title: Substituted 3-amino biaryl propionic acids as potent VLA-4 antagonists.
abstract: A series of substituted N-(3,5-dichlorobenzenesulfonyl)-(L)-prolyl- and (L)-azetidyl-beta-biaryl beta-alanine derivatives was prepared as selective and potent VLA-4 antagonists. The 2,6-dioxygenated biaryl substitution pattern is important for optimizing potency. Oral bioavailability was variable and may be a result of binding to circulating plasma proteins.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. ihor_kopka@merck.com
authors.forename: Ihor E
authors.initials: IE
authors.lastname: Kopka
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mumford
authors.forename: Thomas
authors.initials: T
authors.lastname: Lanza
authors.forename: Plato A
authors.initials: PA
authors.lastname: Magriotis
authors.forename: David
authors.initials: D
authors.lastname: Young
authors.forename: Stephen E
authors.initials: SE
authors.lastname: DeLaszlo
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Sander G
authors.initials: SG
authors.lastname: Mills
authors.forename: Gail
authors.initials: G
authors.lastname: Van Riper
authors.forename: Ermengilda
authors.initials: E
authors.lastname: McCauley
authors.forename: Kathryn
authors.initials: K
authors.lastname: Lyons
authors.forename: Stella
authors.initials: S
authors.lastname: Vincent
authors.forename: Linda A
authors.initials: LA
authors.lastname: Egger
authors.forename: Usha
authors.initials: U
authors.lastname: Kidambi
authors.forename: Ralph
authors.initials: R
authors.lastname: Stearns
authors.forename: Adria
authors.initials: A
authors.lastname: Colletti
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Teffera
authors.forename: Sharon
authors.initials: S
authors.lastname: Tong
authors.forename: Karen
authors.initials: K
authors.lastname: Owens
authors.forename: Dorothy
authors.initials: D
authors.lastname: Levorse
authors.forename: John A
authors.initials: JA
authors.lastname: Schmidt
authors.forename: William K
authors.initials: WK
authors.lastname: Hagmann
mesh_terms: D000284:Administration, Oral; D000409:Alanine / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D006801:Humans; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D019169:Jurkat Cells; D008657:Metabolic Clearance Rate; D011422:Propionates / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D039041:Integrin alpha4beta1; D011422:Propionates; D019010:Vascular Cell Adhesion Molecule-1; D000409:Alanine