SAR side effects and drug design

Cover......Page 1
Half Title......Page 2
Series Page......Page 3
Title Page......Page 4
Copyright Page......Page 5
Dedication Page......Page 6
About the Series......Page 8
Preface......Page 10
Contents......Page 12
1. Theories of Drug Action......Page 16
 I. Evolution of Concepts of Drug-Receptor Interaction......Page 18
 II. Occupancy Theory......Page 21
 III. Rate Theory......Page 22
 IV. Induced-Fit Theory: Allosteric Site and Cooperative Effect......Page 23
 V. Macromolecular Perturbation Theory......Page 25
 VI. The Second Messenger Concept......Page 26
 VII. Active-Site-Directed Irreversible Inhibitors......Page 28
 VIII. Mechanism- and Pharmacophore-Based Drug Design......Page 30
 References......Page 35
 I. Modification of the Absorption of Drugs......Page 40
 II. Optimization of Time Course and Distribution by Chemical Modification......Page 42
 III. Modification of the Intrinsic Pharmacological Activity......Page 45
 IV. Minimization of Biodegradation of Drugs......Page 49
 V. Improvement of Acceptability by Chemical Modification......Page 51
 References......Page 53
3. Quantitative Structure-Activity Relationship......Page 56
 I. Dose-Response Curve and Quantitative Measurement of Biological Activity......Page 57
 II. Kinetics Versus Thermodynamics......Page 66
 III. Structure-Acidity-Solubility Relationship......Page 74
 IV. Multiple Regression Analysis and Numerical Presentation of Physicochemical Parameters......Page 107
 V. QSAR of Convulsants, Anticonvulsants, and Depressants......Page 117
 VI. QSAR of Narcotic Analgetics......Page 124
 VII. QSAR of Antihistamines and Anticholinergics......Page 140
 VIII. QSAR of Stereoisomers......Page 150
 References......Page 169
 I. Ribonucleotide Reductase (Ribonucleoside Diphosphate Reductase) as a Biochemical Target......Page 178
 II. Inhibitors of RR......Page 185
 References......Page 194
5. Chemical Structure and Side Effects......Page 198
 I. Extrapyramidal Syndrome......Page 203
 II. Bone Marrow Depression and Blood Dyscrasias......Page 207
 III. Hepatotoxicity......Page 224
 IV. Nephrotoxicity......Page 252
 V. Ototoxicity......Page 282
 VI. Skin Sensitization and Drug-Induced Eosinophilia......Page 296
 VII. Glaucoma and Cataracts......Page 306
 VIII. Carcinogenicity of Anticancer Drugs......Page 321
 References......Page 331
Appendix......Page 346
Index......Page 376