PYRIDINONE ANTAGONISTS OF ALPHA-4 INTEGRINS

1 .- 19 . (canceled)

20 . A pharmaceutical composition comprising a compound of claim 29 and a pharmaceutically acceptable carrier.

21 . A method of treating an inflammatory disease comprising administering to a mammalian subject in need thereof a pharmaceutically effective amount of a compound according to claim 29 , wherein the inflammatory disease is selected from the group consisting of asthma, inflammatory bowel disease, ulcerative colitis, Crohn's disease, multiple sclerosis, rheumatoid arthritis, tumor metastasis, graft versus host disease, and organ or tissue rejection.

22 . The method of claim 21 , wherein said inflammatory disease is a member selected from Crohn's disease and ulcerative colitis.

23 . An in vitro assay for measuring binding of an α4β1 or α4β7 integrin to an integrin ligand,

wherein the assay comprises:

(i) binding the ligand to a surface;

(ii) contacting the ligand with a cell expressing the integrin, in the presence of a compound of claim 29 ; and

(iii) measuring the amount of cells bound to the surface.

24 . The assay according to claim 23 , wherein the integrin ligand is a member selected from fibronectin (FN), VCAM-1, osteopontin and MadCAM.

25 . (canceled)

26 . An in vitro assay for measuring binding of the compound to an α4β1 or α4β7 integrin in the presence of a candidate molecule, wherein the assay comprises incubating the test molecule in the presence of a compound of claim 29 labeled with a radioactive, colorimetric or fluorescent label, and measuring the amount of the labeled compound for binding to the integrin.

27 . An in vitro assay for identifying a candidate molecule capable of binding to α4β1 or α4β7 integrin, wherein the assay comprises incubating the candidate molecule in the presence of a compound of claim 29 labeled with a radioactive, colorimetric or fluorescent label, and measuring the amount of the labeled compound for binding to the integrin, and wherein the candidate molecule is identified as capable of binding to the integrin if it exhibits a binding activity of an IC 50 of not more than 10 μM in the assay.

28 . (canceled)

29 . A compound of Formula (Ia′), Formula (Ib), or Formula (Ic)

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof,

wherein

m is an integer selected from 0 to 4;

n is an integer selected from 0 to 3;

p is an integer selected from 0 to 4;

m1 is an integer selected from 0 to 3;

ring A is a member selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

Cy is a member selected from substituted or unsubstituted (C 3 -C 10 )cycloalkyl, substituted or unsubstituted 3- to 10-membered heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl;

E is selected from O, S, C(O), S(O) 2 and NR 40 , wherein R 40 is a member selected from substituted or unsubstituted alkyl;

each R 1 , each R 2 , R 1a and R 1b are a member independently selected from H, substituted or unsubstituted (C 1 -C 10 )alkyl, substituted or unsubstituted 2- to 10-membered heteroalkyl, substituted or unsubstituted (C 3 -C 10 )cycloalkyl, substituted or unsubstituted 3- to 10-membered heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, nitro, CN, halogen, OR 12 , SR 12 , NR 12 R 13 , C(O)R 14 , C(O)NR 12 R 13 , OC(O)NR 12 R 13 , C(O)OR 12 , NR 15 C(O)R 14 , NR 15 C(O)OR 12 , NR 15 C(O)NR 12 R 13 , NR 15 C(S)NR 12 R 13 , NR 15 S(O) 2 R 14 , S(O) 2 NR 12 R 13 and S(O) z R 14 ,

wherein

z is 1 or 2;

R 12 , R 13 and R 15 are members independently selected from H, acyl, substituted or unsubstituted (C 1 -C 10 )alkyl, substituted or unsubstituted 2- to 10-membered heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted (C 3 -C 10 )cycloalkyl, substituted or unsubstituted 3- to 10-membered heterocycloalkyl; and

R 14 is a member independently selected from substituted or unsubstituted (C 1 -C 10 )alkyl, substituted or unsubstituted 2- to 10-membered heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted (C 3 -C 10 )cycloalkyl, substituted or unsubstituted 3- to 10-membered heterocycloalkyl,

wherein R 12 and R 13 , together with the nitrogen atoms to which they are attached, are optionally joined to form a 4- to 7-membered ring, and

wherein two adjacent R 1 , together with the atoms to which they are attached, are optionally joined to form a 5- to 7-membered ring, and

wherein two adjacent R 2 , together with the atoms to which they are attached, are optionally joined to form a 5- to 7-membered ring;

R 3 , R 4 and R 5 are members independently selected from H, substituted or unsubstituted (C 1 -C 4 )alkyl, halogen and CN; and

R 6 is a member selected from H and substituted or unsubstituted (C 1 -C 4 )alkyl.

30 . The compound of claim 29 , wherein the compound is of Formula (Ia′):

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof.

31 . The compound of claim 29 , wherein the compound is of Formula (IIa′):

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof, wherein m, n, p, Cy, A, R 1 , and R 2 are as defined in claim 29 .

32 . The compound of claim 29 , wherein the compound is of Formula (IIIa′):

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof, wherein X 1 , X 2 , X 3 and X 4 are members independently selected from N and CR 2 , q is an integer selected from 0 to 4, and m, Cy, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are as defined in claim 29 .

33 . The compound of claim 29 , wherein the compound is of Formula (Ib):

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof.

34 . The compound of claim 29 , wherein the compound is of Formula (IIb):

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof, wherein Cy, R 1a , A, R 2 and p are as defined in claim 29 .

35 . The compound of claim 29 , wherein the compound is of Formula (Ic):

or a salt or solvate or single stereoisomer or mixture of stereoisomers thereof.

36 . The compound of claim 29 , wherein ring A is a member selected from substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted thiazole, substituted or unsubstituted imidazolyl and substituted or unsubstituted thiophene.

37 . The compound of claim 29 , wherein R 1a and R 1b are H.

38 . The compound of claim 29 , wherein R 3 , R 4 and R 5 are each independently selected from H and F.

39 . The compound of claim 29 , wherein n is 1 or 2, m is 0 or 1, and p is 0 or 1.

40 . The compound of claim 29 , wherein R 6 is H.

41 . The compound of claim 29 , wherein Cy is a member selected from substituted or unsubstituted phenyl and substituted or unsubstituted pyridyl.

42 . A compound selected from FIG. 2 , or a salt or a solvate thereof.