Section A-The science of medicinal chemistry 1
A1 Introduction 1
A2 From concept to market 4
Section B-Drug targets 7
B1 Enzymes 7
B2 Receptors 13
B3 Carrier proteins 24
B4 Structural proteins 27
B5 Nucleic acids 29
B6 Lipids 35
B7 Carbohydrates 38
Section C-Pharmacokinetics 41
C1 Pharmacokinetics 41
C2 Drug absorption 42
C3 Drug distribution 45
C4 Drug metabolism 48
C5 Drug excretion 51
C6 Drug administration 54
C7 Drug dosing 58
Section D-Biological testing and bioassays 61
D1 Testing drugs 61
D2 Testing drugs in vitro 62
D3 Testing drugs in vivo 70
Section E-Drug discovery 75
E1 The lead compound 75
E2 Natural sources of lead compounds 77
E3 Synthetic sources of lead compounds 82
F1 Synthetic considerations 85
Section F-Synthesis 85
F2 Stereochemistry 90
F3 Combinatorial synthesis 100
Section G-Structure-activity relationships 105
G1 Definition of structure-activity relationships 105
G2 Binding interactions 107
G3 Functional groups as binding groups 110
G4 The pharmacophore 120
G5 Quantitative structure-activity relationships 125
H1 Aims of drug design 141
Section H-Target orientated drug design 141
H2 Computer aided drug design 143
H3 Simplification of complex molecules 148
H4 Conformational restraint 151
H5 Extra binding interactions 155
H6 Enhancing existing binding interactions 160
Section I-Pharmacokinetic orientated drug design 167
I1 Drug solubility 167
I2 Drug stability 171
J1 Patenting and chemical development 177
Section J-Patenting and manufacture 177
J2 Optimization of reactions 181
J3 Scale-up issues 188
J4 Process development 193
J5 Specifications 197
Section K-Preclinical testing and clinical trials 203
K1 Toxicology 203
K2 Pharmacology and pharmaceutical chemistry 205
K3 Drug metabolism studies 207
K4 Clinial trials 212
K5 Regulatory affairs 216
Section L-Case study：inhibitors of EGF-receptor kinase 221
L1 Epidermal growth factor receptor 221
L2 Testing procedures 224
L3 From lead compound to dianilino-phthalimides 226
L4 Modeling studies 233
L5 4-(Phenylamino)pyrrolopyrimidines 239
L6 Pyrazolopyrimidines 241
Section M-History of medicinal chemistry 245
M1 The age of herbs,potions and magic 245
M2 The nineteenth century 247
M3 A fledgling science(1900-1930) 251
M4 The dawn of the antibacterial age(1930-1945) 254
M5 The antibiotic age(1945-1970s) 258
M6 The age of reason(1970s to present) 266
Further reading 271
Index 273