title: Discovery and evaluation of piperidinyl carboxylic acid derivatives as potent alpha(4)beta(1) integrin antagonists.
abstract: Piperidinyl carboxylic acid-based derivatives were prepared as antagonists of the leukocyte cell adhesion process that is mediated through the interaction of the alpha(4)beta(1) integrin (VLA-4, very late antigen 4) and the vascular cell adhesion molecule 1 (VCAM-1). Compounds 2a-h inhibited the adhesion in a cell-based assay in the low and sub micromolar range, a pharmacokinetic study of 2d is reported.
authors.affiliation: Bayer AG, Central Research, Building Q18, D-51368 Leverkusen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Müller
authors.forename: M
authors.initials: M
authors.lastname: Albers
authors.forename: R
authors.initials: R
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: Hessler
authors.forename: T E
authors.initials: TE
authors.lastname: Lehmann
authors.forename: H
authors.initials: H
authors.lastname: Okigami
authors.forename: M
authors.initials: M
authors.lastname: Tajimi
authors.forename: K
authors.initials: K
authors.lastname: Bacon
authors.forename: T
authors.initials: T
authors.lastname: Rölle
mesh_terms: D019540:Area Under Curve; D002264:Carboxylic Acids / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D039041:Integrin alpha4beta1; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019169:Jurkat Cells; D010880:Piperidines / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D002264:Carboxylic Acids; D039041:Integrin alpha4beta1; D016023:Integrins; D010880:Piperidines; D016201:Receptors, Lymphocyte Homing; D019010:Vascular Cell Adhesion Molecule-1