title: N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.
abstract: 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.
authors.affiliation: Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.
authors.forename: Achyutharao
authors.initials: A
authors.lastname: Sidduri
authors.forename: Jefferson W
authors.initials: JW
authors.lastname: Tilley
authors.forename: Kenneth
authors.initials: K
authors.lastname: Hull
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Lou
authors.forename: Gerry
authors.initials: G
authors.lastname: Kaplan
authors.forename: Allen
authors.initials: A
authors.lastname: Sheffron
authors.forename: Li
authors.initials: L
authors.lastname: Chen
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: Nicholas
authors.initials: N
authors.lastname: Huby
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: 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*
chemical_list: D003516:Cycloparaffins; D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D010649:Phenylalanine