Inhibitors of (α-v)(β-6) integrin
Disclosed are small molecule inhibitors of αvβ6 integrin, and methods of using them to treat a number of specific diseases or conditions.
1. A compound represented by formula (I):
A-B-C (I)
wherein:
A is
B is -alkylene-C(O)N(R)—;
C is
R is H, alkyl, or aryl;
R 1 is independently H, alkyl, halide, alkoxy, CF 3 , OH, NO 2 , —N(H)R, or NH 2 ;
R 2 is H, alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, alkoxy, —OH, N(R)C(O)R 4 , or —N(R)-heteroaryl;
R 3 is independently alkyl, halide, alkoxy, CF 3 , OH, NO 2 , or NH 2 ;
R 4 is alkyl, cylcoalkyl, heterocycloalkyl, aryl, heteroaryl, -alkylene-heterocyclyl, -alkylene-N(R)C(O)R 5 , or -alkylene-N(R)—SO 2 Me;
R 5 is alkyl, or cycloalkyl;
R 6 is H, or alkyl;
X is C(R c );
R c is H, alkyl, aryl, OH, or halide;
R d is H, or (C 1 -C 6 )alkyl;
a is independently 0, or 1; and
b is 0, 1, 2, 3, or 4;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein R is H or Me.
3. The compound of claim 1 , wherein at least one instance of R 1 is alkyl, halide, alkoxy, CF 3 , OH, —N(H)R, or NH 2 .
4. The compound of claim 3 , wherein R 1 is alkyl, or halide.
5. The compound of claim 2 , wherein
A is
6. The compound of claim 5 , wherein R c is H.
7. The compound of claim 6 , wherein R d is H.
8. The compound of claim 7 , wherein at least one instance of a is 0.
9. The compound of claim 7 , wherein at least one instance of a is 1.
10. The compound of claim 7 , wherein b is 0, 1 or 2.
11. The compound of claim 10 , wherein R 3 is independently alkyl, halide, alkoxy, or NH 2 .
12. The compound of claim 10 , wherein R 6 is H.
13. The compound of claim 1 , wherein R 2 is H, alkyl, aryl, heteroaryl, hydroxyl, or alkoxy.
14. The compound of claim 13 , wherein R 2 is substituted or unsubstituted phenyl.
15. The compound of claims 1 , wherein R 2 is —N(H)-2-pyridinyl, or —N(H)-2,4-pyrimidinyl.
16. The compound of claim 1 , wherein R 2 is —N(H)C(O)Me.
17. The compound of claim 1 , wherein
R 4 is Me,
and
Y is H, F, or Cl.
18. The compound of claim 1 , wherein R 2 is —N(R)C(O)R 4 .
19. The compound of claim 18 , wherein R is CH 3 ; and R 4 is CH 3 .
20. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.