Chapter 2 - Drug Discovery, Design, and Development

Abstract

This chapter presents an overview of drug discovery, drug design and developments, quantitative structure-activity relationships, and molecular graphics-based drug design. Drug discovery is a time-consuming and expensive process. Estimates of the average time required to bring a drug to the market ranges from 12 to15 years at an average cost of about $800 million. Rational approaches to drug design are the major routes to leaddiscovery. It is impossible to foretell the toxicity and side effects of a drug, anticipate its transport characteristics, or predict the metabolic fate of a drug. An important physicochemical parameter in lead discovery/lead optimization lies in steric effects, particularly for receptor binding. As a lead is identified, its structure is modified until an effective drug is obtained. Only a small part of the lead compound is involved in receptor interactions. The relevant groups on a molecule that interact with a receptor and are responsible for the activity are collectively known as the pharmacophore. A medicinal chemist tinkers the drug design parameters to augment the potency, selectivity, and duration of the drug's action and to reduce the toxicity of the drug. The concept of quantitative drug design is based on the fact that the biological properties of a compound are a function of its physicochemical parameters.