药物化学 英汉双语教材 英中双语注解版PDF电子书下载

Chapter 1　Drug Discovery,Design and Development 1

1.1 Drug Discovery 1

1.1.1 ADrug Discovery Without a Lead 2

1.1.2 Lead Discovery 5

1.2 Lead Modification 9

1.2.1 Identification of the Active Part:The Pharmacophore 9

1.2.2 Structure Modifications to Increase Potency and the Therapeutic Index 12

1.3 Structure-Activity Relationships 21

1.4 Quantitative Structure-Activity Relationships 23

1.4.1 Methods Used to Correlate Physicochemical Parameters with Biological Activity:2D-QSAR 24

1.4.2 Computer-Based Methods of QSAR Related to Receptor Binding:3D-QSAR 26

1.4.3 Structure-Based Drug Design 29

1.5 New Drug Development 36

1.5.1 General Process of New Drug Development 36

1.5.2 Preclinical Development and Investigational New Drug Application 38

1.6 Problems 39

本章重点内容 40

Chapter 2 Receptors 42

2.1 Drug-Receptor Interactions 42

2.1.1 Interactions(Forces)Involved in the Drug-Receptor Complex 42

2.2 Theories for Drug-Receptor Interactions 51

2.2.1 Occupancy Theory 51

2.2.2 Rate Theory 53

2.2.3 Induced-Fit Theory 53

2.2.4 Macromolecular Perturbation Theory 54

2.2.5 Activation-Aggregation Theory 55

2.2.6 The Two-State(Multistate)Model of Receptor Activation 55

2.3 Topographical and Stereochemical Considerations 57

2.3.1 Spatial Arrangement of Atoms 57

2.3.2 Drug and Receptor Chirality 58

2.3.3 Geometric Isomers(Diastereomers) 69

2.3.4 Conformational Isomers 70

2.3.5 Ring Topology 76

2.4 Problems 77

本章重点内容 80

Chapter 3 Enzymes and Enzyme Inhibition 83

3.1 Enzymes 83

3.1.1 Enzymes as Catalysts 83

3.1.2 Mechanisms of Enzyme Catalysis 88

3.1.3 Coenzyme Catalysis 92

3.2 Enzyme Inhibition 95

3.2.1 Enzyme Inhibitors in Medicine 95

3.2 2 Design of Enzyme Inhibitors 96

3.3 Reversible Enzyme Inhibitors 99

3.3.1 Mechanism of Reversible Inhibition 99

3.3.2 Selected Examples of Competitive Reversible Inhibitor Drugs 101

3.3.3 Transition State Analogs 103

3.3.4 Multisubstrate Analogs 105

3.3.5 Slow,Tight-Binding Inhibitors 106

3.4 Irreversible Enzyme Inhibitors 108

3.4.1 Affinity Labeling Agents 108

3.4.2 Mechanism-Based Enzyme Inactivators 111

3.5 Problems 114

本章重点内容 116

Chapter 4 Drug Metabolism 118

4.1 Introduction 118

4.1.1 Definition of Drug Metabolism 118

4.1.2 Site of Drug Metabolism and First-Pass Effect 118

4.1.3 Purpose of Drug Metabolism Studies 119

4.1.4 Function of Drug Metabolism and Categories of Drug Metabolism Reaction 120

4.2 Phase Ⅰ Transformations 121

4.2.1 Oxidative Reactions 121

4.2.2 Reductive Reactions 135

4.2.3 Carboxylation Reaction 139

4.2.4 Hydrolytic Reactions 140

4.3 Phase Ⅱ Transformations:Conjugation Reactions 141

4.3.1 Introduction 141

4.3.2 Glucuronic Acid Conjugation 143

4.3.3 Sulfate Conjugation 145

4.3.4 Amino Acid Conjugation 146

4.3.5 Glutathione Conjugation 148

4.3.6 Acetyl Conjugation 150

4.3.7 Other Conjugation 152

4.4 Problems 153

本章重点内容 155

Chapter 5 Prodrugs and Drug Delivery Systems 157

5.1 Enzyme Activation of Drugs 157

5.1.1 Utility of Prodrugs 157

5.1.2 Types of Prodrugs 159

5.2 Mechanisms of Drug Activation 160

5.2.1 Carrier-Linked Prodrugs 160

5.2.2 Bioprecursor Prodrugs 177

5.3 Problems 189

本章重点内容 190

Chapter 6 Central Nervous System Drugs 191

6.1 Schizophrenia 191

6.1.1 Introduction 191

6.1.2 Disease Basis 191

6.1.3 Current Treatment 193

6.1.4 Stucture-activity Relationship of Tricyclic Anti-psychotics 197

6.1.5 Unmet Medical Needs 201

6.1.6 New Research Areas 202

6.2 Affective Disorders:Depression and Bipolar Disease 203

6.2.1 Introduction 203

6.2 2 Disease Basis 204

6.2.3 Current Treatment 204

6.2.4 Stucture-activity Relationship of Tricyclic antidepressants 209

6.2.5 Unmet Medical Needs 211

6.2.6 New Research Areas 211

6.3 Anxiety 212

6.3.1 Introduction 212

6.3.2 Disease Basis 213

6.3.3 Current Treatments 213

6.3.4 Stucture-activity Relationship of Benzodiazepines 216

6.3.5 New Research Areas 218

6.4 Sleep Disorders 218

6.4.1 Introduction 218

6.4.2 Disease Basis 219

6.4.3 Current Treatment 219

6.4.4 Unmet Medical Needs 225

6.4.5 New Research Areas 225

6.5 Epilepsy 225

6.5.1 Introduction 225

6.5.2 Disease Basis 226

6.5.3 Current Treatment 226

6.5.4 Stucture-activity Relationship on homotypical drugs of Barbiturates 228

6.5.5 Unmet Medical Needs 229

6.5.6 New Research Areas 230

6.6 Addiction 231

6.6.1 Introduction 231

6.6.2 Disease Basis 233

6.6.3 Current Treatment 234

6.6.4 Unmet Medical Needs 236

6.6.5 New Research Areas 236

6.7 Neurodegeneration 236

6.7.1 Overview 236

6.7.2 Alzheimer's Disease 238

6.7.3 Parkinson's Disease 248

6.7.4 Future Aspects 253

6.8 Problems 254

References 254

本章重点内容 255

Chapter 7 Analgesics and Anesthetics 258

7.1 Analgesics 258

7.1.1 Introduction 258

7.1.2 Opioid Receptor 260

7.1.3 Endogenous Opioid Peptides 260

7.1.4 Morphine and Related Opioids 261

7.1.5 Synthesis Analgesics 265

7.1.6 Opioid Agonist/Antagonists and Partial Agonists 270

7.1.7 Opioid Antagonists 270

7.1.8 Structure-Activity Relationships 271

7.1.9 Unmet Medical Needs 273

7.1.10 New Research Areas 273

7.2 Anesthetics 274

7.2.1 General Anesthetics 274

7.2.2 Local Anesthetics 279

7.2.3 Unmet Medical Needs 287

7.2.4 New Research Areas 288

7.3 Problem 289

本章重点内容 290

Chapter 8 Drugs for Metabolic Syndrome Treatment 292

8.1 Introduction 292

8.1.1 Definition of Metabolic Syndrome(Mats) 292

8.1.2 Management of the Metabolic Syndrome 292

8.2 Obesity/Disorders of Energy 293

8.2.1 Disease State 293

8.2.2 Disease Basis 294

8.2.3 Current Treatment 294

8.2.4 Unmet Medical Needs 299

8.2.5 New Research Areas 302

8.3 Diabetes 308

8.3.1 Introduction 308

8.3.2 Disease Basis 309

8.3.3 Current Treatment 313

8.3.4 Unmet Medical Needs 327

8.3.5 New Research Areas 328

8.4 Problems 332

References 332

本章重点内容 333

Chapter 9 Agents for Gastrointestinal Diseases 335

9.1 Introduction 335

9.1.1 The Function of Gastrointestinal Tract 335

9.1.2 Historical Overview 335

9.2 Gastric and Mucosal Ulceration 338

9.2.1 Overview 338

9.2.2 Disease Basis 338

9.2.3 Current Treatment 339

9.2.4 Unmet Medical Needs 348

9.2.5 New Research Areas 349

9.3 Inflammatory Bowel Disease 349

9.3.1 Overview 349

9.3.2 Disease Basis 350

9.3.3 Current Treatment 351

9.3.4 Unmet Medical Needs 355

9.3.5 New research Areas 355

9.4 Emesis/Prokinetic Agents 358

9.4.1 Overview 358

9.4.2 Disease Basis 358

9.4.3　Current Treatment 360

9.4.4　Unmet Medical Needs 368

9.4.5　New research Areas 368

9.5　Problems 369

References 369

本章重点内容 370

Chapter 10　Cardiovascular Agents 372

10.1　Introduction 372

10.2　Hypertension 372

10.2.1　Disease Basis 372

10.2.2　Current Antihypertensive Agents 374

10.2.3　Unmet Medical Needs 396

10.2.4　New Research Areas 397

10.3　Cardiac Arrhythmias 397

10.3.1　Disease Basis 397

10.3.2　Current Anti-arrhythmic Agents 398

10.3.3　Unmet Medical Needs 406

10.3.4　New Research Areas 406

10.4　Congestive Heart Failure 407

10.4.1　Disease Basis 407

10.4.2　Current Cardiac Agents 407

10.5　Angina 411

10.5.1　Disease Basis 411

10.5.2　Current Anti-anginal Agents 411

10.6　Hyperlipidemias 413

10.6.1　Disease Basis 413

10.6.2　Anti-hyperlipidemic Agents 415

10.7　Problems 424

References 424

选读资料 425

本章重点内容 426

Chapter 11　Anticancer Agents 429

11.1　Introduction 429

11.2　Alkylating and Platinum Anticancer Agents 429

11.2.1　Current Treatments 430

11.2.2　Platinum Complexes 439

11.3　Deoxyribonucleic Acid Topoisomerase Inhibitors 441

11.3.1　Topoisomerase Ⅰ Inhibitors Camptothecin and Analogs 442

11.3.2　Topoisomerase Ⅱ Inhibitors 443

11.4 Antimetabolites 449

11.4.1 Current Treatment 449

11.5 Microtubule Targeting Agents 457

11.5.1 Inhibitors of Microtubule Assembly 458

11.5.2 Microtubule Stabilizers 460

11.6 Unmet Medical Needs and New Research Areas 462

11.6.1 Tyrosine Kinase and Inhibitors 463

11.6.2 Multi-targeted Kinase Inhibitors 465

11.6.3 Histone Deacetylase Inhibitors 466

11.6.4 Proteasome Inhibitors 467

11.6.5 Other New Research Areas 468

11.7 Problems 469

References 469

本章重点内容 470

Chapter 12 Antiviral 472

12.1 Antivirals for Herpesviruses 472

12.1.1 Introduction 472

12.1.2 Disease Basis 473

12.1.3 Current Treatment 473

12.1.4 Structure-activity Relationship 477

12.1.5 Unmet Medical Needs 480

12.1.6 New Research Areas 480

12.2 Antivirals for Human Immunodeficiency Virus 481

12.2.1 Introduction 481

12.2.2 Disease Basis 481

12.2.3 Current Treatment 482

12.2.4 Structure-activity Relationship 488

12.2.5 Unmet Medical Needs 492

12.2.6 New Research Areas 493

12.3 Antivirals for Influenza Virus 496

12.3.1 Introduction 496

12.3.2 Disease Basis 496

12.3.3 Current Treatment 497

12.3.4 Structure-activity Relationship 500

12.3.5 Unmet Medical Needs 504

12.3.6 New Research Areas 504

12.4 Problems 505

选读资料 505

本章重点内容 506

Chapter 13 Antifungal Agents 508

13.1 Introduction 508

13.1.1 General Classification and Structure of Medically Important Fungi 508

13.1.2 Human Pathogenic Fungi and Disease States 509

13.2 Current Antifungal Agents 511

13.2.1 General 511

13.2.2 The Mechanism of Action 512

13.3 Typical Antifungal Drugs in Clinical Use 513

13.3.1 Amphotericin B 513

13.3.2 Azoles 516

13.3.3 Allylamines 522

13.4 New Research Areas 525

13.4.1 Overview 525

13.4.2 Isoleucyl-tRNA Synthetase Inhibitors(ITRS) 525

13.4.3 Sphingolipid Biosynthesis Inhibitors 526

13.5 Problems 527

本章重点内容 528

Chapter 14 Antibacterials 529

14.1 Introduction 529

14.2 β-lactam 532

14.2.1 History and Overview 532

14.2.2 Mode of Action 534

14.2.3 Mechanisms of Resistance 537

14.2.4 Major Drug Classes 539

14.3 Macrolide 547

14.3.1 Introduction 547

14.3.2 Mechanism of Action 548

14.3.3 Major Classes of Macrolides 551

14.4 Tetracyclines 557

14.4.1 Introduction 557

14.4.2 SAR of Tetracyclines 558

14.4.3 Mechanism of Action 559

14.4.4 Major Classes of Tetracyclines 561

14.4.5 Antibacterial Resistance to the Tetracyclines 563

14.5 Quinolones 565

14.5.1 Overview of Quinolones 565

14.5.2 Mechanism of Antibacterial Action 567

14.5.3 SAR and STR of Quinolones 568

14.5.4 Antibacterial Resistance Mechanisms 568

14.5.5 Synthesis of Quinolones 568

14.6 Oxazolidinone 571

14.6.1 Introduction 571

14.6.2 SAR Leading to DuP-721 and DuP-105 572

14.6.3 SAR Leading to Eperezolid and Linezolid 572

14.6.4 Synthesis of Linezolid 574

14.6.5 Mode of Action 575

14.7 Aminoglycosides,glycopeptides,and others 575

14.7.1 Vancomycin 575

14.7.2 Aminoglycosides 576

14.7.3 Dapotamycin 578

14.8 Antimycobacterium Agents 579

14.8.1 Introduction 579

14.8.2 Rifamycin 581

14.8.3 Isoniazid 581

14.9 Resistance and Challenge[3] 583

14.10 Problems 585

References 585

本章重点内容 586

Chapter 15 Antiparasitics 589

15.1 Introduction 589

15.2 Representative Diseases 590

15.2.1 African Trypanosomiasis 590

15.2.2 Chagas disease 591

15.2.3 Leishmaniasis 592

15.2.4 Malaria 593

15.3 Antimalarias 594

15.3.1 Quinolines 596

15.3.2 Artemisinin and its analogs 600

15.4 Problems 604

References 605

本章重点内容 606

Chapter 16 Inflammatory Diseases and Nonsteroidal Anti-inflammatory Drugs(NSAIDs) 608

16.1 Introduction 608

16.1.1 Arthritis 609

16.1.2 Other Inflammatory and Immunological Diseases 612

16.2 Disease Basis 614

16.2.1 Arachidonic Acid Cascade 614

16.2.2 Phospholipase A2(PLA2) 616

16.2.3 Cyclooxygenase(COX) 618

16.2.4 Lipoxygenase(LOX) 619

16.3 Current Treatment for Arthritis 620

16.3.1 Steroids(Brief Introduction) 620

16.3.2 Nonsteroidal Anti-inflammatory Drugs(NSAIDs) 622

16.4 New Research Areas 644

16.4.1 Disease-modifying Anti-rheumatic Drugs 644

16.4.2 Structure-modifying Anti-inflammatory Drugs 645

16.5 Conclusions and Future Directions 648

16.6 Problems 649

References 649

本章重点内容 651

索引 653