Drug discovery is part luck and part structured investigation. At the beginning of the 19th century it was largely carried out by individuals but it now requires teamwork, the members of the team being specialists in various fields, such as medicine, biochemistry, chemistry, computerized molecular modeling, pharmaceutics, pharmacology, microbiology, toxicology, physiology and pathology.
The approach to drug design depends on the objectives of the design team. These objectives will normally require a detailed assessment of the pathology of the disease and in some cases basic biochemical research will be necessary before initiating a drug design investigation.
The information obtained is used by the team to decide what intervention would be most likely to bring about the desired result. Once the point of intervention has been selected, the team has to propose a structure for a lead compound that could possibly bring about the required change. This frequently requires an extensive literature and database search to identify compounds found in the organism (endogenous compounds) and compounds that are not found in the organism (exogenous compounds) that have some biological effect at the intervention site.
Molecular modeling techniques are sometimes used to help the team reach a decision. In many cases, a number of structures are found to be suitable, but the expense of producing drugs dictates that the team has to choose only one or two of these compounds to either act as the lead or to be the inspiration for the lead compound. The final selection depends on the experience of the team.
Once the structure of the proposed lead has been agreed, it becomes the responsibility of the medicinal chemist to devise a synthetic route and prepare a sample of this compound for testing. Once synthesized, the compound undergoes initial pharmacological and toxicological testing. The results of these tests enable the team to decide whether it is profitable to continue development by preparing analogues, since it is unlikely that the lead compound itself will be suitable for use as a drug.
The general steps in the design of a new drug –
The selection of a lead compound and the development of a synthetic pathway for its preparation is not the only consideration at the start of an investigation. Researchers must also devise suitable in vivo and in vitro tests to assess the activity and toxicity of the compounds produced. There is no point in carrying out an expensive synthetic procedure if at the end of the day it is impossible to test the product.
Solubility and Drug Design
The relative solubility of drugs in the aqueous media and lipid tissues of the body play a major part in their absorption and transport to their sites of action. To pass through a membrane a drug must usually exhibit a reasonable degree of both water and lipid solubility. An appropriate degree of water solubility will often improve drug distribution within the circulatory system as well as drug action.