Heteroaryl compounds and uses thereof
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. A method for inhibiting the activity of BTK, or a mutant thereof, in a biological sample comprising the step of contacting said biological sample with a compound of Formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
X and X′ are each independently O;
p and q are each independently 0 or 1, wherein p and q are not both 1;
R 1 is OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;
R′ is —H, —CH 3 , —SO 3 H or -Glu;
each Glu is a glucuronyl moiety;
R 4 is —H, —OH, —OSO 3 H or —OGlu;
R x and R y are each independently —OH, —OSO 3 H, or —OGlu;
R z , R z′ and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu; and
m and n are each independently 0, 1, 2, 3 or 4,
provided that at least one of the following is true:
(a) R 1 is —OH, —OSO 3 H, —OGlu, —OCH 2 CH 2 OH, —OCH 2 CO 2 H, —OCH 2 CH 2 OSO 3 H or —OCH 2 CH 2 OGlu;
(b) at least one of R 4 , R z , R z′ and R z″ is —OH, —OSO 3 H or —OGlu;
(c) at least one of m and n is 1, 2, 3 or 4; or
(d) one of p or q is 1.
2. The method according to claim 1 , wherein R 1 is —OCH 2 CH 2 OR′.
3. The method according to claim 2 , wherein R′ is —H.
4. The method according to claim 2 , wherein R′ is —CH 3 .
5. The method according to claim 1 , wherein R 1 is —OH.
6. The method according to claim 1 , wherein R 1 is —OCH 2 CO 2 H.
7. The method according to claim 1 , wherein R 4 is —OH.
8. The method according to claim 1 , wherein m is 1 and R x is —OH.
9. The method according to claim 8 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
10. The method according to claim 1 , wherein n is 1 and R y is —OH.
11. The method according to claim 10 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
12. The method according to claim 1 , wherein:
R 1 is —OH, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H;
R′ is —H or —CH 3 ;
R 4 is —H or —OH;
R x and R y are each independently —OH; and
m and n are each independently 0, 1, 2, 3 or 4;
provided that at least one of the following is true:
(a) R 1 is —OH, —OCH 2 CH 2 OH or —OCH 2 CO 2 H; or
(b) R 4 is —OH; or
(c) at least one of m and n is 1, 2, 3 or 4.
13. The method according to claim 12 , wherein R 1 is —OCH 2 CH 2 OR′.
14. The method according to claim 13 , wherein R′ is —H.
15. The method according to claim 13 , wherein R′ is —CH 3 .
16. The method according to claim 12 , wherein R 1 is —OH.
17. The method according to claim 12 , wherein R 1 is —OCH 2 CO 2 H.
18. The method according to claim 12 , wherein R 4 is —OH.
19. The method according to claim 12 , wherein m is 1 and R x is —OH.
20. The method according to claim 19 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
21. The method according to claim 12 , wherein n is 1 and R y is —OH.
22. The method according to claim 21 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
23. The method according to claim 1 , wherein the compound is selected from the group consisting of
24. The method of claim 1 , wherein the biological sample comprises one or more cells obtained from a patient.
25. The method of claim 1 , wherein the biological sample is a cell line.