N-Aroyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
A series of N-benzoyl-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine derivatives was prepared in order to optimize the substitution on the N-benzoyl moiety for VCAM/VLA-4 antagonist activity. Disubstitution in the 2- and 6-positions is favored and a range of small alkyl and halogen are tolerated. A model of the bioactive conformation of these compounds is proposed.
Sidduri
Achyutharao
A
Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. achyutharao.sidduri@roche.com
Tilley
Jefferson W
JW
Lou
Jian Ping
JP
Chen
Li
L
Kaplan
Gerry
G
Mennona
Frank
F
Campbell
Robert
R
Guthrie
Robert
R
Huang
Tai-Nan
TN
Rowan
Karen
K
Schwinge
Virginia
V
Renzetti
Louis M
LM
D006571:Heterocyclic Compounds / Q000737:chemistry; D006801:Humans; D006841:Hydrocarbons, Aromatic; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D018716:Molecular Mimicry; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011485:Protein Binding; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects*
D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D010649:Phenylalanine