Drug discovery is a very expensive and time consuming process. For approximately every 10,000 compounds that are evaluated in animal studies, 10 will make it to human clinical trials in order to get 1 compound on the market.
Once the new drug application (NDA) is submitted to the food and drug administration (FDA), it can be several months to several years before it is approved for therapeutic use.
The discovery or design of a new drug not only requires a discovery or design process but also the synthesis of the drug, a method of administration, the development of tests and procedures to establish how it operates in the body and a safety assessment. Drug discovery may also require fundamental research into the biological and chemical nature of the diseased state. These and other aspects of drug design and discovery require input from specialists in many other fields and so medicinal chemists need to have an outline knowledge of the relevant aspects of these fields.
Actually, drugs are not discovered. What is more likely discovered is known as a lead compound. The lead is a prototype compound that has a number of attractive characteristics, such as the desired biological or pharmacological activity, but may have other undesirable characteristics such as high toxicity, absorption difficulties, insolubility, or metabolism related problems.
Nowadays, there are three major sources for lead compounds- Natural, Synthetic and Semisynthetic.
Once the lead compound identified, the structure of the lead compound is modified by the synthesis to amplify the desired activity and to minimize or eliminate the unwanted properties to a point where a drug candidate, a compound worthy of extensive biological, pharmacological and animal studies, is identified; then a clinical drug, a compound ready for clinical trials, is developed.
Great progress has been made in the development and application of methodology to facilitate both drug lead generation and lead optimization. Serendipity has always played a large part in the discovery of drugs. For example, the development of penicillin by Florey and Chain was only possible because Alexander Fleming noted the inhibition of staphylococcus by “Penicillium notatum”. In spite of our increased knowledge base, it is still necessary to pick the correct starting point for an investigation if a successful outcome is to be achieved and luck still plays a part in selecting that point. This state of affairs will not change and undoubtedly luck will also lead to new discoveries in the future. However, modern techniques such as computerised molecular modelling and combinatorial chemistry introduced in the 1970s and 1990s, respectively, are likely to reduce the number of intuitive discoveries.
Two of the factors necessary for drug action are that the drug fits and binds to the target. Molecular modelling allows the researcher to predict the three-dimensional shapes of molecules and target. It enables workers to check whether the shape of a potential lead is complementary to the shape of its target. It also allows one to calculate the binding energy liberated when a molecule binds to its target. Molecular modelling has reduced the need to synthesise every analogue of a lead compound. It is also often used retrospectively to confirm the information derived from other sources. Combinatorial chemistry originated in the field of peptide chemistry but has now been expanded to cover other areas. It is a group of related techniques for the simultaneous production of large numbers of compounds, known as libraries, for biological testing. Consequently, it is used for structure–activity studies and to discover new lead compounds. The procedures may be automated.