work? 166
4.1.2.1. Specificity of Enzyme-Catalyzed
Reactions 167
4.1.2.1.1. Binding Specificity 167
4.1.2.1.2. Reaction Specificity 168
4.1.2.2. Rate Acceleration 168
4.2. Mechanisms of Enzyme Catalysis 169
4.2.1. Approximation 169
4.2.2. Covalent Catalysis 170
4.2.3. General Acid-Base Catalysis 170
4.2.4. Electrostatic Catalysis 172
4.2.5. Desolvation 173
4.2.6. Strain or Distortion 173
4.2.7. Example of the Mechanisms of
Enzyme Catalysis 174
4.3. Coenzyme Catalysis 175
4.3.1. Pyridoxal 5 -Phosphate 178
4.3.1.1. Racemases 178
4.3.1.2. Decarboxylases 180
4.3.1.3. Aminotransferases (Formerly
Transaminases) 180
4.3.1.4. PLP-Dependent /5-Elimination 184
4.3.2. Tetrahydrofolate and Pyridine
Nucleotides 184
4.3.3. Flavin 189
4.3.3.1. Two-Electron (Carbanion)
Mechanism 190
4.3.3.2. Carbanion Followed by Two
One-Electron Transfers 190
4.33.3. One-Electron Mechanism 192
43.3.4. Hydride Mechanism 192
43.4. Heme 192
43.5. Adenosine Triphosphate and
Coenzyme A 195
4.4. Enzyme Catalysis in Drug Discovery 196
4.4.1. Enzymatic Synthesis of Chiral Drug
Intermediates 196
4.4.2. Enzyme Therapy 198
4.5. General References 198
4.6. Problems 199
References 202
5.2.2.1.1. Epidermal Growth Factor
Receptor Tyrosine Kinase
as a Target for Cancer
5.2.2.1.2. Discovery and Optimization
of EGFR Inhibitors
5.2.2.2. Stabilization of an Inactive
Conformation: Imatinib, an
Antileukemia Drug
5.2.2.2.1. The Target: Bcr-Abl, a
Constitutively Active
Kinase
5.2.2.2.2. Lead Discovery and
Modification
5.2.2.23. Binding Mode of Imatinib
to Abl Kinase
5.2.2.2A Inhibition of Other Kinases
by Imatinib
5.2.23. Alternative Substrate Inhibition:
Sulfonamide Antibacterial Agents
(Sulfa Drugs)
5.2.23.1. Lead Discovery
5.2.23.2. Lead Modification
5.2.23.3. Mechanism of Action
5.23. Transition State Analogs and
Multisubstrate Analogs
5.23.1. Theoretical Basis
5.23.2. Transition State Analogs
5.23.2.1. Enalaprilat
5.23.2.2. Pentostatin
5.23.2.3. Forodesine and
DADMe-lmmH
5.23.2.4. Multisubstrate Analogs
5.2.4. Slow, Tight-Binding Inhibitors
5.2.4.1. Theoretical Basis
5.2.4.2. Captopril, Enalapril, Lisinopril,
and Other Antihypertensive Drugs
5.2.4.2.1. Humoral Mechanism for
Hypertension
5.2.4.2.2. Lead Discovery
5.2.4.23. Lead Modification and
Mechanism of Action
5.2A2.4. Dual-Acting Drugs:
Dual-Acting Enzyme
Inhibitors
5.2.43. Lovastatin (Mevinolin) and
211
212
213
213
214
215
216
217
217
217
217
219
219
220
220
221
222
223
225
225
225
225
226
226
230
Simvastatin,
Antihypercholesterolemic Drugs 232
Enzyme Inhibition and Inactivation 207 5.2.43.1. Cholesterol and Its Effects 232
5.1. Why Inhibit an Enzyme? 208 5.2.43.2. Lead Discovery 232
5.2. Reversible Enzyme Inhibitors 210 5.2.43.3. Mechanism of Action 233
5.2.1. Mechanism of Reversible Inhibition 210 5.2.43.4. Lead Modification 234
5.2.2. Selected Examples of Competitive 5.2 A4. Saxagliptin, a Dipeptidyl
Reversible Inhibitor Drugs 211 Peptidase-4 Inhibitor and
5.2.2.1. Simple Competitive Inhibition 211 Antidiabetes Drug 234
Contents
5.2.5. Case History of Rational Drug Design
of an Enzyme Inhibitor: Ritonavir 235
5.2.5.1. Lead Discovery 235
5.2.5.2. Lead Modification 236
5.3. Irreversible Enzyme Inhibitors 238
5.3.1. Potential of Irreversible Inhibition 238
5.3.2. Affinity Labeling Agents 240
5.3.2.1. Mechanism of Action 240
5.3.2.2. Selected Affinity Labeling
Agents 241
5.3.2.2.1. Penicillinsand
Cephalosporins/
Cephamycins 241
53.2.2.2. Aspirin 243
5.3.3. Mechanism-Based Enzyme
Inactivators 247
5.3.3.1. Theoretical Aspects 247
5.33.2. Potential Advantages in Drug
Design Relative to Affinity
Labeling Agents 247
5.33.3. Selected Examples of
Mechanism-Based Enzyme
Inactivators 248
5.333.1. Vigabatrin, an
Anticonvulsant Drug 248
5.3.33.2. Eflornithine, an
Antiprotozoal Drug and
Beyond 250
5.3.33.3. Tranylcypromine, an
Antidepressant Drug 253
5.3.33.4. Selegiline (l-Deprenyl) and
Rasagiline: Antiparkinsonian
Drugs 254
5.333.5. 5-Fluoro-2 -deoxyuridylate,
Floxuridine, and
5-Fluorouracil: Antitumor
Drugs 256
5.4. General References 258
5.5. Problems 261
References 265
6. DNA-Interactive Agents 275
6.1. Introduction 275
6.1.1. Basis for DNA-Interactive Drugs 275
6.1.2. Toxicity of DNA-Interactive Drugs 276
6.1.3. Combination Chemotherapy 276
6.1.4. Drug Interactions 277
6.1.5. Drug Resistance 277
6.2. DNA Structure and Properties 277
6.2.1. Basis for the Structure of DNA 277
6.2.2. BaseTautomerization 279
6.23. DNA Shapes 280
6.2.4. DNA Conformations 286
6.3. Classes of Drugs that Interact with DNA 287
6.3.1. Reversible DNA Binders 288
63.1.1. External Electrostatic Binding 289
63.1.2. Groove Binding 289
6.3.13. Intercalation andTopoisomerase-
Induced DNA Damage 290
63.13.1. Amsacrine, an Acridine
Analog 292
6.3.1.3.2. Dactinomycin, the Parent
Actinomycin Analog 293
63.1.3.3. Doxorubicin (Adriamycin)
and Daunorubicin
(Daunomycin),
Anthracycline Antitumor
Antibiotics 294
63.13.4. S/s-intercalatingAgents 295
6.3.2. DNAAlkylators 295
63.2.1. Nitrogen Mustards 295
63.2.1.1. Lead Discovery 295
63.2.1.2. Chemistry of Alkylating
Agents 296
63.2.13. Lead Modification 297
63.2.2. Ethylenimines 299
6.3.23. Methanesulfonates 299
63.2.4. (+)-CC-1065 and Duocarmycins 300
63.2.5. Metabolically Activated
Alkylating Agents 301
63.2.5.1. Nitrosoureas 301
63.2.5.2. Triazene Antitumor Drugs 303
63.2.53. Mitomycin C 303
63.2.5.4. Leinamycin 305
6.3.3. DNA Strand Breakers 307
6.33.1. AnthracyclineAntitumor
Antibiotics 307
63.3.2. Bleomycin 308
63.3.3. Tirapazamine 310
63.3.4. Enediyne Antitumor Antibiotics 311
633.4.1. Esperamicins and
Calicheamicins 313
633.4.2. DynemicinA 314
63.3.4.3. Neocarzinostatin (Zinostatin) 314
6.33.5. Sequence Specificity for
DNA-Strand Scission 317
6.4. General References 319
6.5. Problems 319
References 320
7. Drug Resistance and Drug Synergism 333
7.1. Drug Resistance 333
7.1.1. What is Drug Resistance? 333
7.1.2. Mechanisms of Drug Resistance 334
7.1.2.1. Altered Target Enzyme or
Receptor 334
Contents
7.1.2.2. Overproduction of the Target
Enzyme or Receptor 340
7.1.2.3. Overproduction of the Substrate
or Ligand for the Target Protein 341
7.1.2.4. Increased Drug-Destroying
Mechanisms 341
7.1.2.5. Decreased Prodrug-Activating
Mechanism 344
7.1.2.6. Activation of New Pathways
Circumventing the Drug Effect 344
7.1.2.7. Reversal of Drug Action 344
7.1.2.8. Altered Drug Distribution to the
Site of Action 346
7.2. Drug Synergism (Drug Combination) 346
7.2.1. What is Drug Synergism? 346
7.2.2. Mechanisms of Drug Synergism 346
7.2.2.1. Inhibition of a Drug-Destroying
Enzyme 346
722.2. Sequential Blocking 348
7223. Inhibition of Targets in Different
Pathways 349
7.2.2.4. Efflux Pump Inhibitors 350
7.2.2.5. Use of Multiple Drugs for the
Same Target 350
7.3. General References 352
7.4. Problems 352
References 352
8. Drug Metabolism 357
8.1. Introduction 357
8.2. Synthesis of Radioactive Compounds 359
8.3. Analytical Methods in Drug Metabolism 361
8.3.1. Sample Preparation 361
8.3.2. Separation 361
8.3.3. Identification 362
8.3.4. Quantification 363
8.4. Pathways for Drug Deactivation and
Elimination 363
8.4.1. Introduction 363
8.4.2. Phase I Transformations 365
8.4.2.1. Oxidative Reactions 365
8.4.2.1.1. Aromatic Hydroxylation 368
8.4.2.1.2. Alkene Epoxidation 373
8.4.2.1.3. Oxidations of Carbons
Adjacent to sp2 Centers 373
8.4.2.1.4. Oxidation at Aliphatic and
Alicyclic Carbon Atoms 374
8.4.2.1.5. Oxidations of
Carbon-Nitrogen Systems 375
8.4.2.1.6. Oxidations of
Carbon-Oxygen Systems 385
8.4.2.1.7. Oxidations of Carbon-Sulfur
Systems 385
8.4.2.1.8. Other Oxidative Reactions 387
8.4.2.1.9. Alcohol and Aldehyde
Oxidations 387
8.4.2.2. Reductive Reactions 388
8.4.2.2.1. Carbonyl Reduction 388
8.4.2.2.2. Nitro Reduction 389
8.4.2.2.3. Azo Reduction 390
8.4.2.2.4. Azido Reduction 390
8.4.2.2.5. Tertiary Amine Oxide
Reduction 390
8.4.2.2.6. Reductive Dehalogenation 391
8.4.2.3. Carboxylation Reaction 391
8.4.2.4. Hydrolytic Reactions 391
8.4.3. Phase II Transformations: Conjugation
Reactions 393
8.4.3.1. Introduction 393
8.4.3.2. Glucuronic Acid Conjugation 395
8.4.3.3. Sulfate Conjugation 397
8.4.3.4. Amino Acid Conjugation 398
8.4.3.5. Glutathione Conjugation 399
8.4.3.6. Water Conjugation 400
8.43.7. Acetyl Conjugation 400
8.43.8. Fatty Acid and Cholesterol
Conjugation 403
8.43.9. Methyl Conjugation 403
8.4.4. Toxicophores and Reactive
Metabolites (RMs) 405
8.4.5. Hard and Soft (Antedrugs) Drugs 405
8.5. General References 407
8.6. Problems 408
References 411
9. Prodrugs and Drug Delivery
Systems 423
9.1. Enzyme Activation of Drugs 423
9.1.1. Utility of Prodrugs 424
9.1.1.1. Aqueous Solubility 424
9.1.1.2. Absorption and Distribution 424
9.1.1.3. Site Specificity 424
9.1.1.4. Instability 424
9.1.1.5. Prolonged Release 424
9.1.1.6. Toxicity 424
9.1.1.7. Poor Patient Acceptability 424
9.1.1.8. Formulation Problems 424
9.1.2. Types of Prodrugs 424
9.2. Mechanisms of Drug Inactivation 425
9.2.1. Carrier-Linked Prodrugs 425
9.2.1.1. Carrier Linkages for Various
Functional Groups 425
9.2.1.1.1. Alcohols, Carboxylic Acids,
and Related 425
9.2.1.1.2. Amines and Amidines 427
9.2.1.13. Sulfonamides 428
9.2.1.1.4. Carbonyl Compounds 428
Contents
9.2.1.2. Examples of Carrier-Linked
Bipartite Prodrugs 428
9.2.1.2.1. Prodrugs for Increased
Water Solubility 428
9.2.1.2.2. Prodrugs for Improved
Absorption and Distribution 429
9.2.1.2.3. Prodrugs for Site Specificity 429
9.2.1.2.4. Prodrugs for Stability 433
9.2.1.2.5. Prodrugs for Slow and
Prolonged Release 434
9.2.1.2.6. Prodrugs to Minimize
Toxicity 434
9.2.1.2.7. Prodrugs to Encourage
Patient Acceptance 435
9.2.1.2.8. Prodrugs to Eliminate
Formulation Problems 435
9.2.1.3. Macromolecular Drug Carrier
Systems 435
9.2.1.3.1. General Strategy 435
9.2.1.3.2. Synthetic Polymers 436
9.2.1.3.3. Poly(a-Amino Acids) 436
9.2.1.3.4. Other Macromolecular
Supports 438
9.2.1.4. Tripartite Prodrugs 438
9.2.1.5. Mutual Prodrugs (also called
Codrugs) 443
9.2.2. Bioprecursor Prodrugs 443
9.2.2.1. Origins 443
9.2.2.2. Proton Activation: An Abbreviated
Case History of the Discovery of
Omeprazole 444
9.2.2.3. Hydrolytic Activation 445
9.2.2.4. Elimination Activation 445
9.2.2.5. Oxidative Activation 446
9.2.2.5.1. N- and O-Dealkylations 446
92.2.5.2. Oxidative Deamination 447
9.2.2.5.3. N-Oxidation 448
9.2.2.5.4. 5-Oxidation 450
9.2.2.5.5. Aromatic Hydroxylation 451
9.2.2.5.6. Other Oxidations 451
9.2.2.6. Reductive Activation 452
9.2.2.6.1. Azo Reduction 452
9.2.2.6.2. Azido Reduction 453
9.2.2.6.3. Sulfoxide Reduction 453
9.2.2.6A Disulfide Reduction 453
9.2.2.6.5. Nitro Reduction 454
92.2.7. Nucleotide Activation 454
9.2.2.8. Phosphorylation Activation 455
9.22.9. Sulfation Activation 457
9.2.2.10. Decarboxylation Activation 457
9.3. General References 459
9.4. Problems 459
References 461
Appendix 469
Index 507
Please look for the Student/companion site at http://booksite.elsevier.com/9780123820303
Please look for the Instructor site (coming soon) at http://textbooks.eisevier.com/web/manuals.aspx?isbn=9780123820303
e Grganic Chemistry of Drug Design and Drug AetiongThird Edition, represents a unique approach to medieina
chemistry based on physical organic chemical principles and reaction mechanisms that rationalize drug action, which
allows the reader to extrapolate those core principles and mechanisms to many related classes of drug molecules. This
new edition reflects significant changes in the process of drug design over the last decade. It preserves the successful
approach of the previous editions while including significant changes in format and coverage.
■New to11 h is ©d ition
# Updates to all chapters, including new examples and references
• Chapter 1 (Introduction): Completely rewritten and expanded as an overview of topics discussed in detail
throughout the book
♦ Chapter 2 (Lead Discovery and Lead Modification): Sections on sources of compounds for screening including
library collections, virtual screening, and computational methods, as well as hit-to-lead and scaffold hopping;
If expanded sections on sources of lead compounds, fragment-based lead discovery, and molecular graphics;
and deemphasized solid-phase synthesis and combinatorial chemistry
• Chapters (Recediprs): Drug-receptor interactions, cation-;* and halogen bonding; atropisomers; case history of the
insomnia drug suvorexant ■ : ||:; ; p . v 4.1 I ‘ ‘
• Chapter 4 (Enzymes): Expanded sections on enzyme catalysis in drdg discovery and enzyme synthesis
♦ Chapter 5 (Enzyme Inhibition and Inactivation): New case histories:
lllill for competitive inhibition, the epidermal growth factor receptor tyrosine kinase inhibitor, erlotinib and Abelson
kinase inhibitor, imatinib
• for transition state analogue inhibition, the purine nucleoside phosphorylase inhibitors, forodesine and
DADMe-lmmH, as welt as the mechanism of the multisubstrate analog inhibitor isoniazid
• for slow, tiiht-binding inhibition, the dipeptidyl peptidase-4 inhibitor, saxagliptin
s Chapter 7 (Drug Resistance and Drug Synergism): This new chapter includes topics taken from two chapters in the
previous edition, with many new examples
« Chapter 8 (Drug Metabolism): Discussions of toxicophotes and reactive metabolites
Chapter 9 (Prodrugs and Drug Delivery Systems): Discussion of antibody-drug conjugates
...
ill
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«8!
|
| any_adam_object | 1 |
| author | Silverman, Richard B. 1946- Holladay, Mark W. |
| author_GND | (DE-588)172375061 |
| author_facet | Silverman, Richard B. 1946- Holladay, Mark W. |
| author_role | aut aut |
| author_sort | Silverman, Richard B. 1946- |
| author_variant | r b s rb rbs m w h mw mwh |
| building | Verbundindex |
| bvnumber | BV041947765 |
| callnumber-first | R - Medicine |
| callnumber-label | RS403 |
| callnumber-raw | RS403 |
| callnumber-search | RS403 |
| callnumber-sort | RS 3403 |
| callnumber-subject | RS - Pharmacy |
| classification_rvk | VS 5350 |
| classification_tum | CHE 893f MED 960f MED 970f |
| ctrlnum | (OCoLC)882936480 (DE-599)BSZ407409882 |
| dewey-full | 615/.19 |
| dewey-hundreds | 600 - Technology (Applied sciences) |
| dewey-ones | 615 - Pharmacology and therapeutics |
| dewey-raw | 615/.19 |
| dewey-search | 615/.19 |
| dewey-sort | 3615 219 |
| dewey-tens | 610 - Medicine and health |
| discipline | Chemie / Pharmazie Chemie Medizin |
| edition | 3. ed. |
| format | Book |
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| id | DE-604.BV041947765 |
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| indexdate | 2024-07-10T01:08:57Z |
| institution | BVB |
| isbn | 9780123820303 |
| language | English |
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| physical | XVIII, 517 S. Ill., graph. Darst. |
| publishDate | 2014 |
| publishDateSearch | 2014 |
| publishDateSort | 2014 |
| publisher | Elsevier Academic Press |
| record_format | marc |
| spelling | Silverman, Richard B. 1946- Verfasser (DE-588)172375061 aut The organic chemistry of drug design and drug action Richard B. Silverman ; Mark W. Holladay 3. ed. Amsterdam ; Heidelberg [u.a.] Elsevier Academic Press 2014 XVIII, 517 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Biyoorganik kimya Chimie bio-organique Chimie bio-organique rasuqam Chimie pharmaceutique Chimie pharmaceutique rasuqam Farmakolojik kimya Moleküler farmakoloji Médicaments - Conception Pharmacologie moléculaire Pharmacologie moléculaire rasuqam Química farmacêutica larpcal İlaçlar - Tasarım aPharmaceutical chemistry aBioorganic chemistry aMolecular pharmacology aDrugs xDesign Naturstoffchemie (DE-588)4171332-1 gnd rswk-swf Arzneimittelentwicklung (DE-588)4143176-5 gnd rswk-swf Pharmakokinetik (DE-588)4115557-9 gnd rswk-swf Physiologische Chemie (DE-588)4076124-1 gnd rswk-swf Arzneimittelforschung (DE-588)4003120-2 gnd rswk-swf Molekularpharmakologie (DE-588)4170397-2 gnd rswk-swf Arzneimitteldesign (DE-588)4278218-1 gnd rswk-swf Pharmazeutische Chemie (DE-588)4132158-3 gnd rswk-swf 1\p (DE-588)4123623-3 Lehrbuch gnd-content Arzneimittelentwicklung (DE-588)4143176-5 s DE-604 Pharmazeutische Chemie (DE-588)4132158-3 s Arzneimitteldesign (DE-588)4278218-1 s 2\p DE-604 Physiologische Chemie (DE-588)4076124-1 s Arzneimittelforschung (DE-588)4003120-2 s 3\p DE-604 Molekularpharmakologie (DE-588)4170397-2 s 4\p DE-604 Naturstoffchemie (DE-588)4171332-1 s 5\p DE-604 Pharmakokinetik (DE-588)4115557-9 s 6\p DE-604 Holladay, Mark W. Verfasser aut Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027390797&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis Digitalisierung UB Regensburg - ADAM Catalogue Enrichment application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027390797&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA Klappentext 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 3\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 4\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 5\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 6\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Silverman, Richard B. 1946- Holladay, Mark W. The organic chemistry of drug design and drug action Biyoorganik kimya Chimie bio-organique Chimie bio-organique rasuqam Chimie pharmaceutique Chimie pharmaceutique rasuqam Farmakolojik kimya Moleküler farmakoloji Médicaments - Conception Pharmacologie moléculaire Pharmacologie moléculaire rasuqam Química farmacêutica larpcal İlaçlar - Tasarım aPharmaceutical chemistry aBioorganic chemistry aMolecular pharmacology aDrugs xDesign Naturstoffchemie (DE-588)4171332-1 gnd Arzneimittelentwicklung (DE-588)4143176-5 gnd Pharmakokinetik (DE-588)4115557-9 gnd Physiologische Chemie (DE-588)4076124-1 gnd Arzneimittelforschung (DE-588)4003120-2 gnd Molekularpharmakologie (DE-588)4170397-2 gnd Arzneimitteldesign (DE-588)4278218-1 gnd Pharmazeutische Chemie (DE-588)4132158-3 gnd |
| subject_GND | (DE-588)4171332-1 (DE-588)4143176-5 (DE-588)4115557-9 (DE-588)4076124-1 (DE-588)4003120-2 (DE-588)4170397-2 (DE-588)4278218-1 (DE-588)4132158-3 (DE-588)4123623-3 |
| title | The organic chemistry of drug design and drug action |
| title_auth | The organic chemistry of drug design and drug action |
| title_exact_search | The organic chemistry of drug design and drug action |
| title_full | The organic chemistry of drug design and drug action Richard B. Silverman ; Mark W. Holladay |
| title_fullStr | The organic chemistry of drug design and drug action Richard B. Silverman ; Mark W. Holladay |
| title_full_unstemmed | The organic chemistry of drug design and drug action Richard B. Silverman ; Mark W. Holladay |
| title_short | The organic chemistry of drug design and drug action |
| title_sort | the organic chemistry of drug design and drug action |
| topic | Biyoorganik kimya Chimie bio-organique Chimie bio-organique rasuqam Chimie pharmaceutique Chimie pharmaceutique rasuqam Farmakolojik kimya Moleküler farmakoloji Médicaments - Conception Pharmacologie moléculaire Pharmacologie moléculaire rasuqam Química farmacêutica larpcal İlaçlar - Tasarım aPharmaceutical chemistry aBioorganic chemistry aMolecular pharmacology aDrugs xDesign Naturstoffchemie (DE-588)4171332-1 gnd Arzneimittelentwicklung (DE-588)4143176-5 gnd Pharmakokinetik (DE-588)4115557-9 gnd Physiologische Chemie (DE-588)4076124-1 gnd Arzneimittelforschung (DE-588)4003120-2 gnd Molekularpharmakologie (DE-588)4170397-2 gnd Arzneimitteldesign (DE-588)4278218-1 gnd Pharmazeutische Chemie (DE-588)4132158-3 gnd |
| topic_facet | Biyoorganik kimya Chimie bio-organique Chimie pharmaceutique Farmakolojik kimya Moleküler farmakoloji Médicaments - Conception Pharmacologie moléculaire Química farmacêutica İlaçlar - Tasarım aPharmaceutical chemistry aBioorganic chemistry aMolecular pharmacology aDrugs xDesign Naturstoffchemie Arzneimittelentwicklung Pharmakokinetik Physiologische Chemie Arzneimittelforschung Molekularpharmakologie Arzneimitteldesign Pharmazeutische Chemie Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027390797&sequence=000003&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027390797&sequence=000004&line_number=0002&func_code=DB_RECORDS&service_type=MEDIA |
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