UREAS AND THEIR USE AS CELL ADHESION MODULATORS

摘要

The invention is directed to physiologically active compounds of general formula (I): wherein R1 is lower alkyl, R2 is aryl, arylalkyl, heteroaryl or heteroarylalkyl, or R?1 and R2¿ together with the nitrogen atom to which they are attached form a cyclic amine, Ar1 is aryldiyl or heteroaryldiyl, Ar2 is optionally substituted phenylene or heteroaryldiyl, 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(=Z?1)-NR4-, -NR4-C(=Z1)-, -Z1¿-, -C(=O)-, -C(=NOR?4)-, -NR4-, -NR4-C(=Z1)-NR4¿-, -SO¿2?-NR?4-, -NR4-SO¿2-, -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 aryldiyl linkage, a -[C(=O)-N(R?9)-C(R4)(R10)]¿p-linkage, a-Z3-R11-linkage, a -C(=O)-CH¿2?-C(=O)- linkage or a -R?11-Z3-R11¿- 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 (α4β1).