Focused library approach for identification of new N-acylphenylalanines as VCAM/VLA-4 antagonists.
A structure-based focused library approach was employed in an effort to identify more lipophilic replacements for the N-benzylpyroglutamyl group of the VCAM/VLA-4 antagonist 2. This effort led to the discovery of two new classes of potent antagonists characterized by the N-(alpha-phenylcyclopentanoyl- and the N-(2,6-dimethylbenzoyl)-derivatives 60 and 64.
Chen
Li
L
Roche Research Center, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA. li.chen@roche.com
Trilles
Richard
R
Miklowski
Dorota
D
Huang
Tai-Nan
TN
Fry
David
D
Campbell
Robert
R
Rowan
Karen
K
Schwinge
Virginia
V
Tilley
Jefferson W
JW
D002460:Cell Line; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D015394:Molecular Structure; D010649:Phenylalanine / Q000737:chemistry / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000187:drug effects*
D039041:Integrin alpha4beta1; D019010:Vascular Cell Adhesion Molecule-1; D010649:Phenylalanine