Department of Medicinal Chemistry, Celltech R&D Ltd, 216 Bath Road, Slough SL1 4EN, UK. john.porter@celltechgroup.com
Abstract:
We describe a series of dehydrophenylalanine derivatives where the Z isomers are potent VLA-4 antagonists but are subject to rapid biliary clearance and the E isomers have poor activity but have a slower rate of clearance. These configurationally constrained molecules have led to the design of a novel class of benzodiazepine VLA-4 antagonists.