Wilson & Gisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry

by Block, John; Beale, John M.

• ISBN13: 9780781734813
• ISBN10: 0781734819
• Edition: 11th
• Format: Hardcover
• Copyright: 2003-12-16
• Publisher: LWW

Summary

For over half a century, this book has served the discipline of medicinal chemistry for both graduate and undergraduate pharmacy and chemistry students as well as practicing pharmacists. Fully updated for the Eleventh Edition, coverage begins with the fundamental principles of chemistry, biochemistry, and biology that underlie the discipline of medicinal chemistry. These principles are then applied to understanding the properties, mode of action, therapeutic applications, and limitations of various pharmaceutical agents. The subject matter is organized by pharmaceutical and therapeutic classes, providing a bridge between the basic sciences and clinical practice. The text contains many tables for quick reference to names, formulations, dosages, and applications.

Table of Contents

Preface	vii
Contributors	ix
Introduction	1	(2)
John H. Block
John M. Beale, Jr.
Physicochemical Properties in Relation to Biological Action	3	(40)
John H. Block
Overview	3	(1)
Drug Distribution	3	(6)
Acid-Base Properties	9	(8)
Statistical Prediction of Pharmacological Activity	17	(9)
Combinatorial Chemistry	26	(1)
Molecular Modeling (Computer-Aided Drug Design)	27	(14)
Selected Web Pages	41	(2)
Combinatorial Chemistry	43	(22)
Douglas R. Henry
How It Began: Peptides and Other Linear Structures	43	(3)
Drug-Like Molecules	46	(2)
Supports and Linkers	48	(1)
Solution-Phase Combinatorial Chemistry	49	(1)
Pooling Strategies	50	(1)
Detection, Purification, and Analysis	51	(1)
Encoding Combinatorial Libraries	52	(1)
High-Throughput Screening (HTS)	53	(1)
Virtual (in Silico) Screening	54	(1)
Chemical Diversity and Library Design	55	(3)
Report Card on Combinatorial Chemistry: Has It Worked?	58	(2)
Resources for Combinatorial Chemistry	60	(1)
Combinatorial Chemistry Terminology	60	(5)
Metabolic Changes of Drugs and Related Organic Compounds	65	(77)
Stephen J. Cutler
John H. Block
General Pathways of Drug Metabolism	65	(1)
Sites of Drug Biotransformation	66	(1)
Role of Cytochrome P-450 Monooxygenases in Oxidative Biotransformations	67	(2)
Oxidative Reactions	69	(34)
Reductive Reactions	103	(6)
Hydrolytic Reactions	109	(2)
Phase II or Conjugation Reactions	111	(15)
Factors Affecting Drug Metabolism	126	(16)
Prodrugs and Drug Latentiation	142	(18)
Forrest T. Smith
C. Randall Clark
History	142	(1)
Basic Concepts	142	(2)
Prodrugs of Functional Groups	144	(8)
Bioprecursor Prodrugs	152	(3)
Chemical Delivery Systems	155	(5)
Biotechnology and Drug Discovery	160	(37)
John M. Beale, Jr.
Biotechnology: An Overview	160	(1)
Biotechnology and Pharmaceutical Care	160	(1)
Literature of Biotechnology	160	(1)
Biotechnology and New Drug Development	160	(2)
The Biotechnology of Recombinant DNA (rDNA)	162	(4)
Some Types of Cloning	166	(1)
Expression of Cloned DNA	167	(1)
Manipulation of DNA Sequence Information	168	(1)
New Biological Targets for Drug Development	169	(1)
Novel Drug-Screening Strategies	170	(2)
Processing of the Recombinant Protein	172	(1)
Pharmaceutics of Recombinant DNA (rDNA)-Produced Agents	173	(2)
Delivery and Pharmacokinetics of Biotechnology Products	175	(1)
Recombinant Drug Products	175	(7)
The Interleukins	182	(1)
Enzymes	183	(3)
Vaccines	186	(1)
Preparation of Antibodies	187	(4)
Genomics	191	(2)
Antisense Technology	193	(1)
Gene Therapy	194	(1)
Afterword	194	(3)
Immunobiologicals	197	(20)
John M. Beale, Jr.
Cells of the Immune System	197	(3)
Immunity	200	(6)
Acquisition of Immunity	206	(11)
Anti-infective Agents	217	(65)
John M. Beale, Jr.
Evaluation of the Effectiveness of a Sterilant	219	(1)
Alcohols and Related Compounds	219	(2)
Phenols and Their Derivatives	221	(2)
Oxidizing Agents	223	(1)
Halogen-Containing Compounds	223	(1)
Cationic Surfactants	224	(2)
Dyes	226	(2)
Mercury Compounds (Mercurials)	228	(1)
Preservatives	228	(2)
Antifungal Agents	230	(17)
Synthetic Antibacterial Agents	247	(12)
Antiprotozoal Agents	259	(5)
Anthelmintics	264	(4)
Antiscabious and Antipedicular Agents	268	(1)
Antibacterial Sulfonamides	268	(11)
Dihydrofolate Reductase Inhibitors	279	(1)
Sulfones	279	(3)
Antimalarials	282	(17)
John H. Block
Stimulation of Antimalarial Research by War	283	(2)
Drug Therapy	285	(1)
Cinchona Alkaloids	286	(13)
Antibacterial Antibiotics	299	(68)
John M. Beale, Jr.
Historical Background	299	(1)
Current Status	299	(1)
Commercial Production	300	(1)
Spectrum of Activity	300	(1)
Mechanisms of Action	300	(1)
Chemical Classification	301	(1)
Microbial Resistance	301	(1)
β-Lactam Antibiotics	301	(1)
The Penicillins	302	(12)
β-Lactamase Inhibitors	314	(4)
Cephalosporins	318	(16)
Monobactams	334	(1)
Aminoglycosides	334	(7)
Tetracyclines	341	(8)
Macrolides	349	(4)
Lincomycins	353	(2)
Polypeptides	355	(5)
Unclassified Antibiotics	360	(7)
Antiviral Agents	367	(23)
John M. Beale, Jr.
Classification of Viruses	367	(1)
Targets for the Prevention of Viral Infections---Chemoprophylaxis	367	(3)
The Infectious Process for a Virus	370	(5)
Nucleoside Antimetabolites	375	(7)
Newer Agents for the Treatment of HIV Infection	382	(8)
Antineoplastic Agents	390	(64)
William A. Remers
Tumor Cell Properties	390	(4)
Alkylating Agents	394	(8)
Antimetabolites	402	(12)
Antibiotics	414	(10)
Plant Products	424	(4)
Miscellaneous Compounds	428	(5)
Hormones	433	(5)
Signal Transduction Inhibitors	438	(2)
Immunotherapy	440	(2)
Monoclonal Antibodies	442	(2)
Radiotherapeutic Agents	444	(1)
Cytoprotective Agents	445	(1)
Future Antineoplastic Agents	446	(2)
Potential Future Developments	448	(6)
Agents for Diagnostic Imaging	454	(31)
Tim B. Hunter
T. Kent Walsh
Jack N. Hall
Introduction to Radiation	454	(2)
Characteristics of Decay	456	(1)
Biological Effects of Radiation	457	(1)
Radionuclides and Radiopharmaceuticals for Organ Imaging	458	(3)
Radionuclide Production	461	(2)
Technetium Radiochemistry	463	(5)
Fluorine Radiochemistry	468	(1)
Gallium Radiochemistry	468	(1)
Iodine Radiochemistry	468	(1)
Indium Radiochemistry	469	(3)
Thallium Radiochemistry	472	(1)
Xenon Radiochemistry	472	(1)
Radiological Contrast Agents	472	(3)
Paramagnetic Compounds	475	(2)
Ultrasound Contrast Agents	477	(1)
Radiological Procedures	478	(7)
Central Nervous System Depressants	485	(25)
Eugene I. Isaacson
General Anesthetics	485	(3)
Anxiolytic, Sedative, and Hypnotic Agents	488	(8)
Antipsychotics	496	(7)
Anticonvulsant or Antiepileptic Drugs	503	(7)
Central Nervous System Stimulants	510	(14)
Eugene I. Isaacson
Analeptics	510	(1)
Methylxanthines	511	(1)
Central Sympathomimetic Agents (Psychomotor Stimulants)	512	(2)
Antidepressants	514	(6)
Miscellaneous CNS-Acting Drugs	520	(4)
Adrenergic Agents	524	(24)
Rodney L. Johnson
Adrenergic Neurotransmitters	524	(3)
Adrenergic Receptors	527	(1)
Drugs Affecting Adrenergic Neurotransmission	528	(2)
Sympathomimetic Agents	530	(9)
Adrenergic Receptor Antagonists	539	(9)
Cholinergic Drugs and Related Agents	548	(48)
George H. Cocolas
Stephen J. Cutler
Cholinergic Receptors	548	(5)
Cholinergic Neurochemistry	553	(1)
Cholinergic Agonists	553	(5)
Cholinergic Receptor Antagonists	558	(14)
Cholinergic Blocking Agents	572	(1)
Parasympathetic Postganglionic Blocking Agents	573	(1)
Solanaceous Alkaloids and Analogues	574	(5)
Synthetic Cholinergic Blocking Agents	579	(7)
Ganglionic Blocking Agents	586	(3)
Neuromuscular Blocking Agents	589	(7)
Diuretics	596	(26)
Daniel A. Koechel
Anatomy and Physiology of the Nephron	596	(1)
Function	596	(5)
Introduction to the Diuretics	601	(2)
Site 1 Diuretics: Carbonic Anhydrase Inhibitors	603	(2)
Site 3 Diuretics: Thiazide and Thiazide-Like Diuretics	605	(5)
Site 2 Diuretics: High-Ceiling or Loop Diuretics	610	(6)
Site 4 Diuretics: Potassium-Sparing Diuretics	616	(2)
Miscellaneous Diuretics	618	(1)
Emerging Developments in the Use of Diuretics to Treat Hypertension and Congestive Heart Failure	618	(1)
Summary	619	(1)
Diuretic Preparations	619	(3)
Cardiovascular Agents	622	(54)
Stephen J. Cutler
George H. Cocolas
Antianginal Agents and Vasodilators	622	(12)
Antiarrhythmic Drugs	634	(8)
Antihypertensive Agents	642	(15)
Antihyperlipidemic Agents	657	(6)
Anticoagulants	663	(5)
Synthetic Hypoglycemic Agents	668	(5)
Thyroid Hormones	673	(1)
Antithyroid Drugs	673	(3)
Local Anesthetic Agents	676	(20)
Gareth Thomas
Historical Development	676	(3)
The Nervous System	679	(6)
Mechanism of Action	685	(2)
Administration	687	(1)
Factors Influencing the Effectiveness of the Anesthetic Action	687	(1)
Rate of Onset and Duration of Anesthesia	688	(1)
Secondary Pharmacological Action	689	(1)
Structure Action	690	(6)
Histamine and Antihistaminic Agents	696	(35)
Thomas N. Riley
Jack DeRuiter
Histamine	696	(1)
Histamine Life Cycle	696	(4)
Histamine H1 Antagonists (Antihistaminic Agents)	700	(15)
Inhibition of Histamine Release: Mast Cell Stabilizers	715	(2)
Recent Antihistamine Developments: The ``Dual-Acting'' Antihistamines	717	(1)
Histamine H2 Antagonists	718	(9)
Histamine H3-Receptor Ligands	727	(4)
Analgesic Agents	731	(36)
Robert E. Willette
Pain	731	(1)
Morphine and Related Compounds	732	(20)
Antitussive Agents	752	(1)
Anti-inflammatory Analgesics	753	(14)
Steroids and Therapeutically Related Compounds	767	(51)
Philip J. Proteau
Steroid Nomenclature, Stereochemistry, and Numbering	767	(1)
Steroid Biosynthesis	768	(2)
Chemical and Physical Properties of Steroids	770	(1)
Changes to Modify Pharmacokinetic Properties of Steroids	770	(1)
Steroid Hormone Receptors	770	(3)
GnRH and Gonadotropins	773	(2)
Sex Hormones	775	(14)
Chemical Contraceptive Agents	789	(8)
Androgens	797	(6)
Adrenal Cortex Hormones	803	(15)
Prostaglandins, Leukotrienes, and Other Eicosanoids	818	(12)
Thomas J. Holmes, Jr.
History of Discovery	818	(1)
Eicosanoid Biosynthesis	818	(4)
Drug Action Mediated by Eicosanoids	822	(1)
COX-2 Inhibitors	822	(1)
Design of Eicosanoid Drugs	823	(1)
Development of Prostacyclin-Derived Products	823	(2)
Eicosanoid Receptors	825	(2)
Eicosanoids Approved for Human Clinical Use	827	(1)
Prostaglandins for Ophthalmic Use	828	(1)
Veterinary Uses of Prostanoids	828	(1)
Eicosanoids in Clinical Development for Human Treatment	829	(1)
Proteins, Enzymes, and Peptide Hormones	830	(36)
Stephen J. Cutler
Horace G. Cutler
Protein Hydrolysates	830	(1)
Amino Acid Solutions	830	(1)
Proteins and Protein-Like Compounds	831	(4)
Enzymes	835	(5)
Hormones	840	(17)
Blood Proteins	857	(1)
Impact of Biotechnology on the Development and Commercial Production of Proteins and Peptides as Pharmaceutical Products	858	(2)
Biotechnology-Derived Pharmaceutical Products	860	(6)
Vitamins and Related Compounds	866	(38)
Gustavo R. Ortega
Michael J. Deimling
Jaime N. Delgado
Lipid-Soluble Vitamins	867	(18)
Water-Soluble Vitamins	885	(15)
Miscellaneous Considerations	900	(4)
An Introduction to the Medicinal Chemistry of Herbs	904	(15)
John M. Beale, Jr.
What is an Herb?	905	(1)
Herbal Purity and Standardization	905	(1)
An Herb Is a Drug	905	(1)
Types of Herbs	906	(13)
Computational Chemistry and Computer-Assisted Drug Design	919	(29)
J. Phillip Bowen
Computer Graphics and Molecular Visualization	920	(2)
Computational Chemistry Overview	922	(1)
Force Field Methods	923	(6)
Geometry Optimization	929	(1)
Conformational Searching	930	(3)
Molecular Dynamics Simulations	933	(2)
Quantum Mechanics	935	(4)
Structure-Based Drug Design and Pharmacophore Perception	939	(5)
Predictive ADME	944	(4)
Appendix Calculated Log P, Log D, and pKa	948	(9)
Index	957