Discovery and evaluation of terephthalic acid derivatives as potent alpha4beta1 integrin antagonists.
Terephthalic acid based derivatives containing beta- and gamma-amino acid residues were prepared as antagonists of the leukocyte cell adhesion process that is mediated through the interaction of the very late antigen 4 (VLA-4) and the vascular cell adhesion molecule 1 (VCAM-1). The compounds 2, 10-12, 14, and 16-17 inhibited the adhesion in a cell based assay in the low and sub micromolar range.
Müller
Gerhard
G
Bayer AG, Central Research, Building Q18, D-51368 Leverkusen, Germany.
Albers
Markus
M
Hessler
Gerhard
G
Lehmann
Thomas E
TE
Okigami
Hiromi
H
Tajimi
Masaomi
M
Bacon
Kevin
K
Rölle
Thomas
T
D000577:Amides / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects*; D006801:Humans; D039041:Integrin alpha4beta1 / Q000037:antagonists & inhibitors*; D010795:Phthalic Acids / Q000737:chemistry / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry; D019010:Vascular Cell Adhesion Molecule-1 / Q000737:chemistry
D000577:Amides; D039041:Integrin alpha4beta1; D010795:Phthalic Acids; D019010:Vascular Cell Adhesion Molecule-1; C011363:terephthalic acid; D014508:Urea