Dihydro-benzo(1,4)oxazines

摘要

The invention is directed to physiologically active compounds of formula (I):whereinR<1 represents R<3-Z<3-, R<3-L<2-R<4-Z<3-, R<3-L<3-Ar<1-L<4-Z<3- or R<3-L<3-Ar<1-L<2-R<4-Z<3-;R<2 represents hydrogen, halogen, lower alkyl or lower alkoxy;A<1 represents a straight chain C2-3alkylene linkage optionally substituted by one or more groups chosen from alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, imino, oxo, thioxo, or alkyl substituted by -ZR<6, -NY<1Y<2, -CO2R<6 or -C(=O)-NY<1Y<2;L<1 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)mR<9, R<3, -C(=O)-R<3, -C(=O)-OR<3, -N(R<8)-C(=O)-R<9, -N(R<8)-C(=O)-OR<9, -N(R<8)-SO2-R<9, -NY<4Y<5 or -[C(=O)-N(R<10)-C(R<5)(R<11)]p-C(=O)-NY<4Y<5, or by (b) alkyl substituted by an acidic functional group, or by S(O)mR<9, -C(=O)-NY<4Y<5 or -NY<4Y<5; a -[C(=O)-N(R<10)-C(R<5)(R<11)]p- linkage; a -Z<2-R<12- linkage; a -C(=O)-CH2-C(=O)- linkage; a -R <12-Z<2-R<12- linkage; a -C(R<4)(R<13)-[C(=O)-N(R<10)-C(R<5)(R<11)]p- linkage; or a -L<5-L<6-L<7- linkage;Z<1 is NR<17 or O;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 (alpha4beta1).