ABSTRACT

In medicinal chemistry, the discovery of a new lead structure substance represents the most uncertain stage in a drug development program. In the past, the discovery of lead compounds depended essentially upon random occurrences such as accidental observations, fortuitous findings, hearsay or laborious screening of a large number of molecules. More recently, more rational approaches have become available, based on the knowledge of structures of the endogenous metabolites and receptors or on the nature of the biochemical disorder implied in the disease at molecular level. Nowadays there are different strategies to obtain lead structure candidates. These methods may consist of more or less intuitive approaches, such as the synthesis of analogues, isomers and bioisosters or they may be based on computer-assisted design, such as identifying pharmacophores by molecular modeling, Structure-Activity Relationship (SAR) or Quantitative SAR (QSAR) studies (Enriz, 2005).