N-aroylphenylalanine derivative VCAM-1 inhibitors

A compound of the formula:

• wherein:
• Z is hydrogen or lower alkyl, one of X and X′ is hydrogen, halogen, or lower alkyl, the other is a group of the formula:
• wherein:
• R1 is hydrogen or lower alkyl,
• R15 is halogen, nitro, lower alkyl sulfonyl, cyano, lower alkyl, OH, lower alkoxy, lower alkoxycarbonyl, carboxy, lower alkyl aminosulfonyl, perfluorolower alkyl, lower alkylthio, hydroxy lower alkyl, alkoxy lower alkyl, halo lower alkyl, alkylthio lower alkyl, alkylsulfinyl lower alkyl, alkylsufonyl lower alkyl, lower alkylsulfinyl, lower alkanoyl, aroy, aryloxy or a group of the formula R17—C≡C—,
• R16 is hydrogen, halogen, nitro, cyano, lower alkyl, OH, perfluoro lower alkyl, or lower alkylthio,
• R17 hydrogen, aryl, heteroaryl, or lower alkyl which is unsubstituted or substituted by OH, aryl, or heteroaryl;
• and
• a is 0 or 1;
• or one of X and X′ is a group of the formula:
• wherein
• Het is a 5- or 6-membered heteroaromatic ring wherein the heteroatoms of such ring consist of 1, 2, or 3 heteroatoms selected from N, O, and S;
• or
• Het is a 9- or 10-membered bicyclic heteroaromatic ring wherein the heteroatoms of such ring consist of 1, 2, 3 or 4 heteroatoms selected from O, S, and N,
• a, R1, R15 and R16 are as above, and
• R30 is hydrogen or lower alkyl, or is absent;
• or one of X and X′ is a group of the formula:
• wherein:
• R18 is hydrogen, lower alkyl, aryl, heteroaryl, arylalkyl, heteroaryl alkyl,
• R19 is lower alkyl, which is unsubstituted or substituted by one or more halogen, hydroxy, lower alkoxy, aryl, hetereoaryl, alkylthio, or R19 is aryl or heteroaryl, and
• R20 is lower alkyl or lower alkanoyl, or
• R19 and R20 taken together are tetramethylene;
• and
• Y is a group of the formula:
• wherein:
• R22 and R23 are independently hydrogen, lower alkyl, lower alkoxy, lower alkoxylalkyl, lower alkylamino, aryl, arylalkyl, nitro, cyano, lower alkylthio, lower alkylsulfinyl, lower alkyl sulfonyl, lower alkanoyl, halogen, or perfluoro lower alkyl and at least one of R22 and R23 is other than hydrogen, and
• R24 is hydrogen, hydroxy, lower alkyl, lower alkoxy, amino, aryl, nitro, cyano, lower alkyl sulfonyl, halogen, or is a group of the formula:
• wherein
• R25 is hydrogen, lower alkyl, aryl, aryl lower alkyl, alkoxy lower alkyl and R26 is hydrogen or lower alkyl, or
• R22 and R24 taken together are a fused benzene ring;
• or
• Y is a group Y-2 which is a five or six membered monocyclic heteroaromatic group wherein the heteroatoms of such group consist of 1, 2 or 3 heteroatoms selected from N, O, and S, or a 9- or 10-membered bicyclic heteroaromatic group wherein the heteroatoms of such group consist of 1, 2, 3 or 4 heteroatoms selected from O, S, and N, wherein said heteroaromatic group is bonded via a carbon atom to the amide carbonyl and one or two carbon atoms of said heteoaromatic group are substituted by lower alkyl, halogen, cyano, perfluoroalkyl, or aryl and at least one of said substituted carbon atoms is adjacent to the carbon atom bonded to the amide carbonyl;
• or the pharmaceutically acceptable salts or esters thereof.