Inhibitors of α4 mediated cell adhesion

N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;

• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(piperidinomethyl)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-[(4-methylpiperazinyl)amino]phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(morpholinomethyl)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(N,N-dimethylamino)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(N,N-dimethylcarbamoyl)phenyl]-L-phenylalanine;
• N-(2,6-dichloro-4-hydroxybenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2-ethoxy-6-methoxyphenyl)-L-phenylalanine;
• N-(2,6-difluorobenzoyl)-4-(2-6,dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2,3-methylenedioxy-6-methoxyphenyl)-L-phenylalanine;
• -
• N-(2,6-dichlorobenzoyl)-3-(1-hydroxyethy)-4-(2,6dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2,4,6-trimethoxyphenyl)-L-phenylalanine;
• N-[2,6-dichloro-4-[(trifluoromethanesulfonyl)amino]benzoyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• or
• N-[2,6-dichloro-4-[(2-thienylsulfonyl)amino]benzoyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• or a lower alkyl ester thereof;
• or pharmaceutically acceptable salt thereof.

The pharmaceutical composition comprising a therapeutically effective amount of:

• N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(1-piperidinomethyl)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-[(4-methylpiperazinyl)amino]phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(morpholinomethyl)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(N,N-dimethylamino)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(N,N-dimethylcarbamoyl)phenyl]-L-phenylalanine;
• N-(2,6-dichloro-4-hydroxybenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2-ethoxy-6-methoxyphenyl)-L-phenylalanine;
• N-(2,6-difluorobenzoyl)-4-(2-6,dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2,3-methylenedioxy-6-methoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-3-(1-hydroxyethy)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2,4,6-trimethoxyphenyl)-L-phenylalanine;
• N-[2,6-dichloro-4-[(trifluoromethanesulfonyl)amino]benzoyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• or -
• N-[2,6-dichloro-4-[(2-thienylsulfonyl)amino]benzoyl]4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• or a lower alkyl ester thereof;
• or a pharmaceutically acceptable salt thereof;
• and a pharmaceutically acceptable carrier or diluent.

A method for inhibiting the adhesion of a cell expressing an α4 integrin to MAdCAM-1, VCAM-1 or CS-1, which comprises

• administering to a patient in need of such treatment an inhibitory amount of:
• N-(2,6-dichlorobenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(piperidinomethyl)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-[(4-methylpiperazinyl)amino]phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(morpholinomethyl)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(N,N-dimethylamino)phenyl]-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-[2,6-dimethoxy-4-(N,N-dimethylcarbamoyl)phenyl]-L-phenylalanine;
• N-(2,6-dichloro-4-hydroxybenzoyl)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2-ethoxy-6-methoxyphenyl)-L-phenylalanine;
• N-(2,6-difluorobenzoyl)-4-(2-6,dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2,3-methylenedioxy-6-methoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-3-(1-hydroxyethy)-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• N-(2,6-dichlorobenzoyl)-4-(2,4,6-trimethoxyphenyl)-L-phenylalanine;
• N-[2,6-dichloro-4-[(trifluoromethanesulfonyl)amino]benzoyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• or
• N-[2,6-dichloro-4-[(2-thienylsulfonyl)amino]benzoyl]-4-(2,6-dimethoxyphenyl)-L-phenylalanine;
• or a lower ester thereof;
• or pharmaceutically acceptable salt thereof.