N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
A systematic structure-activity relationship investigation of the lead compound 1 resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation.
Sidduri
Achyutharao
A
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
Tilley
Jefferson W
JW
Hull
Kenneth
K
Lou
Jian Ping
JP
Kaplan
Gerry
G
Sheffron
Allen
A
Chen
Li
L
Campbell
Robert
R
Guthrie
Robert
R
Huang
Tai-Nan
TN
Huby
Nicholas
N
Rowan
Karen
K
Schwinge
Virginia
V
Renzetti
Louis M
LM
D018360:Crystallography, X-Ray; D003516:Cycloparaffins / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects*
D003516:Cycloparaffins; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D010649:Phenylalanine