Synthesis of highly potent and selective hetaryl ureas as integrin alpha(V)beta3-receptor antagonists

Udo E W Lange; Gisela Backfisch; Jürgen Delzer; Hervé Geneste; Claudia Graef; Wilfried Hornberger; Andreas Kling; Arnulf Lauterbach; Thomas Subkowski; Christian Zechel

doi:10.1016/s0960-894x(02)00161-0

Synthesis of highly potent and selective hetaryl ureas as integrin alpha(V)beta3-receptor antagonists

Bioorg Med Chem Lett. 2002 May 20;12(10):1379-82. doi: 10.1016/s0960-894x(02)00161-0.

Authors

Udo E W Lange¹, Gisela Backfisch, Jürgen Delzer, Hervé Geneste, Claudia Graef, Wilfried Hornberger, Andreas Kling, Arnulf Lauterbach, Thomas Subkowski, Christian Zechel

Affiliation

¹ BASF AG, D-67056, Ludwigshafen, Germany. udo.lange@basf-ag.de

PMID: 11992781
DOI: 10.1016/s0960-894x(02)00161-0

Abstract

Solid-phase synthesis and SAR of integrin alpha(V)beta3-receptor antagonists containing a urea moiety as non-basic guanidine mimetic are described. The most potent compounds exhibited IC(50) values towards alpha(V)beta3 in the nanomolar range and high selectivity versus related integrins like alpha(IIb)beta3. For selected examples efficacy in functional cellular assays is demonstrated.

MeSH terms

Animals
CHO Cells
Cell Adhesion / drug effects*
Cricetinae
Drug Design
Humans
Models, Molecular
Molecular Conformation
Muscle, Smooth / drug effects
Muscle, Smooth / physiology
Receptors, Vitronectin / antagonists & inhibitors*
Structure-Activity Relationship
Urea / analogs & derivatives*
Urea / chemical synthesis*
Urea / pharmacology

Substances

Receptors, Vitronectin
Urea