title: Selective cell adhesion inhibitors: Barbituric acid based alpha4beta7--MAdCAM inhibitors.
abstract: A novel series of barbituric acid derivatives were identified as selective inhibitors of alpha4beta7 MAdCAM (mucosal addressin cell adhesion molecule-1) interactions via a high throughput screening exercise. These inhibitors were optimized to submicromolar potencies in whole cell adhesion assays, retaining their selectivity over alpha4beta1 VCAM.
authors.affiliation: Millennium Pharmaceuticals, 35 Landsdowne Street, Cambridge, MA 02139, USA. gharriman@galenea.com
authors.forename: Geraldine C
authors.initials: GC
authors.lastname: Harriman
authors.forename: Matthias
authors.initials: M
authors.lastname: Brewer
authors.forename: Robert
authors.initials: R
authors.lastname: Bennett
authors.forename: Cyrille
authors.initials: C
authors.lastname: Kuhn
authors.forename: Marc
authors.initials: M
authors.lastname: Bazin
authors.forename: Greg
authors.initials: G
authors.lastname: Larosa
authors.forename: Paul
authors.initials: P
authors.lastname: Skerker
authors.forename: Nancy
authors.initials: N
authors.lastname: Cochran
authors.forename: Debra
authors.initials: D
authors.lastname: Gallant
authors.forename: Deborah
authors.initials: D
authors.lastname: Baxter
authors.forename: Dominic
authors.initials: D
authors.lastname: Picarella
authors.forename: Bruce
authors.initials: B
authors.lastname: Jaffee
authors.forename: Jay R
authors.initials: JR
authors.lastname: Luly
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Briskin
mesh_terms: D000818:Animals; D001463:Barbiturates / Q000138:chemical synthesis / Q000494:pharmacology*; D001665:Binding Sites; D002448:Cell Adhesion / Q000187:drug effects* / Q000502:physiology; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins / Q000378:metabolism; D039041:Integrin alpha4beta1 / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008956:Models, Chemical; D009088:Mucoproteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D001463:Barbiturates; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D039041:Integrin alpha4beta1; D016023:Integrins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D019010:Vascular Cell Adhesion Molecule-1; C071777:integrin alpha4beta7; C032232:barbituric acid