FOYE'S

Principles of
Medicinal
Chemistry
SIXTH EDITION

Edited By Assistant Editors

THOMAS L LEMKE, P H D
Professor Emeritus
College of Pharmacy
University of Houston
Houston, Texas
DAVID A. WILLIAMS, P H D
Professor Emeritus of Chemistry
Massachusetts College of Pharmacy and
Health Sciences
Boston, Massachusetts
VICTORIA F. ROCHE, P H D
Senior Associate Dean
School of Pharmacy and Health Professions
Creighton University
Omaha, Nebraska
S. WILLIAM ZITO, P H D
Professor of Pharmaceutical Sciences
College of Pharmacy and
Allied Health Professions
St. John's University
Jamaica, Neiv York

© . Wolters Kluwer Lippincott Williams & Wilkins

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 CONTENTS

Historical Perspective of Medicinal Chemistry 1 Chapter 14 Serotonin Receptors and Drugs Affecting
JOHN L NEUMEYER Serotonergic Neurotransmission 417
RICHARD A. GLENNON AND MALGORZATA
PART I: PRINCIPLES OF DRUG DISCOVERY DUKAT-GLENNON
Chapter 1 Drug Discover)' from Natural Products 12 Chapter 15 Amino Acid Neurotransmitters in the
A. DOUGLAS KINGHORN Central Nervous System 444
Chapter 2 Drug Design and Relationship of TIMOTHYJ. MAHER
Functional Groups to Pharmacologic Chapter 16 Inhibitors of Nerve Conduction: Local
Activity 26 Anesthetics 462
JAMESJ. KNITTEL AND ROBIN M. ZAVOD MATTHIAS C. LU
Chapter 3 Molecular Modeling and In Silico Drug Chapter 17 Phosphodiesterase Inhibitors 480
Design 54 KEVIN DALBY
XIANG-QUN (SEAN) XIE PART III: PHARMACODYNAMIC AGENTS
Chapter 4 Receptors and Drug Action 85 Section 1: Drugs Affecting Central Nervous System
TIMOTHY A. MAHER AND DAVID A. JOHNSON Chapter 18 General Anesthetics 490
Chapter 5 Drug Discovery Through Enzyme TIMOTHYJ. MAHER
Inhibition 99 Chapter 19 Sedative-Hypnotics 504
STEPHEN KERR WILLIAM SOINE
Chapter 6 Pharmaceutical Biotechnology— Chapter 20 Antiseizure Agents 521
From Nucleic Acids to Personalized BARBARA LEDUC
Medicine 115
Chapter 21 Antidepressants 547
RONALD E. REID AND ROBERT D. SINDELAR
DAVID A. WILLIAMS
Chapter 7 Peptide and Protein Drugs 175
Chapter 22 Psychotherapeutic Drugs: Antipsychotic
MICHAEL MOKOTOFF
and Anxiolytic Agents 601
Chapter 8 Antisense Therapeutic Agents 201 RAYMOND G. BOOTH
MARILYN SPEEDIE
Chapter 23 Hallucinogens, Stimulants and Related
Chapter 9 Physicochemical and Biopharmaceutical Drugs of Abuse 631
Properties of Drug Substances and RICHARD A. GLENNON
Pharmacokinetics 210 Chapter 24 Opioid Analgesics 652
SUNILS.JAMBHEKAR
DAVIDS. FRIES
Chapter 10 Drug Metabolism 253 Chapter 25 Drugs Used to Treat Neuromuscular
DAVID A. WILLIAMS
Disorders: Antiparkinsonian and
Chapter 11 U. S. Drug Regulation: An Overview 327 Spasmolytic Agents 679
DOUGLASJ. PISANO RAYMOND G. BOOTH

PART II: DRUG RECEPTORS AFFECTING Section 2: Drugs Affecting the Cardiovascular System
NEUROTRANSMISSION AND ENZYMES AS Chapter 26 Cardiac Agents: Cardiac Glycosides,
CATALYTIC RECEPTORS Antianginal, and Antiarrhythmic
Overview of Drug Receptors: A Perspective 340 Drugs l 698
DAVIDJ.TRIGGLE AHMED S. MEHANNA
Chapter 12 Drugs Affecting Cholinergic Chapter 27 Diuretics 722
Neurotransmission 361 GARYO. RANKIN
E. KIM FIFER Chapter 28 Angiotensin-Converting Enzyme
Chapter 13 Adrenergic Receptors and Drugs Affecting Inhibitors, Antagonists and Calcium
Adrenergic Neurotransmission 392 Blockers 738
ROBERT K. GRIFFITH MARC HARROLD
XIV CONTENTS

Chapter 29 Central and Peripheral Sympatholytics Section 5: Chemotherapeutic Agents

and Vasodilators 769 Chapter 38 Antibiotics and Antimicrobial Agents 1028
DAVID A. WILLIAMS LESTER A. MITSCHER, THOMAS L LEMKE,
Chapter 30 Antihyperlipoproteinemics and Inhibitors AND ELMERJ. GENTRY
of Cholesterol Biosynthesis 797 Chapter 39 Antiparasitic Agents 1084
MARC HARROLD THOMAS L LEMKE
Chapter 31 Antithrombotics, Thrombolytics, Chapter 40 Antifungal Agents 1112
Coagulants, and Plasma Extenders 820 ROBERT K. GRIFFITH
MATTHIAS C. LU AND THOMAS L LEMKE
Chapter 41 Antimycobacterial Agents 1127
THOMAS L LEMKE
Section 3: Drugs Affecting the Hormonal Systems Chapter 42 Cancer and Chemotherapy 1147
Chapter 32 Insulin and Drugs Used for the Treatment VICTORIA F. ROCHE
of Diabetes 855 Chapter 43 Antiviral Agents and Protease
ROBIN M. ZAVODJOHN L. KRSTENANSKY, Inhibitors 1193
AND BRUCE L. CURRIE PATRICK M. WOSTER
Chapter 33 Adrenocorticoids 877
DUANE D. MILLER, ROBERTW. PART IV: DISEASE STATE MANAGEMENT
BRUEGGEMEIER AND JAMES T. DALTON Chapter 44 Asthma and Chronic Obstructive
Chapter 34 Thyroid Function and Thyroid Drugs 913 Pulmonary Disease 1230
ALI R. BANIJAMALI S. WILLIAM ZITO
Chapter 35 Calcium Homeostasis 935 Chapter 45 Men's Health 1265
ROBIN M. ZAVOD DUANE D. MILLER, ROBERTW.
BRUEGGEMEIER, AND JAMES T. DALTON

Section 4: Drugs Affecting the Immune Systems Chapter 46 Women's Health 1301
ROBIN M. ZAVOD
Chapter 36 Nonsteroidal Anti-Inflammatory
Appendix A: pKa Values for Some Drugs and
Drugs 954
RONALD BORNE, MARK LEVI, NORMAN Miscellaneous Organic Acids and
WILSON Bases 1343
Appendix B: pH Values for Tissue Fluids 1354
Chapter 37 Antihistamines and Related Antiallergic
and Antiulcer Agents 1004 Drug Index 1355
WENDELLNELSON Subject Index 1361