ABSTRACT
Accelerating the drug discovery process by finding new chemical moieties (NCEs) faster is a major objective in the field of medical research. Hunting for a drug among the vast numbers of chemotypes, is a daunting task as is evidenced by the small number of molecules that are approved as drugs even though significant resources are expended on this activity. The drug discovery process generally involves identification of a validated biological target (enzyme, receptor, DNA & RNA) and developing a biological assay to hunt for novel chemotypes as a starting point for drug design. After finding a novel chemotype with the required biological activity multiple rounds of optimization with respect to pharmacokinetics and drug metabolism lead to clinical candidates. Drug hunters have evolved various strategies in order to perform this task efficiently, among these combinatorial chemistry is a strategy that has been used to efficiently sample the large chemical space that is available to them. The starting point or the initial discovery of a novel chemotype with the required biological activity is often called a “lead compound” and this phase of drug discovery is often called the “lead discovery” phase. A suitable lead compound is a small molecule with measurable and reproducible activity in the primary assay(s). In case the target is unknown then random screening may be need to test many thousands or millions of compounds in order to discover a lead. Combinatorial chemistry is designed to support the lead discovery process. It is a technique by which a large number of structurally distinct molecules can be synthesized together at a time and submitted for focused or varied pharmacological assay. Combinatorial chemistry has enabled the identification of many leads in drug discovery programs.
