SUBSTITUTED BICYCLIC COMPOUNDS

摘要

The invention is directed to physiologically active compounds of general formula (I): wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring system containing at least one heteroatom selected from O, S or N; R<1> is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; R<2> is hydrogen, halogen, lower alkyl or lower alkoxy; Z<1> is NR<5>; L<1> is a -R<6>-R<7>- linkage (where R<6> is alkylene, alkenylene or alkynylene and R<7> is a direct bond, cycloalkylene, heterocycloalkylene, aryldiyl, heteroaryldiyl, -C(=Z<3>)-NR<5>-, -NR<5>-C(=Z<3>)-, -Z<3>-, -C(=O)-, -C(=NOR<5>)-, -NR<5>-, -NR<5>-C(=Z<3>)-NR<5>-, -SO2-NR<5>-, -NR<5>-SO2-, -O-C(=O)-, -C(=O)-O-, -NR<5>-C(=O)-O- or -O-C(=O)-NR<5>-); L<2> is an alkylene chain substituted by hydroxy, oxo, -OR<4>, -O-C(=O)-R<4>, -N(R<8>)-C(=O)-R<9>, -N(R<8>)-C(=O)-OR<9>, -N(R<8>)-SO2-R<9>, or -NY<3> Y<4>; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates of such compounds and their N-oxides and prodrugs. Such compounds have valuable pharmaceutical properties, in particular the ability to regulate the interaction of VCAM-1 and fibronectin with the integrin VLA-4 ( alpha 4 beta 1)