Bareham J Drug Design

1. Auflage 2014
ISBN: 978-1-4832-9483-4
Verlag: Elsevier Science & Techn.
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band Volume 9, 374 Seiten, Web PDF

Reihe: Medicinal Chemistry

Drug Design, Volume IX examines various aspects of drug design and covers topics ranging from the consequences of the Hansch paradigm for the pharmaceutical industry to the Masca model of pharmacochemistry. A physicochemical basis for the design of orally active prodrugs is also considered, along with the use of interactive graphics in medicinal chemistry. Comprised of seven chapters, this volume begins with a discussion on efforts to avoid toxicity, not only of drugs, pesticides, and food additives but also of chemicals in general. The reader is then introduced to various aspects of the development of bioactive agents, including the optimization of existing agents by the design of more efficient prodrugs. Other chapters focus on Hansch's paradigm and its application to industrial practice; the application of multivariate statistics to pharmacochemistry; a logico-structural approach to computer-assisted drug design; and spatial arrangements in bioactive molecules. This book will be of interest to pharmacologists, chemists, and those involved in drug design.

Autoren/Hrsg.

Bareham J, Bareham

Inhaltsverzeichnis

1;Front Cover;1
2;Drug Design;4
3;Copyright Page;5
4;Table of Contens;6
5;MEDICINAL CHEMISTRY;3
6;List of Contributors;10
7;Preface;12
8;Contents of Other Volumes;14
9;Chapter 1. Design of Safer Chemicals;22
9.1;I. Introduction;22
9.2;II. Toxic Action;23
9.3;III. The Exposure Phase;24
9.4;IV. The Toxokinetic Phase;28
9.5;V. The Toxodynamic Phase;57
9.6;VI. Relationship Between Structure and Toxic Action;58
9.7;VII. Conclusions;134
9.8;ACKNOWLEDGMENT;65
9.9;References;136
10;Chapter 2 Consequences of the Hansch Paradigm
for the Pharmaceutical Industry;68
10.1;I. Introduction;69
10.2;II. Design of Biological Experiments;71
10.3;III. Search for New Leads: The Impossible Dream;77
10.4;IV. Optimization of Lead: An Interactive Approach;94
10.5;V. Drug Designer as "Interlocutor";119
10.6;VI. Methodology;121
10.7;VII. Conclusions;134
10.8;ACKNOWLEDGMENT;136
10.9;References;136
11;Chapter 3 A Physical Chemical Basis for the
Design of Orally Active Prodrugs;142
11.1;I. Introduction;143
11.2;II. Factors Governing Drug Efficiency;144
11.3;III. Approaches to Improved Drug Efficiency;155
11.4;IV. Controlling Physical Properties of Nonelectrolytes;157
11.5;V. Controlling Physical Properties of Weak Electrolytes;177
11.6;VI. Examples of Improved Drug Efficiency;188
11.7;VII. Solubility-Limited Absorption;198
11.8;VIII. Metabolism-Limited Bioavailability;199
11.9;IX. Design of Prodrug Lability;201
11.10;X. Summary and Overview;203
11.11;References;203
12;Chapter 4 The Masca Model of Pharmacochemistry: I. Multivariate
Statistics;208
12.1;I. Introduction;209
12.2;II. General Remarks on Multivariate Statistics;212
12.3;III. Multivariate Bioassay;216
12.4;IV. Reduction of Dimensionality (Principal Component Analysis);223
12.5;V. Multivariate Structure-Activity Analysis;225
12.6;VI. Numerical Examples;236
12.7;VII. Discussion;250
12.8;References;252
13;Chapter 5 Rationales in the Design of Rectal and
Vaginal Delivery Forms of Drugs;258
13.1;I. General Introduction;258
13.2;II. Rectal Delivery Forms;260
13.3;III. Vaginal Delivery Forms;283
13.4;References;285
14;Chapter 6 Interactive Graphics in Medicinal
Chemistry;288
14.1;I. Introduction;289
14.2;II. Applications of Interactive Graphics;290
14.3;III. Hardware and Software;291
14.4;IV. Data Bases and Information-Retrieval Techniques;299
14.5;V. Properties of Molecules and Crystals;301
14.6;VI. Molecular Interactions;302
14.7;VII. A Digital Approach to Drug Design;312
14.8;VIII. Summary;315
14.9;ACKNOWLEDGMENT;316
14.10;References;316
15;Chapter 7 Logico-Structural Approach toComputer-Assisted Drug Design;320
15.1;I. Introduction;321
15.2;II. General Principles of Logico-Structural Approach;324
15.3;III. Activity Feature Selection within Series of Chemical
Compounds;330
15.4;IV. Activity Prediction Using a Data Base on Chemical Structure and
Biological Activity;340
15.5;V. Selection of Topological and Topographical Activity Features;352
15.6;VI. Conclusion;355
15.7;ACKNOWLEDGMENTS;356
15.8;References;356
16;Index;360