| 摘要 |
The invention is directed to physiologically active compounds of formula (I) wherein R1 represents R3-Z3-, R3-L2-R4-Z3-, R3-L3-Ar1-L4-Z3- or R3-L3-Ar1-L2 - R4-Z3-; R2 represents hydrogen, halogen, lower alkyl or lower alkoxy; A1 represents a straight chain C1-3alkylene linkage optionally substituted by o ne or more groups chosen from alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, imino, oxo, thioxo, or alkyl substituted by -ZR6, -NY1Y2, - CO2R6 or -C(=O)-NY1Y2; L1 represents a direct bond; an alkenylene, alkylene, alkynylene, cycloalkenylene, cycloalkylene, heteroaryldiyl, heterocycloalkylene or arylene linkage each optionally substituted by (a) an acidic functional group, cyano, oxo, -S(O)mR9, R3, -C(=O)-R3, -C(=O)-OR3, - N(R8)-C(=O)-R9, -N(R8)-C(=O)-OR9, -N(R8)-SO2-R9, -NY4Y5 or -[C(=O)-N(R10)- C(R5)(R11)]p-C(=O)-NY4Y5, or by (b) alkyl substituted by an acidic functiona l group, or by S(O)mR9, -C(=O)-NY4Y5 or -NY4Y5; a -[C(=O)-N(R10)-C(R5)(R11)]p- linkage; a -Z2-R12- linkage; a -C(=O)-CH2-C(=O)- linkage; a -R12-Z2-R12- linkage; a -C(R4)(R13)-[C(=O)-N(R10)-C(R5)(R11)]p- linkage; or a -L5-L6-L7- linkage; Z1 is C(R7)(R7a), C(=O) or CH(OH); 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).
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