title: N-Aroyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
abstract: 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.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA. achyutharao.sidduri@roche.com
authors.forename: Achyutharao
authors.initials: A
authors.lastname: Sidduri
authors.forename: Jefferson W
authors.initials: JW
authors.lastname: Tilley
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Lou
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Gerry
authors.initials: G
authors.lastname: Kaplan
authors.forename: Frank
authors.initials: F
authors.lastname: Mennona
authors.forename: Robert
authors.initials: R
authors.lastname: Campbell
authors.forename: Robert
authors.initials: R
authors.lastname: Guthrie
authors.forename: Tai-Nan
authors.initials: TN
authors.lastname: Huang
authors.forename: Karen
authors.initials: K
authors.lastname: Rowan
authors.forename: Virginia
authors.initials: V
authors.lastname: Schwinge
authors.forename: Louis M
authors.initials: LM
authors.lastname: Renzetti
mesh_terms: 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*
chemical_list: D006571:Heterocyclic Compounds; D006841:Hydrocarbons, Aromatic; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D010649:Phenylalanine