| 摘要 |
The invention is directed to physiologically active compounds of general formula (I) R1Z1-Het-L1-Ar1-L2-Y wherein Het is an optionally substituted, saturated, partially saturated or fully unsaturated 8 to 10 membered bicyclic ring containing at least one heteroatom selected from O, S or N; R1 is optionally substituted aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl or heterocycloalkyl; Z1 represents a direct bond, an alkylene chain, NR4, O or S(O)n; L1 is an a -R5-R6- linkage where R5 is alkylene, alkenylene or alkynylene and R6 is a direct bond, cycloalkylene, heterocycloalkylene, arylene, heteroaryldiyl, -C(=Z3)-NR4-,-NR4-C(=Z3)-, -Z3-, -C(=O)-, -C(=NOR4)-, -NR4-, -NR4-C(=Z3)-NR4-, -SO2-NR4-, -NR4-SO2-, -O-C(=O)-, -C(=O)-O-, -NR4-C(=O)-O- or -O-C(=O)-NR4-; L2 is a direct bond; an optionally substituted alkylene, alkenylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or arylene linkage; a -[C(=O)-N(R9)-C(R4)(R10)]P-linkage; a -Z4-R11- linkage; a -C(=O)-CH2-C(=O)-linkage; a -R11-Z4-R11- linkage; or a -L3-L4-L5- linkage; and Y is carboxy or an acid bioisostere; and the corresponding N-oxides, and their prodrugs; and pharmaceutically acceptable salts and solvates (e.g. hydrates) 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 (α4(1). |
