Ligand design for alpha, adrenoceptors

An area of continuing interest in medicinal chemistry is the design, synthe sis and pharmacological evaluation of ligands which bind at adrenoceptor su btypes, which include alpha (1A), alpha (1B), alpha (1D); alpha (2A), alpha (2B), alpha (2C); beta (1), beta (2), beta (3) and possibly beta (4) subty pes. The selective blockade or stimulation of these receptor subtypes is of on-going pharmacological and medicinal interest. However, the design princ iples for ligand differentiation at these subtypes still need further devel opment. This review focuses on al adrenoceptors with a concentration on lit erature over the past five years. Structural, physiological and therapeutic aspects of the alpha (1A), alpha (1B) and alpha (1D) subtypes are discusse d together with ligands binding to these receptor subtypes. Approaches to a l adrenoceptor ligand design based on known ligands and on receptor docking are evaluated. A new combined approach using pharmacophores and receptor d ocking affords possibilities for deeper insights into achieving small molec ule binding selectivity.