Fundamentals of Medicinal Chemistry / Edition 1

Fundamentals of Medicinal Chemistry / Edition 1

by Gareth Thomas, Thomas Gareth
     
 

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ISBN-10: 0470843071

ISBN-13: 9780470843079

Pub. Date: 12/01/2003

Publisher: Wiley

Provides a concise introduction to the chemistry of therapeutically active compounds, written in a readable and accessible style.

The title begins by reviewing the structures and nomenclature of the more common classes of naturally occurring compounds found in biological organisms. An overview of medicinal chemistry is followed by chapters covering the discovery

Overview

Provides a concise introduction to the chemistry of therapeutically active compounds, written in a readable and accessible style.

The title begins by reviewing the structures and nomenclature of the more common classes of naturally occurring compounds found in biological organisms. An overview of medicinal chemistry is followed by chapters covering the discovery and design of drugs, pharmacokinetics and drug metabolism, The book concludes with a chapter on organic synthesis, followed by a brief look at drug development from the research stage through to marketing the final product.

The text assumes little in the way of prior biological knowledge. relevant biology is included through biological topics, examples and the Appendices.

  • Incorporates summary sections, examples, applications and problems
  • Each chapter contains an additional summary section and solutions to the questions are provided at the end of the text
  • Invaluable for undergraduates studying within the chemical, pharmaceutical and life sciences.

Product Details

ISBN-13:
9780470843079
Publisher:
Wiley
Publication date:
12/01/2003
Edition description:
New Edition
Pages:
302
Product dimensions:
7.50(w) x 9.80(h) x 0.70(d)

Related Subjects

Table of Contents

Prefacexi
Acknowledgementsxii
Abbreviations/Acronymsxiii
1Biological Molecules1
1.1Introduction1
1.2Amino acids1
1.2.1Introduction1
1.2.2Structure3
1.2.3Nomenclature3
1.3Peptides and proteins4
1.3.1Structure6
1.4Carbohydrates10
1.4.1The structure of monosaccharides11
1.4.2The nomenclature of monosaccharides14
1.4.3Glycosides15
1.4.4Polysaccharides17
1.4.5The nomenclature of polysaccharides18
1.4.6Naturally occurring polysaccharides18
1.5Lipids20
1.5.1Introduction20
1.5.2Fatty acids20
1.5.3Acylglycerols (glycerides)21
1.5.4Steroids21
1.5.5Terpenes22
1.5.6Phospholipids23
1.5.7Glycolipids25
1.6Nucleic acids26
1.6.1Introduction26
1.6.2DNA, structure and replication28
1.6.3Genes and the human genome project30
1.6.4RNA, structure and transcription31
1.6.5Classification and function of RNA33
1.7Questions34
2An Introduction to Drugs and their Action37
2.1Introduction37
2.2What are drugs and why do we need new ones?37
2.3Drug discovery and design, a historical outline39
2.4Sources of drugs and lead compounds43
2.4.1Natural sources43
2.4.2Drug synthesis45
2.4.3Market forces and 'me-too drugs'45
2.5Classification of drugs45
2.6Routes of administration, the pharmaceutical phase46
2.7Introduction to drug action49
2.7.1The pharmacokinetic phase49
Absorption49
Distribution50
Metabolism51
Elimination51
2.7.2Bioavailability of a drug53
2.7.3The pharmacodynamic phase53
2.8Questions55
3An Introduction to Drug Discovery57
3.1Introduction57
3.2Stereochemistry and drug design59
3.2.1Structurally rigid groups59
3.2.2Conformation60
3.2.3Configuration60
3.3Solubility and drug design61
3.3.1The importance of water solubility62
3.4Solubility and drug structure63
3.5Salt formation64
3.6The incorporation of water solubilizing groups in a structure65
3.6.1The type of group66
3.6.2Reversibly and irreversibly attached groups66
3.6.3The position of the water solubilizing group67
3.6.4Methods of introduction67
3.7Questions70
4The SAR and QSAR Approaches to Drug Design71
4.1Structure-activity relationships (SARs)71
4.2Changing size and shape73
4.3Introduction of new substituents73
4.3.1The introduction of a group in an unsubstituted position73
4.3.2The introduction of a group by replacing an existing group76
4.4Quantitative structure-activity relationships (QSARs)78
4.4.1Lipophilicity79
Partition coefficients (P)79
Lipophilic substitution constants ([pi])80
4.4.2Electronic effects82
The Hammett constant ([sigma])82
4.4.3Steric effects83
The Taft steric parameter (E[subscript s])84
Molar refractivity (MR)84
Other parameters85
4.4.4Hansch analysis85
Craig plots88
4.5The Topliss decision tree89
4.6Questions92
5Computer Aided Drug Design95
5.1Introduction95
5.1.1Molecular modelling methods96
5.1.2Computer graphics98
5.2Molecular mechanics98
5.2.1Creating a molecular model using molecular mechanics102
5.3Molecular dynamics104
5.3.1Conformational analysis105
5.4Quantum mechanics105
5.5Docking109
5.6Questions110
6Combinatorial Chemistry113
6.1Introduction113
6.1.1The design of combinatorial syntheses115
6.1.2The general techniques used in combinatorial synthesis116
6.2The solid support method117
6.2.1Parallel synthesis118
6.2.2Furka's mix and split technique121
6.3Encoding methods123
6.3.1Sequential chemical tagging methods123
6.3.2Still's binary code tag system124
6.3.3Computerized tagging126
6.4Combinatorial synthesis in solution127
6.5Screening and deconvolution128
6.6Questions130
7Selected Examples of Drug Action at some Common Target Areas131
7.1Introduction131
7.2Examples of drugs that disrupt cell membranes and walls131
7.2.1Antifungal agents132
Azoles133
Allylamines134
Phenols135
7.2.2Antibacterial apents135
Ionophoric antibiotic action135
Cell wall synthesis inhibition136
7.3Drugs that target enzymes138
7.3.1Reversible inhibihors139
7.3.2Irreversible inhibition140
7.3.3Transition state inhibitors142
7.4Drugs that target receptors144
7.4.1Agonists144
7.4.2Antagonists145
7.4.3Partial agonists147
7.5Drugs that target nucleic acids147
7.5.1Antimetabolites147
7.5.2Enzyme inhibitors150
7.5.3Intercalation agents151
7.5.4Alkylating agents152
7.5.5Antisense drugs152
7.5.6Chain cleaving agents154
7.6Antiviral drugs155
7.6.1Nucleic acid synthesis inhibitors155
7.6.2Host cell penetration inhibitors156
7.6.3Inhibitors of viral protein synthesis157
7.7Questions157
8Pharmacokinetics159
8.1Introduction to pharmacokinetics159
8.1.1General classification of pharmacokinetic properties160
8.2Pharmacokinetics and drug design160
8.3Pharmacokinetic models161
8.4Intravascular administration162
8.4.1Intravenous injection (IV bolus)163
8.4.2Clearance and its significance166
8.4.3Intravenous infusion169
8.5Extravascular administration171
8.5.1Single oral dose174
8.5.2The calculation of t[subscript max] and C[subscript max]176
8.5.3Repeated oral doses176
8.6The use of pharmacokinetics in drug design177
8.7Questions178
9Drug Metabolism181
9.1Introduction181
9.1.1The stereochemistry of drug metabolism181
9.1.2Biological factors affecting metabolism183
9.1.3Environmental factors affecting metabolism184
9.1.4Species and metabolism184
9.2Secondary pharmacological implications of metabolism184
9.3Sites of action184
9.4Phase I metabolic reactions186
9.4.1Oxidation186
9.4.2Reduction186
9.4.3Hydrolysis189
9.4.4Hydration189
9.4.5Other Phase I reactions189
9.5Phase II metabolic routes190
9.6Pharmacokinetics of metabolites190
9.7Drug metabolism and drug design193
9.8Prodrugs195
9.8.1Bioprecursor prodrugs195
9.8.2Carrier prodrugs196
9.8.3The design of prodrug systems for specific purposes197
Improving absorption and transport through membranes197
Improving patient acceptance198
Slow release198
Site specificity198
Minimizing side effects200
9.9Questions200
10An Introduction to Lead and Analogue Syntheses203
10.1Introduction203
10.2Asymmetry in syntheses205
10.2.1The use of non-stereoselective reactions to produce stereospecific centres206
10.2.2The use of stereoselective reactions to produce stereospecific centres207
10.2.3General methods of asymmetric synthesis208
Methods that use catalysts to obtain stereoselectivity210
Methods that do not use catalysts to obtain stereoselectivity211
10.3Designing organic syntheses214
10.3.1An introduction to the disconnection approach214
10.4Questions220
11Drug Development and Production223
11.1Introduction223
11.2Chemical development224
11.2.1Chemical engineering issues225
11.2.2Chemical plant, health and safety considerations226
11.2.3Synthesis quality control227
11.2.4A case study228
11.3Pharmacological and toxicological testing231
11.4Drug metabolism and pharmacokinetics234
11.5Formulation development235
11.6Production and quality control235
11.7Patent protection236
11.8Regulation237
11.9Questions238
Appendix239
A.1Sickle-cell anaemia239
A.2Bacteria240
A.3Cell membranes244
A.4Receptors246
A.5Transfer through membranes249
A.6Regression analysis250
A.7Enzymes252
A.8Prostaglandins255
A.9Cancer256
A.10Viruses257
A.11Blood-brain barrier259
A.12Enzyme structure and species260
Answers to Questions261
Selected Further Reading273
Index275

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