Discovery and evaluation of piperidinyl carboxylic acid derivatives as potent alpha(4)beta(1) integrin antagonists

G Müller; M Albers; R Fischer; G Hessler; T E Lehmann; H Okigami; M Tajimi; K Bacon; T Rölle

doi:10.1016/s0960-894x(01)00613-8

Discovery and evaluation of piperidinyl carboxylic acid derivatives as potent alpha(4)beta(1) integrin antagonists

Bioorg Med Chem Lett. 2001 Dec 3;11(23):3019-21. doi: 10.1016/s0960-894x(01)00613-8.

Authors

G Müller¹, M Albers, R Fischer, G Hessler, T E Lehmann, H Okigami, M Tajimi, K Bacon, T Rölle

Affiliation

¹ Bayer AG, Central Research, Building Q18, D-51368 Leverkusen, Germany.

PMID: 11714601
DOI: 10.1016/s0960-894x(01)00613-8

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.

MeSH terms

Area Under Curve
Carboxylic Acids / chemistry
Cell Adhesion / drug effects
Drug Design
Drug Evaluation, Preclinical
Humans
Inhibitory Concentration 50
Integrin alpha4beta1
Integrins / antagonists & inhibitors*
Integrins / metabolism
Jurkat Cells
Piperidines / chemistry*
Piperidines / metabolism
Piperidines / pharmacology*
Receptors, Lymphocyte Homing / antagonists & inhibitors*
Receptors, Lymphocyte Homing / metabolism
Structure-Activity Relationship
Vascular Cell Adhesion Molecule-1 / metabolism

Substances

Carboxylic Acids
Integrin alpha4beta1
Integrins
Piperidines
Receptors, Lymphocyte Homing
Vascular Cell Adhesion Molecule-1