Aminoaryl-integrin agonists compounds

A method comprising contacting integrin expressing cells with a VLA-4 integrin agonist having formula (I):

• wherein, R1 is hydrogen, lower alkyl, or aryl;
• Ar is aryl, provided that when Ar1 and R1 are both phenyl, the 2 and 6 positions of each ring are substituted with hydrogen;
• T is aryl;
• X is a 1-20 atom linking chain containing any combination of —CH2—, —C(O)—, —C(O)NR2—, —NR2—, —C(O)O— and —O—, each of which may independently be absent or present one or more times;
• provided that when X contains —C(O)N(R2)—, and —C(O)N(R2)— directly attaches to T, then R2 is hydrogen;
• Y is selected from a group consisting essentially of hydrogen, (C1-C4)alkyl, aryl, cycloalkyl, N,N-dialkylamino, heterocyclyl, N,N-di(aralkyl)aminoaryl, (N-aralkyl)(N-alkyl)aminoaryl and a combination thereof, Ar1 and R1 may each be independently substituted or multiply substituted and selected at each occurrence from the group consisting essentially of lower alkyl, alkoxy, hydroxyalkyl, —OH, alkoxyalkyl, (C1-C3 alkyl)2amino, alkoxyalkoxy, cycloalkyl, cycloalkylalkyl, aryl, heterocyclyl, alkylaryl, aralkyl, alkylheterocyclyl, and heterocyclylalkyl, groups;
• Y may be unsubstituted or substituted with one or more substituents selected from the group consisting essentially of halogen, lower alkyl, alkoxy, hydroxyalkyl, aliphatic acyl, —CF3, oxo, —CN, —OH, alkoxyalkyl, (C1-C3 alkyl)2amino, alkoxyalkoxy, cycloalkyl, cycloalkylalkyl, aryl, heterocyclyl, alkylaryl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, and aryloxyalkyl groups;
• T may be unsubstituted or substituted with one or more substituents selected from the group consisting essentially of lower alkyl, alkoxy, hydroxyalkyl, aliphatic acyl, —CN, —OH, halogen, heterocycloyl, alkoxyalkyl, (C1-C3 alkyl)2amino, alkoxyalkoxy, cycloalkyl, cycloalkylalkyl, heterocyclyl, alkylheterocyclyl, heterocyclylalkyl and a combination thereof, provided that when T is thiazolyl group and X and Y taken together form a C1-C8 alkyl group, then the 5-position of said thiazole ring is unsubstituted;
• substituents of T may be taken together with up to two atoms of X to form ring;
• and R2 when present, may be selected independently and at each occurrence from the groups consisting essentially of:
• hydrogen, lower alkyl, acetyl and methanesulfonyl.

A complex formed between (i) an integrin expressing cell and a integrin agonist;

• and/or (ii) an integrin binding protein wherein the integrin agonist has general formula (I)
• wherein, R1 is hydrogen, lower alkyl, or aryl;
• Ar is aryl, provided that when Ar1 and R1 are both phenyl, the 2 and 6 positions of each ring are substituted with hydrogen;
• T is aryl;
• X is a 1-20 atom linking chain containing any combination of —CH2—, —C(O)—, —C(O)NR2—, —NR2—, —C(O)O— and —O—, each of which may independently be absent or present one or more times;
• provided that when X contains —C(O)N(R2)—, and —C(O)N(R2)— directly attaches to T, then R2 is hydrogen;
• Y is selected from a group consisting essentially of hydrogen, (C1-C4)alkyl, aryl, cycloalkyl, N,N-dialkylamino, heterocyclyl, N,N-di(aralkyl)aminoaryl, (N-aralkyl)(N-alkyl)aminoaryl and a combination thereof, Ar1 and R1 may each be independently substituted or multiply substituted and selected at each occurrence from the group consisting essentially of lower alkyl, alkoxy, hydroxyalkyl, —OH, alkoxyalkyl, (C1-C3 alkyl)2amino, alkoxyalkoxy, cycloalkyl, cycloalkylalkyl, aryl, heterocyclyl, alkylaryl, aralkyl, alkylheterocyclyl, and heterocyclylalkyl, groups;
• Y may be unsubstituted or substituted with one or more substituents selected from the group consisting essentially of halogen, lower alkyl, alkoxy, hydroxyalkyl, aliphatic acyl, —CF3, oxo, —CN, —OH, alkoxyalkyl, (C1-C3 alkyl)2amino, alkoxyalkoxy, cycloalkyl, cycloalkylalkyl, aryl, heterocyclyl, alkylaryl, aralkyl, alkylheterocyclyl, heterocyclylalkyl, and aryloxyalkyl groups;
• T may be unsubstituted or substituted with one or more substituents selected from the group consisting essentially of lower alkyl, alkoxy, hydroxyalkyl, aliphatic acyl, —CN, —OH, halogen, heterocycloyl, alkoxyalkyl, (C1-C3 alkyl)2amino, alkoxyalkoxy, cycloalkyl, cycloalkylalkyl, heterocyclyl, alkylheterocyclyl, heterocyclylalkyl and a combination thereof, provided that when T is thiazolyl group and X and Y taken together form a C1-C8 alkyl group, then the 5-position of said thiazole ring is unsubstituted;
• substituents of T may be taken together with up to two atoms of X to form ring;
• and R2 when present, may be selected independently and at each occurrence from the groups consisting essentially of:
• hydrogen, lower alkyl, acetyl and methanesulfonyl.