title: Dehydrophenylalanine derivatives as VLA-4 integrin antagonists.
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.
authors.affiliation: Department of Medicinal Chemistry, Celltech R&D Ltd, 216 Bath Road, Slough SL1 4EN, UK. john.porter@celltechgroup.com
authors.forename: John R
authors.initials: JR
authors.lastname: Porter
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Archibald
authors.forename: Julien A
authors.initials: JA
authors.lastname: Brown
authors.forename: Kirstie
authors.initials: K
authors.lastname: Childs
authors.forename: David
authors.initials: D
authors.lastname: Critchley
authors.forename: John C
authors.initials: JC
authors.lastname: Head
authors.forename: Ted A H
authors.initials: TA
authors.lastname: Parton
authors.forename: Martyn K
authors.initials: MK
authors.lastname: Robinson
authors.forename: Anthony
authors.initials: A
authors.lastname: Shock
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Taylor
authors.forename: Graham J
authors.initials: GJ
authors.lastname: Warrellow
mesh_terms: D000818:Animals; D001569:Benzodiazepines / Q000737:chemistry / Q000494:pharmacology; D001659:Biliary Tract / Q000378:metabolism; D015195:Drug Design; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D007536:Isomerism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D039041:Integrin alpha4beta1; D001569:Benzodiazepines; D010649:Phenylalanine; C018632:phenyldehydroalanine