D.C. Rees Pages 145 - 158 ( 14 )
This article reviews some of the successful approaches made by medicinal chemists to discover non-peptide structures (peptide mimetics, peptidomimetics, peptoids) which act as agonists or antagonists at some of the membrane-bound receptors for endogenous peptides. Three fundamentally different strategies for the discovery of such ligands are discussed. Firstly, broad screening of as many compounds as possible from chemical databases to furnish an initial chemical lead which is subsequently modified to optimise biological activity. Secondly, a design strategy starting with the chemical structure of a known peptide antagonist or an endogenous agonist and modifying this into a non-peptide which incorporates elements of the peptide structure. Thirdly, a strategy of modifying the chemical structure of a previously reported non-peptide lead. These strategies are illustrated with examples of non peptide ligands for receptor subtypes of cholecystokinin (CCK), the neurokinins, the opioids, vasopressin, oxytocin, endothelin, angiotensin, neurotensin and bombesin.