Prostaglandin transporter inhibitors and uses thereof
View Patent ↗Disclosed are compounds for inhibiting prostaglandin transporter (PGT) activity, pharmaceuticals compositions including the compounds, and methods of treating subjects using the compounds.
1. A compound having the structure:
wherein W is O or NR5;
R4 and R5 are independently H or —CH 3 ;
R6 is O or NR9;
R7 is H, —CH 3 , —C(CH 3 ) 3 , —CH 2 OH, —(CH 2 ) 2 OH, —(CH 2 ) 2 O(CH 2 ) 2 OH, —(CH 2 CH 2 O) 3 CH 3 , —(CH 2 CH 2 O) 2 CH 2 CO 2 CH 3 , —(CH 2 ) 5 CH 3 ,
R8 is H, —OH, —CH 2 OH, —CO 2 H, —CO 2 CH 2 CH 3 , —CO(CH 2 ) 6 CH 3 , —OCH 3 , —NH 2 , —SO 2 NH 2 , —CONH-Bn or
R9 is H or —CH 3 ;
R10 is —CH 2 NH 2 , —CO 2 H or —CO 2 CH 3 ;
R11 is —SO 2 -Ph, —CH 2 -Ph, —CONH-Ph, —COCH 3 ,
and
R12 is —CH 3 ,
where X1, X2, X3, X4, X5 and X6 are independently H, halogen, —OH, —CH 3 , —CF 3 , —OCH 3 , —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 H or —CH 2 CO 2 CH 3 ;
where X7 is independently H, halogen, —OH, —CH 3 , —CF 3 , —OCH 3 , —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 H, —CH 2 CO 2 CH 3 , phenyl or —O-Bn; and
where a=1-2; b=1-5; c=0-1; d=4-7; and e=0-1;
or a pharmaceutically acceptable salt thereof.
2. The compound of claim 1 , wherein W is NR5.
3. The compound of claim 1 , wherein R6 is NR9.
4. The compound of claim 1 , wherein at least one of R4, R5 and R9 is H.
5. The compound of claim 1 , wherein all of R4, R5 and R9 are H.
6. The compound of claim 1 , wherein R8 is located in para position.
7. The compound of claim 1 , wherein one of X1 and X2 is H, and the other is halogen, —CF 3 , —CH 3 , —CO 2 H, —CO 2 CH 3 , —OCH 3 or phenyl.
8. The compound of claim 1 , wherein both X1 and X2 are halogen.
9. The compound of claim 1 , wherein one of X3 and X4 is H, and the other is halogen, —CO 2 H, —CO 2 CH 3 , —CH 2 CO 2 H, —CH 2 CO 2 CH 3 , —OH, —OCH 3 or —O-Bn.
10. The compound of claim 1 , wherein one of X3 and X4 is —OH, and the other is halogen, —CO 2 H or —CO 2 CH 3 .
11. The compound of claim 1 , wherein one of X5 and X6 is H, and the other is halogen, —CF 3 , —OCH 3 or phenyl.
12. The compound of claim 1 , wherein both X5 and X6 are halogen.
13. The compound of claim 1 , wherein X7 is H, —CF 3 or —OCH 3 .
14. The compound of claim 1 , wherein one or both of X1 and X2 are located in ortho position.
15. The compound of claim 1 , wherein one or both of X1 and X2 are located in meta position.
16. The compound of claim 1 , wherein X1 is located in meta position and X2 is located in para position.
17. The compound of claim 1 , wherein X1 is located in ortho position and X2 is located in para position.
18. The compound of claim 1 , wherein X3 is in meta position and X4 is in para position.
19. The compound of claim 1 , wherein X5 or X6 is in meta position.
20. The compound of claim 1 , wherein X5 or X6 is in para position.
21. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
22. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
23. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
24. The compound of claim 1 , wherein
R1 is
R2 is
and
R3 is
and
where X1 is H or halogen;
where X4 is H, halogen or —CO 2 H; and
where X5 is H, halogen or —OCH 3 ;
or a pharmaceutically acceptable salt thereof.
25. The compound of claim 1 , where R5 is H.
26. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
27. The compound of claim 1 , wherein the halogen is Br, Cl or F.
28. The compound of claim 1 having the structure:
or a pharmaceutically acceptable salt thereof.
29. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.
30. A method of treating rheumatoid arthritis in a subject comprising administering a compound of claim 1 to the subject in an amount effective to treat rheumatoid arthritis.
31. A compound having the structure:
or a pharmaceutically acceptable salt thereof.