Medicinal chemistry: Through a glass darkly

Abstract

This chapter discusses past, present, and future of medicinal chemistry. The generation of lead structures and their optimization constitutes a central theme of medicinal chemistry. This theme places continuing demands on synthetic chemistry including the specification of new catalytic processes and consideration of chiral interactions Advances in synthetic methodologies notwithstanding, the future of medicinal chemistry makes increasing demands on chiral control, peptidomimetics, and target- and site- specific delivery. Exploration of specific cellular receptors as surrogate entry loci for peptides and proteins offers significant opportunity for target-specific delivery, particularly if combined with mechanisms to selectively enhance the expression of delivery receptors. Antibodies to the transferrin receptors can cross the blood-brain barrier by internalization through these receptors localized in brain capillary endothelial cells. Antibodies conjugated to nerve growth factor deliver the latter to neurons and enhance the survival of cholinergic and noncholinergic neurons transplanted into the eye. Gene transfer technology is exploitable to create both target- and site-specific delivery systems.