N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists

Achyutharao Sidduri; Jefferson W Tilley; Kenneth Hull; Jian Ping Lou; Gerry Kaplan; Allen Sheffron; Li Chen; Robert Campbell; Robert Guthrie; Tai-Nan Huang; Nicholas Huby; Karen Rowan; Virginia Schwinge; Louis M Renzetti

doi:10.1016/s0960-894x(02)00386-4

N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists

Bioorg Med Chem Lett. 2002 Sep 2;12(17):2475-8. doi: 10.1016/s0960-894x(02)00386-4.

Authors

Achyutharao Sidduri¹, Jefferson W Tilley, Kenneth Hull, Jian Ping Lou, Gerry Kaplan, Allen Sheffron, Li Chen, Robert Campbell, Robert Guthrie, Tai-Nan Huang, Nicholas Huby, Karen Rowan, Virginia Schwinge, Louis M Renzetti

Affiliation

¹ Roche Research Center, Hoffmann-La Roche Inc., Nutley, NJ 07110, USA.

PMID: 12161161
DOI: 10.1016/s0960-894x(02)00386-4

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.

MeSH terms

Crystallography, X-Ray
Cycloparaffins / chemical synthesis
Cycloparaffins / pharmacology
Humans
Inhibitory Concentration 50
Integrin alpha4beta1 / antagonists & inhibitors*
Molecular Structure
Phenylalanine / analogs & derivatives*
Phenylalanine / pharmacology
Protein Binding
Structure-Activity Relationship
Vascular Cell Adhesion Molecule-1 / drug effects*

Substances

Cycloparaffins
Integrin alpha4beta1
Vascular Cell Adhesion Molecule-1
Phenylalanine