Cell adhesion antagonists: synthesis and evaluation of a novel series of phenylalanine based inhibitors.
Several phenylalanine based inhibitors were synthesized as antagonists of the leukocyte cell adhesion process that is mediated through the interactions of the mucosal addressin cell adhesion molecule (MAdCAM) and the integrin alpha4beta7. Analogues 20, 21, 22 and 24 displayed inhibition of adhesion in a cell based assay in the low micromolar range.
Millennium Pharmaceutical, Cambridge, MA 02139, USA.
G C
GC
Harriman
C F
CF
Schwender
D
D
Gallant
N A
NA
Cochran
M J
MJ
Briskin
D002448:Cell Adhesion / Q000187:drug effects*; D015815:Cell Adhesion Molecules; D006801:Humans; D007136:Immunoglobulins / Q000502:physiology*; D016023:Integrins / Q000037:antagonists & inhibitors / Q000502:physiology*; D016393:Lymphoma, B-Cell; D015394:Molecular Structure; D009088:Mucoproteins / Q000502:physiology*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors / Q000502:physiology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016023:Integrins; C504265:MADCAM1 protein, human; D009088:Mucoproteins; D016201:Receptors, Lymphocyte Homing; C071777:integrin alpha4beta7; D010649:Phenylalanine