Amidines as amide bond replacements in VLA-4 antagonists.
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.
Kamenecka
Theodore M
TM
Department of Medicinal Chemistry, Merck Research Laboratories, Rahway, NJ 07065, USA. theodore.kamenecka@merck.com
Park
You-Jung
YJ
Lin
Linus S
LS
de Laszlo
Stephen
S
McCauley
Ermengilda D
ED
Van Riper
Gail
G
Egger
Linda
L
Kidambi
Usha
U
Mumford
Richard A
RA
Tong
Sharon
S
Tang
Wei
W
Colletti
Adria
A
Teffera
Yohannes
Y
Stearns
Ralph
R
MacCoss
Malcolm
M
Schmidt
John A
JA
Hagmann
William K
WK
D000577:Amides / Q000737:chemistry*; D000578:Amidines / Q000737:chemistry*; D019540:Area Under Curve; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*
D000577:Amides; D000578:Amidines; D039041:Integrin alpha4beta1