title: Amidines as amide bond replacements in VLA-4 antagonists.
abstract: VLA-4 (alpha(4)beta(1), very late activating antigen-4), a key cell surface integrin plays an important role in inflammation by promoting leukocyte attachment and extravasation from the vasculature into the peripheral tissues. As such, VLA-4 antagonists may be useful in the treatment, prevention, and suppression of diseases where cell adhesion and migration are important such as asthma, rheumatoid arthritis, and multiple sclerosis. Herein, we report on the discovery, synthesis, and biological evaluation of amidines as small molecule antagonists of VLA-4.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. theodore.kamenecka@merck.com
authors.forename: Theodore M
authors.initials: TM
authors.lastname: Kamenecka
authors.forename: You-Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Linus S
authors.initials: LS
authors.lastname: Lin
authors.forename: Stephen
authors.initials: S
authors.lastname: de Laszlo
authors.forename: Ermengilda D
authors.initials: ED
authors.lastname: McCauley
authors.forename: Gail
authors.initials: G
authors.lastname: Van Riper
authors.forename: Linda
authors.initials: L
authors.lastname: Egger
authors.forename: Usha
authors.initials: U
authors.lastname: Kidambi
authors.forename: Richard A
authors.initials: RA
authors.lastname: Mumford
authors.forename: Sharon
authors.initials: S
authors.lastname: Tong
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Adria
authors.initials: A
authors.lastname: Colletti
authors.forename: Yohannes
authors.initials: Y
authors.lastname: Teffera
authors.forename: Ralph
authors.initials: R
authors.lastname: Stearns
authors.forename: Malcolm
authors.initials: M
authors.lastname: MacCoss
authors.forename: John A
authors.initials: JA
authors.lastname: Schmidt
authors.forename: William K
authors.initials: WK
authors.lastname: Hagmann
mesh_terms: D000577:Amides / Q000737:chemistry*; D000578:Amidines / Q000737:chemistry*; D019540:Area Under Curve; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*
chemical_list: D000577:Amides; D000578:Amidines; D039041:Integrin alpha4beta1