Medicinal Chemistry Advances (eBook)

Proceedings of the Seventh International Symposium on Medicinal Chemistry, Torremolinos, Spain 2 - 5 September 1980

Federico G. De Las Heras, Salvador Vega (Herausgeber)

eBook Download: PDF

2016 | 1. Auflage
526 Seiten
Elsevier Science (Verlag)
978-1-4831-5821-1 (ISBN)

Infos

Medicinal Chemistry Advances covers the proceedings of the Seventh International Symposium on Medicinal Chemistry. The book reviews the papers presented in the symposium.
The main topics that this book covers are nucleosides in chemotherapy; theoretical approaches to medicinal chemistry; platelets and antithrombotic agents; receptors; antiviral agents; antilipidemic agents; respiratory system; central nervous system; enzyme inhibitors; and bioactive peptides.
Chemists, pharmacologists, biochemists, physicians and other professionals and researchers concerned with the development of pharmaceutical field will find this book interesting.

Inhalt

Front Cover 1
Medicinal Chemistry Advances 4
Copyright Page 5
Contents 6
List of Contributors 10
Introduction 14
Chapter 1. Current Options in Drug Design 16
ABSTRACT 16
KEYWORDS 16
INTRODUCTION 16
THE DISCOVERY OF "LEAD" COMPOUNDS 17
DRUGS AT RECEPTOR SITES 19
MOLECULAR MODIFICATION 21
REFERENCES 24
Chapter 2. Medicinal Chemistry and Current Problems in Drug Development 26
ABSTRACT 26
KEY WORDS 26
INTRODUCTION 26
ACKNOWLEDGMENT 41
Chapter 3. 2'-Fluoro-arabinosyl Pyrimidine Nucleosides: Chemistry, Antiviral, and Potential Anticancer Activities 42
ABSTRACT 42
KEYWORDS 42
REFERENCES 54
Chapter 4. Nucleoside Antibiotics. Mode of Action 56
ABSTRACT 56
KEYWORDS 56
INTRODUCTION 56
INHIBITORS OF NUCLEIC ACID SYNTHESIS 59
INHIBITORS OF PROTEIN SYNTHESIS 59
REFERENCES 67
Chapter 5. Antitumor and Antiviral Activity of N6-Hydroxyadenine Nucleosides and Related Derivatives 70
ABSTRACT 70
KEYWORDS 70
INTRODUCTION 70
RIBOSYL NUCLEOSIDES 72
ARABINOSYL DERIVATIVES 74
2-SUBSTITUTED PURINE NUCLEOSIDES 77
DISCUSSION AND CONCLUSIONS 80
ACKNOWLEDGEMENTS 81
REFERENCES 81
Chapter 6. Alkylating Nucleosides 84
ABSTRACT 84
KEYWORDS 84
INTRODUCTION 84
CHEMISTRY 86
CYTOSTATIC ACTIVITY 92
MODE OF ACTION 96
ACKNOWLEDGMENTS 97
REFERENCES 97
Chapter 7. Molecular Engineering: A General Approach to QSAR 100
ABSTRACT 100
KEYWORDS 100
INTRODUCTION 100
MOLECULAR SPACES 102
PARAMETERS 104
MOLECULAR ENGINEERING 106
METHODOLOGICAL TOOLS 106
PATTERN RECOGNITION 108
THE FUTURE OF QSAR 109
REFERENCES 110
Chapter 8. Towards More Realistic Computer Simulations in Theoretical Molecular Biology 112
Electrostatic Potential Maps Versus Iso-energy Maps 112
Characterization of an Atom in a Molecule 112
Basis Set Superposition Error 113
Direct Computations of the Correlation Energy Correction 113
Indirect Computations of the Inter-molecular Correlation Energy Correction 113
Induction Energy Correction 114
Static Reaction Field 114
Temperature Induced Degeneracy 114
Entropy and Free Energy Computations 115
Time Dependent Simulations 115
REFERENCES 116
Chapter 9. AB Initio Quantum Chemical Approach to the Antibiotic Activity of ß-Lactams 118
ABSTRACT 118
KEYWORDS 118
INTRODUCTION 118
PROCEDURE 119
REACTION SURFACES 120
ANALYSIS OF THE MOLECULAR ORBITALS AND ATOMIC CHARGES 127
CONCLUSIONS 129
ACKNOWLEDGEMENTS 130
REFERENCES 130
Chapter 10. Cyclic Analogues of Agonists as a Tool for Structure-Activity Relationships 132
ABSTRACT 132
KEYWORDS 132
INTRODUCTION 132
METHODS OF CONTROLLING MOLECULAR GEOMETRY 133
CYCLIC ACETYLCHOLINE ANALOGUES 134
CYCLIC FENTANYL ANALOGUES 140
CYCLIC SEROTONIN ANALOGUES 141
ACKNOWLEDGEMENT 143
REFERENCES 143
Chapter 11. Thromboxane A2 and Atherosclerosis 146
ABSTRACT 146
KEYWORDS 146
INTRODUCTION 146
VASCULAR INJURY AND ATHEROGENICITY 147
ENDOTHELIOPATHY 147
THROMBOXANE A2 IN VASCULAR INJURY 147
THROMBOXANE A2 IN THROMBUS FORMATION 149
PLASMA THROMBOXANE B2 LEVELS 150
PHTHALAZINOL 152
CONCLUDING REMARKS 153
ACKNOWLEDGEMENT 154
REFERENCES 154
Chapter 12. Biological Activities of Some Metabolites and Analogues of Prostacyclin 156
ABSTRACT 156
KEYWORDS 156
INTRODUCTION 156
ACTIVITY OF PROSTACYCLIN METABOLITES 160
ACTIVITY OF STABLE PROSTACYCLIN ANALOGUES 165
REFERENCES 171
Chapter 13. The Role of Platelet Inhibitors in Degenerative Vascular Diseases 174
MODE OF ACTION OF ANTIHYPERTENSIVES 176
REFERENCES 179
Chapter 14. Thromboxane-Dependent Platelet Aggregation: Role and Limitations 180
ABSTRACT 180
KEYWORDS 180
INTRODUCTION 180
I. THREE PATHWAYS FOR PLATELET AGGREGATION 181
II. PLATELET-ACTIVATING FACTOR (PAF-ACETHER) 181
III. RELEASE OF PAF-ACETHER BY PLATELETS 181
IV. THIRD PATHWAY AND PAF-ACETHER 182
V. PHARMACOLOGICAL CONTROL OF FORMATION OF PAF-ACETHER BY PLATELETS 182
CONCLUSION 182
REFERENCES 183
Chapter 15. Pharmacological and Biochemical Studies on Benzodiazepines 186
ABSTRACT 186
KEYWORDS 186
INTRODUCTION 186
RELATIONSHIP BETWEEN ANTILEPTAZOL ACTIVITY AND BRAIN CONCENTRATIONS OF BENZODIAZEPINES 186
IMPORTANCE OF METABOLITES IN THE ACTION OF BENZODIAZEPINES 188
RELATIONSHIP BETWEEN BENZODIAZEPINE BRAIN LEVELS AND HIGH AFFINITY DRUG BINDING SITES 190
CONCLUSIONS 191
REFERENCES 192
Chapter 16. Receptor Mapping 194
ABSTRACT 194
KEYWORDS 194
ACKNOWLEDGMENTS 205
REFERENCES 205
Chapter 17. Multiple Analgesic Receptors 206
ABSTRACT 206
KEYWORDS 206
I. New insights on the drug-receptor interaction 207
II. Opiate-Receptors 208
III. Mechanisms of analgesia 211
IV. Clinical and therapeutic relevance of opiate receptor research 215
REFERENCES 220
Chapter 18. New Approaches to Antiviral Agents 226
ABSTRACT 226
KEYWORDS 226
INTRODUCTION 226
VIRUSES PERMEABILIZE CELLS DURING INFECTION 227
INHIBITORS IMPERMEABLE TO NORMAL CELLS AS SELECTIVE ANTIVIRAL AGENTS 228
PROTEIN TOXINS CAN PENETRATE INTO VIRUS- INFECTED CELLS 231
THE MODIFICATION OF MEMBRANE PERMEABILITY BY ANIMAL VIRUSES AND IONOPHORES IS SIMILAR 233
ANTIVIRAL PROPERTIES OF INTERFERON 233
CONCLUDING REMARKS 237
ACKNOWLEDGEMENTS 238
REFERENCES 238
Chapter 19. New Antiviral Agents: Some Recent Developments 240
ABSTRACT 240
KEYWORDS 240
INTRODUCTION 240
FACTORS IN DEVELOPMENT OP ANTIVIRAL AGENTS 240
ADAMANTANE ANALOGUES 241
RIBAVIRIN 242
BENZIMIDAZOLE ANALOGUES 243
PHOSPHCWOACETATE (PAA) AND PHOSPHONQPORMATE (PFA) 243
ACYCLIC B-DIKETONES 244
GLUCOSE ANALOGUES AND GLUCOSIDES 245
PRODUCTS OP NATURAL ORIGIN 250
VIRAL ENZYME INHIBITORS 251
ACKNOWLEDGEMENTS 251
REFERENCES 251
Chapter 20. Chemical Control of Oncogenic Events by RNA Tumor Viruses 254
ABSTRACT 254
1. INTRODUCTION 255
2. APPROACHES TO INHIBITING ONCOGENESIS BY RNA TUMOR VIRUSES 256
3. CLASSIFICATION OF INHIBITORS 258
4. EFFECT OF 5-ALKYL-2 '-DEOXYURI DINE 5 '- TRIPHOSPHATES ON THE DNA-POLYMERIZING ENZYME ACTIVITIES. 259
5. ANTITEMPLATE APPROACH TO DEVELOP SELECTIVE INHIBITORS OF DNA SYNTHESIS 263
6. FUTURE PROSPECTS 270
ACKNOWLEDGMENTS 271
REFERENCES 271
Chapter 21. General Mechanisms of Action of Hypolipidemic Agents 274
ABSTRACT 274
KEYWORDS 274
INTRODUCTION 274
GENERAL MECHANISMS OF ACTION OF HYPOLIPIDEMIC DRUGS 276
THE HYPOLIPIDEMIC EFFECT OF GLUCAGON 281
NEW APPROACHES TO HYPOLIPIDEMIC AGENTS 282
REFERENCES 283
Chapter 22. Central Mechanisms of Anorectic Drugs 286
ABSTRACT 286
KEYWORDS 286
INTRODUCTION 286
DOPAMINE 287
NORADRENALINE 290
SEROTONIN 292
CONCLUSIONS 294
REFERENCES 294
Chapter 23. Antiobesity Agents Acting Through Peripheral Mechanisms 298
ABSTRACT 298
KEYWORDS 298
INTRODUCTION 299
ANORECTIC AGENTS WHICH FUNCTION AT PERIPHERAL SITES 299
PERIPHERAL EFFECTS OF AN0RECTIC AGENTS WHICH FUNCTION AT BRAIN SITES 301
AGENTS WHICH REDUCE THE AVAILABILITY OF NUTRIENTS THROUGH MODULATION OF INTESTINAL ABSORPTION 301
INHIBITORS OF LIPID SYNTHESIS 304
AGENTS WHICH DECREASE THE EFFICIENCY OF LIPID AND/OR CARBOHYDRATE OXIDATION 306
AGENTS WHICH ENHANCE LIPID MOBILIZATION 307
AGENTS WHICH NORMALIZE HORMONE LEVELS 307
ACKNOWLEDGEMENT 308
REFERENCES 308
Chapter 24. Agents Acting on Mucociliary System 314
ABSTRACT 314
KEYWORDS 314
INTRODUCTION 314
PHARMACOLOGICAL DEFINITIONS 316
AGENTS ACTING ON MUCOCILIARY SYSTEM 317
ASSAY METHODS 324
RESULTS 326
CONCUSION 327
REFERENCES 327
Chapter 25. Adrenergic and Anticholinergic Bronchodilators Do They Act as Bronchospasmolytics? Perspectives in the development of anti-asthmatics
ABSTRACT 332
KEYWORDS 332
ANTI-ASTHMATIC AGENTS 332
BRONCHIAL OBSTRUCTION PROVOCATING AGENTS 333
BRONCHIAL OBSTRUCTING AND BRONCHODILATING AGENTS: LOCATION OF THEIR SITES OF ACTION 333
REVISION OF THE CLASSICAL CONCEPT ON THE MECHANISM OF ACTION OF BRONCHIAL SMOOTH MUSCLE SPASMOGENS AND SPASMOLYTICS 335
ß–ADRENERGIC RECEPTORS IN BRONCHIAL ASTHMA 337
ß– AND a–ADRENERGIC RECEPTORS IN BRONCHIAL ASTHMA 339
CHOLINERGIC RECEPTORS IN BRONCHIAL ASTHMA 339
LOCAL ANESTHETICS AND BRONCHODILATION 341
REFERENCES 342
Chapter 26. Agents Acting on the Immunological Component in Respiratory Diseases 344
ABSTRACT 344
KEYWORDS 344
INTRODUCTION 344
HISTORICAL DEVELOPMENT OF INHIBITORS OF MEDIATOR RELEASE 344
CHROMONES 346
QUINOLONES 347
XANTHONES, THIOXANTHONES AND ANALOGS 348
OXAMATES 349
MISCELLANEOUS 351
SRS-A ANTAGONISTS 352
ANTIHISTAMINES 353
ANTHRANILIC ACIDS 353
SYNTHESIS AND DEVELOPMENT OF ADAMANTYLCARBOXAMIDOPHENYLACETIC ACIDS AS POTENTIAL ANTIALLERGY DRUGS 354
HISTORICAL 354
CHEMISTRY 354
BIOLOGY 355
CONCLUSION 356
REFERENCES 356
Chapter 27. Present Knowledge of GABA Receptor Agonists 360
ABSTRACT 360
KEYWORDS 360
1. INTRODUCTION 360
2. GABA-TRANSAMINASE INHIBITORS - GABA RECEPTOR AGONISTS 361
3. ACTIONS AND SITES OF ACTIONS OF GABA RECEPTOR AGONISTS IN THE CENTRAL NERVOUS SYSTEM 362
4. THERAPEUTICAL IMPLICATIONS 365
REFERENCES 367
Chapter 28. New Trends in Minor Tranquilizers 370
ABSTRACT 370
KEYWORDS 370
INTRODUCTION 370
1,4-BENZODIAZEPINES AND SIMILAR STRUCTURES 371
Pharmacology 372
Other Biological Activities 374
Chemical Variations 374
Related Structures 376
Mechanism of Action 376
Other Structures 380
CONCLUSIONS 381
ACKNOWLEDGEMENT 381
REFERENCES 381
Chapter 29. Trans-N-Alkyl- 6, 7-Dihydroxyoctahydrobenzo[g]- Quinolines: Apomorphine Congeners Lacking the Non-Oxygenated Aromatic Ring 384
ABSTRACT 384
KEYWORDS 384
INTRODUCTION 384
CHEMISTRY 386
PHARMACOLOGY 389
STRUCTURE-ACTIVITY CONSIDERATIONS 391
ACKNOWLEDGEMENT 395
REFERENCES 395
Chapter 30. Dopamine Receptor Blockade by Substitute Benzamide Drugs 398
ABSTRACT 398
KEYWORDS 398
INTRODUCTION 398
DOPAMINERGIC MECHANISMS 399
SUBSTITUTED BENZAMIDES AS DOPAMINE RECEPTOR BLOCKING AGENTS 404
REFERENCES 410
Chapter 31. Target Enzyme-Activated Irreversible Enzyme Inhibitors 412
ABSTRACT 412
KEYWORDS 412
INTRODUCTION 412
INHIBITORS OF 4-AMINOBUTYRATE:2-OXOGLUTARATE AMINOTRANSFERASE (GABA-T) 413
INHIBITORS OF ORNITHINE DECARBOXYLASE (ODC) 416
Ornithine decarboxylase 417
Proposed inhibition by a-acetylenic putrescine 417
APPROACHES TO THE INHIBITION OF STEROID 5-a-REDUCTASE 419
PERSPECTIVE 422
ACKNOWLEDGMENTS 423
REFERENCES 423
Chapter 32. Proteolytic Enzyme Inhibitors 426
ABSTRACT 426
KEYWORDS 426
INTRODUCTION 426
MICROBIAL INHIBITORS 427
PLASMA a2-MACROGLOBULIN 429
PLASMA INHIBITORS 430
PROTEIN PROTEINASE INHIBITORS OF LOW MOLECULAR WEIGHT 431
INHIBITORS REACTING BY DISULFIDE - INTERCHANGE 433
PROTEINASE INHIBITOR AS DRUGS 434
ACKNOWLEDGEMENT 435
REFERENCES 435
Chapter 33. Sialidases and Their Inhibitors 438
ABSTRACT 438
KEYWORDS 438
SIALIDASES AND THEIR INHIBITORS 438
Biological Functions 446
ACKNOWLEDGEMENT 447
REFERENCES 448
Chapter 34. Inhibitors of Cyclic Nucleotide Phosphodiesterases 450
ABSTRACT 450
KEYWORDS 450
INTRODUCTION 450
CYCLIC NUCLEOTIDE PHOSPHODIESTERASES 451
COMPETITIVE PHOSPHODIESTERASE INHIBITORS 452
CALMODULIN INHIBITORS 455
PHARMACOLOGICAL PROPERTIES OF PHOSPHODIESTERASE INHIBITORS 456
THERAPEUTIC PERSPECTIVES AND CONCLUSION 456
ACKNOWLEDGEMENT 458
REFERENCES 458
Chapter 35. The Systematics of Bioactive Peptide Structure-Activity Relationships 462
ABSTRACT 462
KEYWORDS 462
INTRODUCTION 462
CONTRACTION OF CHAIN 464
EXTENSION OF CHAIN 466
MODIFICATION OF SIDE CHAINS 467
D-SUBSTITUTION 468
a-AZA-SUBSTITUTION 471
CARBA SUBSTITUTION 472
OTHER BACKBONE MODIFICATIONS 472
CONCLUSION 473
REFERENCES 473
Chapter 36. Chemical and Biological Properties of Beta-Lipotropin and Endorphins: Metabolism and Mechanisms of Inactivation 476
ABSTRACT 476
KEYWORDS 476
INTRODUCTION 476
BIOSYNTHESIS 478
RELEASE AND MODE OF ACTION 479
METABOLISM AND INACTIVATION 480
SYNTHETIC ANALOGUES 482
CONCLUSION 483
ACKNOWLEDGEMENT 484
REFERENCES 484
Chapter 37. Neurohypophysial Hormones and Neurophysins: Structures, Precursors and Evolution 488
ABSTRACT 488
KEYWORDS 489
INTRODUCTION 489
NEUROHYPOPHYSIAL HORMONES 490
NEURQPHYSINS 493
OOMMDN PRECURSORS 497
REIERENCES 499
Chapter 38. Relations Between the Structure and Biological Activity of Insulin 502
ABSTRACT 502
KEYWORDS 502
INTRODUCTION 502
PREPARATION OF INSULIN ANALOGUES AND DERIVATIVES 503
EFFECT OF MODIFICATIONS ON THE PROPERTIES OF INSULIN 509
ACKNOWLEDGEMENT 515
REFERENCES 515
Index 518

Produkt-Details

• Erscheint lt. Verlag: 20.4.2016
• Sprache: englisch
• Themenwelt: Medizin / Pharmazie ► Gesundheitsfachberufe
• Themenwelt: Medizin / Pharmazie ► Medizinische Fachgebiete ► Pharmakologie / Pharmakotherapie
• Themenwelt: Naturwissenschaften ► Chemie
• Themenwelt: Technik
• ISBN-10: 1-4831-5821-7 / 1483158217
• ISBN-13: 978-1-4831-5821-1 / 9781483158211