N-benzylpyroglutamyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
A series of N-(N-benzylpyroglutamyl)-4-substituted-L-phenylalanine derivatives was prepared as VLA-4/VCAM antagonists. Analogues substituted by electron deficient benzoylamino groups bearing bulky ortho substituents had low-nM potency in an ELISA assay and low-microM activity in a cell based assay.
Chen
L
L
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Tilley
J W
JW
Guthrie
R W
RW
Mennona
F
F
Huang
T N
TN
Kaplan
G
G
Trilles
R
R
Miklowski
D
D
Huby
N
N
Schwinge
V
V
Wolitzky
B
B
Rowan
K
K
D002460:Cell Line; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects*
D039041:Integrin alpha4beta1; D016023:Integrins; D016201:Receptors, Lymphocyte Homing; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1; D010649:Phenylalanine