title: N-Tetrahydrofuroyl-(L)-phenylalanine derivatives as potent VLA-4 antagonists.
abstract: Given the proposed involvement of VLA-4 in inflammatory processes, a program to identify orally active VLA-4 antagonists was initiated. Herein, we report the discovery of a N-tetrahydrofuroyl-(L)-phenylalanine derivative (17) and related analogues as potent VLA-4 antagonists with good oral bioavailability.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. ginger_yang@merck.com
authors.forename: Ginger X
authors.initials: GX
authors.lastname: Yang
authors.forename: Linda L
authors.initials: LL
authors.lastname: Chang
authors.forename: Quang
authors.initials: Q
authors.lastname: Truong
authors.forename: George A
authors.initials: GA
authors.lastname: Doherty
authors.forename: Plato A
authors.initials: PA
authors.lastname: Magriotis
authors.forename: Stephen E
authors.initials: SE
authors.lastname: de Laszlo
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: Usha
authors.initials: U
authors.lastname: Kidambi
authors.forename: Linda A
authors.initials: LA
authors.lastname: Egger
authors.forename: Ermengilda
authors.initials: E
authors.lastname: McCauley
authors.forename: Gail
authors.initials: G
authors.lastname: Van Riper
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mumford
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; D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D004305:Dose-Response Relationship, Drug; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D008253:Macaca mulatta; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D005663:Furans; D039041:Integrin alpha4beta1; D013449:Sulfonamides; D019010:Vascular Cell Adhesion Molecule-1; C018674:tetrahydrofuran; D010649:Phenylalanine