Lead Compound

The goal of the medicinal chemist is to find compounds that have potent effects on given diseases with minimum side effects. In other words, a drug must react selectively with its target and have minimal negative effects. A drug must get to the right place in the body, at the right concentration, and at the right time. Therefore, a drug must have the appropriate solubility to allow it to be transported to the target cell. If it is taken orally, the drug must be insensitive to the acid conditions of the stomach, and it also must resist enzymatic degradation by the liver before it reaches its target. Finally, it must eventually be either excreted as is or degraded to harmless compounds that can be excreted.

Medicinal agents used by humans since ancient Times provided the starting point for the development of our current arsenal of drugs . The active ingredients were isolated from herbs , berries, roots, and bark used in traditional medicine. Foxglove, for instance, furnished digitoxin, a cardiac stimulant. The bark of the cinchona tree yielded quinine for relief from malaria. Willow bark contains salicylates used to control fever and pain. The sticky juice of the oriental opium poppy provided morphine for severe pain and codeine for the control of a couch. By 1882, more than 50 different herbs were commonly used to make medicines. Many of these herbs wrere grown in the gardens of religious establishments that treated the sick.


Scientists still search the world for plants and berries and the oceans for flora and fauna that might yield new medicinal compounds . Taxol, a compound isolated from the bark of the Pacific yew tree, is a relatively recently recognized anticancer agent.
Once a naturally occurring drug is isolated and its structure determined, it can serve as a prototype in a search for other biologically active compounds . The prototype is called a lead compound ( i.e., a compound that plays a leading role in the search ). Analogs of the lead compound are synthesized in order to find one that might have improved therapeutic properties or fewer side effects. The analog may have a different substituent than the lead compound , a branched chain instead of a straight chain , or a different ring system. Changing the structure of the lead compound is called molecular modification.