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Abstract

The invention is directed to physiologically active compounds of formula (I): ##STR1## wherein R.sup.1 represents R.sup.3 --Z.sup.3 --, R.sup.3 --L.sup.2 --R.sup.4 --Z.sup.3 --, R.sup.3 --L.sup.3 --Ar.sup.1 --L.sup.4 --Z.sup.3 -- or R.sup.3 --L.sup.3 --Ar.sup.1 --L.sup.2 --R.sup.4 --Z.sup.3 --; R.sup.2 represents hydrogen, halogen, lower alkyl or lower alkoxy; A.sup.1 represents a straight chain C.sub.2-3 alkylene linkage optionally substituted by one or more groups chosen from alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, imino, oxo, thioxo, or alkyl substituted by --ZR.sup.6, --NY.sup.1 Y.sup.2, --CO.sub.2 R.sup.6 or --C(.dbd.O)--NY.sup.1 Y.sup.2 ; L.sup.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).sub.m R.sup.9, R.sup.3, --C(.dbd.O)--R.sup.3, --C(.dbd.O)--OR.sup.3, --N(R.sup.8)--C(.dbd.O)--R.sup.9, --N(R.sup.8)--C(.dbd.O)--OR.sup.9, --N(R.sup.8)--SO.sub.2 --R.sup.9, --NY.sup.4 Y.sup.5 or --[C(.dbd.O)--N(R.sup.10)--C(R.sup.5)(R.sup.11)].sub.p --C(.dbd.O)--NY.sup.4 Y.sup.5, or by (b) alkyl substituted by an acidic functional group, or by S(O).sub.m R.sup.9, --C(.dbd.O)--NY.sup.4 Y.sup.5 or --NY.sup.4 Y.sup.5 ; a --[C(.dbd.O)--N(R.sup.10)--C(R.sup.5)(R.sup.11)].sub.p -- linkage; a --Z.sup.2 --R.sup.12 -- linkage; a --C(.dbd.O)--CH.sub.2 --C(.dbd.O)--linkage; a --R .sup.12 --Z.sup.2 --R.sup.12 -- linkage; a --C(R.sup.4)(R.sup.13)--[C(.dbd.O)--N(R.sup.10)--C(R.sup.5)(R.sup.11)]. sub.p -- linkage; or a --L.sup.5 --L.sup.6 --L.sup.7 -- linkage; Z.sup.1 is NR.sup.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 (.alpha.4.beta.1).

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First Claim