1st Edition

SAR Side Effects and Drug Design

By Eric J. Lien Copyright 1987

    SAR focuses on the quantitative structure-activity relationship (QSAR) of the disposition and activities of various pharmacological groups – the first systematic approach for linking different side effects of drugs to their molecular structure and physiochemical properties.


    This unique monograph describes the application of molecular modification to the practical improvement of therapeutic agents; depicts the quantitative measurement of biological activity as it relates to QSAR; provides essential guidance on selecting suitable mathematical models, defining appropriate parameters in correlation studies and anticipating potential side effects during the tedious drug development process.

    About the Series -- Preface -- 1. Theories of Drug Action -- I. Evolution of Concepts of Drug-Receptor Interaction -- II. Occupancy Theory -- III. Rate Theory -- IV. Induced-Fit Theory: Allosteric Site and Cooperative Effect -- V. Macromolecular Perturbation Theory -- VI. The Second Messenger Concept -- VII. Active-Site-Directed Irreversible Inhibitors -- VIII. Mechanism- and Pharmacophore-Based Drug Design -- References -- 2. Improvement of Therapeutic Agents by Molecular Modification -- I. Modification of the Absorption of Drugs -- II. Optimization of Time Course and Distribution by Chemical Modification -- III. Modification of the Intrinsic Pharmacological Activity -- IV. Minimization of Biodegradation of Drugs -- V. Improvement of Acceptability by Chemical Modification -- References -- 3. Quantitative Structure-Activity Relationship -- I. Dose-Response Curve and Quantitative Measurement of Biological Activity -- II. Kinetics Versus Thermodynamics -- III. Structure-Acidity-Solubility Relationship -- IV. Multiple Regression Analysis and Numerical Presentation of Physicochemical Parameters -- V. QSAR of Convulsants, Anticonvulsants, and Depressants -- VI. QSAR of Narcotic Analgetics -- VII. QSAR of Antihistamines and Anticholinergics -- VIII. QSAR of Stereoisomers -- References -- 4. Ribonucleotide Reductase Inhibitors as Antiviral and Anticancer Agents -- I. Ribonucleotide Reductase (Ribonucleoside Diphosphate Reductase) as a Biochemical Target -- II. Inhibitors of RR -- References -- 5. Chemical Structure and Side Effects -- I. Extrapyramidal Syndrome -- II. Bone Marrow Depression and Blood Dyscrasias -- III. Hepatotoxicity -- IV. Nephrotoxicity -- V. Ototoxicity -- VI. Skin Sensitization and Drug-Induced Eosinophilia 281 VII. Glaucoma and Cataracts -- VIII. Carcinogenicity of Anticancer Drugs -- References -- Appendix -- Index.


    Eric J. Lien is Professor of Pharmacy and Biomedical Chemistry at the University of Southern California School of Pharmacy, Los Angeles. Dr. Lien is the author of SAR Analysis and Anticancer Chinese Drugs and Related Plants and U.S. New Drug Digest, 1980-86, as well as over 160 scientific papers and chapters in pharmaceutical textbooks. He is on the editorial boards of Journal of Clinical and Hospital Pharmacy and Oriental Healing Arts International Bulletin. A member of many scientific and professional societies, Dr. Lien also serves as a consultant to the National Institutes of Health. He received the B.S. (1960) degree in pharmacy from the School of Pharmacy, College of Medicine, National Taiwan University, Ph.D. (1966) degree in pharmaceutical chemistry from the University of California, San Francisco Medical Center, and did postdoctoral work (1968) at Pomona College, Claremont, California.