Medicinal Chemistry

2.5 Classical Theories of Drug–Receptor Binding Interactions 78
2.6 Experimental Quantification of Drug–Receptor
Binding Interactions 81
2.7 General Molecular Concepts of Drug Receptor Action 84
2.8 Receptor Action: Regulation, Metabolism,
and Dynamics 90
2.9 Receptor Types as Determined by Molecular
Mode of Action 92
2.10 Receptor Action: Mechanisms in Receptor
Signal Transduction 93
2.11 Selecting a Receptor Appropriate for Drug Design 96
2.12 The Clinical–Molecular Interface: The Concept
of Rational Polypharmacy 101
Selected References 103

3. Basic Principles of Drug Design III—Designing
   Drug Molecules to Fit Receptors 106
   3.1 Overall Strategy: The Multiphore Method of
   Drug Design 106
   3.2 Identification of a Lead Compound 108
   3.3 Synthesis of a Lead Compound 128
   3.4 Optimizing the Lead Compound:
   The Pharmacodynamic Phase 134
   3.5 Optimizing the Lead Compound: Pharmacokinetic
   and Pharmaceutical Phases 146
   3.6 From Lead Discovery to Clinical Trials:
   The Concept of a “Useful Drug” 159
   Selected References 163
   Appendix 3.1: Basic Reactions for Drug Molecule Synthesis 166

II BIOCHEMICAL CONSIDERATIONS IN DRUG DESIGN:

FROM DRUGGABLE TARGETS TO DISEASES

Introduction to Part II 185

The Physiological Systems Approach 186

The Pathological Process Approach 186

The Molecular Messenger and Nonmessenger Target System 188

4. Messenger Targets for Drug Action I:
   Neurotransmitters and Their Receptors 193
   4.1 Overview of Relevant Neuroanatomy and Neurophysiology 193
   4.2 Acetylcholine and the Cholinergic Receptors 204
   4.3 Norepinephrine and the Adrenergic Receptors 218
   4.4 Dopamine and the Dopaminergic Receptors 238

x MEDICINAL CHEMISTRY