EP1392306B1 — Substituted tetrahydroisoquinolines for use in the treatment of inflammatory diseases

USPTO Abstract

The invention is directed to physiologically active compounds of formula (I): wherein: R<SUP>1 </SUP>represents optionally substituted aryl, optionally substituted heteroaryl, R<SUP>3</SUP>NH-Ar<SUP>1</SUP>-L<SUP>2</SUP>- or R<SUP>3</SUP>-NH-C(-O)-NH-Ar<SUP>2</SUP>-L<SUP>2</SUP>-; R<SUP>3 </SUP>represents aryl or heteroaryl; Ar<SUP>1 </SUP>represents a saturated, partially saturated or fully unsaturated 8- to 10-membered bicyclic ring system containing at least one heteroatom selected from O, S or N; Ar<SUP>2 </SUP>represents aryldiyl or heteroaryldiyl; L<SUP>1 </SUP>represents a linkage, such as an alkylene linkage; L<SUP>2 </SUP>represents an alkylene chain linkage; R<SUP>2 </SUP>represents hydrogen, halogen, C<SUB>1-4</SUB>alkyl or C<SUB>1-4</SUB>alkoxy; and Y is carboxy or an acid bioisostere; but excluding compounds where an oxygen, nitrogen or sulfur atom is attached directly to a carbon carbon multiple bond of an alkenylene or alkynylene residue; and the corresponding N-oxides and ester prodrugs thereof, and the pharmaceutically acceptable salts and solvates of such compounds, and the N-oxides and ester prodrugs thereof. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 (alpha4beta1).