Progress in Medicinal Chemistry : Volume 41

This volume features a comprehensive account of in vitro and in vivo models and in silico approaches for the prediction of oral absorption and bioavailability. It examines the application of virtual screening of virtual libraries as a means of identifying lead molecules for drug discovery programmes. The development of molecular probes targeted to inhibit gamma-secretase, a key enzyme involved in the production of beta-amyloid proteins the accumulation of which has been implicated as a cause of Alzheimer's disease is covered, and progress is reported on the discovery and evaluation of 5-HT terminal autoreceptor antagonists, an approach that may provide a novel treatment of depression. A survey is included of orally acting beta3-agonists for the treatment of type II diabetes and obesity from early compounds active only in rodent models to recent drugs with therapeutic potential in man. Antagonists of the corticotropin releasing factor receptor (CRF) that offer an new approach to the treatment of anxiety and depression, as preliminary clinical data suggests, and possibly of other CNS disorders are also studies, and there is a comprehensive review of inhibitors of phosphodiesterase 5 (PDE5) including compounds that have been advanced into clinical trials.