INHIBITING (ALPHA-V)(BETA-6) INTEGRIN

1 - 30 . (canceled)

31 . A compound of formula (I):

A-B—C  (I)

wherein:

A is

 wherein each R 1 is independently H, alkyl, halide, alkoxy, CF 3 , OH, alkylene-OH, NO 2 , —N(H)R a , or NH 2 ; wherein R a in A is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, or —(C 1 -C 6 )alkylene-O—C(O)O(C 1 -C 6 )alkyl;

B is alkylene, -alkylene-O—, or -alkylene-O-alkylene-;

C is

 wherein each R 3 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, aryl, hydroxyl, and alkoxy; and n with respect to R 3 is 0, 1, 2, 3, or 4;

R a in C is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, or —(C 1 -C 6 )alkylene-O—C(O)O(C 1 -C 6 )alkyl;

R 2 is

 and n in R 2 is 0, 1, 2, 3, or 4;

R 4 is independently selected from alkyl, —C(F 2 )CH 3 , cycloalkyl, heterocycloalkyl, -alkylene-cycloalkyl, —O-alkylene-cycloalkyl, —O-cycloalkyl, —O-alkyl, -alkylene-O-alkyl, -alkylene-O-cycloalkyl, and -alkylene-O-alkylene-cycloalkyl;

each R 5 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, aryl, hydroxyl, and alkoxy;

the absolute configuration at any stereocenter is R, S, or a mixture thereof;

or a pharmaceutically acceptable salt thereof;

provided that the compound is not selected from the group consisting of:

32 . The compound of claim 31 , wherein each R 1 is independently H, alkyl, halide, alkoxy, CF 3 , OH, alkylene-OH, —N(H)R a , or NH 2 ; and R a in C is H, (C 1 -C 6 )alkyl, or —(C 1 -C 6 )alkylene-O(C 1 -C 6 )alkyl; and R a in A is (C 1 -C 6 )alkyl, or —(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl.

33 . The compound of claim 32 , wherein each R 3 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, hydroxyl, and alkoxy; and n with respect to R 3 is 0 or 1.

34 . The compound of claim 33 , wherein each R 5 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, hydroxyl, and alkoxy.

35 . The compound of claim 34 , wherein R 4 is selected from the group consisting of:

36 . The compound of claim 31 , wherein:

a. each R 1 is independently H, alkyl, halide, or alkoxy;

b. each R 3 is independently selected from the group consisting of: halide, alkyl, and alkoxy; and n with respect to R 3 is 0 or 1; and

c. each R 5 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, hydroxyl, and alkoxy.

37 . The compound of claim 36 , wherein R 4 is independently selected from cycloalkyl, and heterocycloalkyl; and R a in C is H.

38 . The compound of claim 37 , wherein B is selected from the group consisting of:

q is 0, 1, 2, or 3; and p is 0, 1, or 2.

39 . The compound of claim 38 , wherein

a. each R 3 is independently selected from H, and F; and

b. each R a is H.

40 . The compound of claim 36 , wherein R 4 is selected from the group consisting of:

41 . The compound of claim 31 , wherein:

a. all instances of R 1 are H;

b. B is alkylene-O—;

c. each R 3 is independently selected from H, halide, alkyl and alkoxy; and n with respect to R 3 is 0 or 1;

d. R 4 is selected from cycloalkyl and heterocycloalkyl;

e. each R 5 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, hydroxyl, and alkoxy;

f. R a in C is H; and

the absolute configuration at any stereocenter is R, S, or a mixture thereof;

or a pharmaceutically acceptable salt thereof.

42 . The compound of claim 41 , wherein R 3 is independently selected from H and F.

43 . The compound of claim 41 , wherein B is

and q is 0, 1, 2, or 3.

44 . The compound of claim 43 , wherein:

a. q is 0, 1, or 2;

b. R 3 is H or F; and

c. each R 5 is independently selected from H, F, CF 3 , C(H)F 2 , C(F)H 2 , methyl, cyclopropyl, methylene-cyclopropyl, hydroxyl, and methoxy.

45 . A pharmaceutical composition formulated for oral delivery of an αvβ6 integrin inhibitor, the composition comprising the αvβ6 integrin inhibitor compound of claim 31 as an active compound and a pharmaceutically acceptable carrier formulated for oral therapeutic administration of the αvβ6 integrin inhibitor compound.

46 . A compound of formula (I):

A-B—C  (I)

wherein:

A is

 wherein each R 1 is independently H, alkyl, halide, alkoxy, CF 3 , OH, alkylene-OH, NO 2 , —N(H)R a , or NH 2 ; wherein R a in A is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, or —(C 1 -C 6 )alkylene-O—C(O)O(C 1 -C 6 )alkyl;

B is alkylene, -alkylene-O—, or -alkylene-O-alkylene-;

C is

 wherein each R 3 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, aryl, hydroxyl, and alkoxy; and n with respect to R 3 is 0, 1, 2, 3, or 4;

R a in C is H, (C 1 -C 6 )alkyl, —(C 1 -C 6 )alkylene-O—(C 1 -C 6 )alkyl, or —(C 1 -C 6 )alkylene-O—C(O)O(C 1 -C 6 )alkyl;

R 2 is

 and m in R 2 is 0, 1, 2, 3, or 4;

R 4 is independently selected from alkyl, —C(F 2 )CH 3 , cycloalkyl, heterocycloalkyl, -alkylene-cycloalkyl, —O-alkylene-cycloalkyl, —O-cycloalkyl, —O-alkyl, -alkylene-O-alkyl, -alkylene-O-cycloalkyl, and -alkylene-O-alkylene-cycloalkyl;

each R 5 is independently selected from H, halide, CF 3 , C(H)F 2 , C(F)H 2 , alkyl, cycloalkyl, -alkylene-alkoxy, aryl, hydroxyl, and alkoxy; and

the absolute configuration at any stereocenter is R, S, or a mixture thereof;

or a pharmaceutically acceptable salt thereof;

provided that the compound is not a compound of the formula:

47 . The compound of claim 46 , wherein

a. each R 1 is independently selected from the group consisting of: H, methyl, F, methoxy, CF 3 , OH, and alkylene-OH;

b. each R 3 in C is independently selected from H, halide, alkyl or alkoxy; and n with respect to R 3 is 0 or 1;

c. R a in C is H; and

d. each R 5 is independently selected from the group consisting of H, halide, cyclopropyl, methylene-cyclopropyl, and methoxy.

48 . The compound of claim 47 , wherein

a. B is selected from the group consisting of:

q is 0, 1, 2, or 3; and p is 0, 1, or 2; and

b. each R 1 is H.

49 . The compound of claim 48 , wherein

a. g is 0, 1, or 2; and p is 0 or 1;

b. n with respect to R 3 is 0;

C. R 4 is selected from the group consisting of: cycloalkyl and heterocycloalkyl; and

d. each R 5 is independently selected from the group consisting of H, F, cyclopropyl, methylene-cyclopropyl, and methoxy.

50 . A pharmaceutical composition formulated for oral delivery of an αvβ6 integrin inhibitor, the composition comprising the αvβ6 integrin inhibitor compound of claim 46 as an active compound and a pharmaceutically acceptable carrier formulated for oral therapeutic administration of the αvβ6 integrin inhibitor compound.