Heteroaryl compounds and uses thereof
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. 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 —OCH 2 CO 2 H, —OH, —OCH 3 , —OSO 3 H, —OGlu, —OCH 2 CH 2 OCH 3 , —OCH 2 CH 2 OSO 3 H, or —OCH 2 CH 2 OGlu;
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 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 compound according to claim 1 , wherein:
R 4 is —H or —OH;
R x and R y are each independently —OH; and
R z , R z′ and R z″ are each independently —H, —CH 3 or —OH;
provided that at least one of the following is true:
(a) R 1 is —OH or —OCH 2 CO 2 H;
(b) at least one of R 4 , R z , R z′ and R z′ is —OH;
(c) at least one of m and n is 1, 2, 3 or 4; or
(d) one of p or q is 1.
3. The compound according to claim 1 , wherein R 1 is——OCH 2 CH 2 OCH 3 .
4. The compound according to claim 1 , wherein the compound has the structure of Formula IV:
or a pharmaceutically acceptable salt thereof.
5. The compound according to claim 4 , wherein R 1 is— —OCH 2 CH 2 OCH 3 .
6. The compound according to claim 4 , wherein R 1 is —OH.
7. The compound according to claim 4 , wherein R 1 is —OCH 2 CO 2 H.
8. The compound according to claim 4 , wherein R 4 is —OH.
9. The compound according to claim 4 , wherein m is 1 and R x is —OH.
10. The compound according to claim 4 , wherein:
R 4 is —H or —OH; and
R x and R y are each independently —OH;
provided that at least one of the following is true:
(a) R 1 is —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.
11. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof wherein:
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 y is —OH, —OSO 3 H, or —OGlu; and
n is 0, 1, 2, 3 or 4.
12. A composition comprising a compound according to claim 1 , and a pharmaceutically acceptable adjuvant, carrier, or vehicle.
13. A compound of Formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
X and X′ are each independently O;
p is 1 and q is 0;
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.
14. A compound of Formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
X and X′ are each independently O;
p is 0 and q is 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.
15. A compound of Formula I-a
or a pharmaceutically acceptable salt thereof, wherein:
R z is selected from —CH 3 , —OH, —OSO 3 H, and —OGlu;
R z′ and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu;
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; and
m and n are each independently 0, 1, 2, 3 or 4.
16. The compound according to claim 15 , wherein R z is —OH.
17. The compound according to claim 15 , wherein R z is —CH 3 .
18. A compound of Formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
R z′ is selected from —CH 3 , —OH, —OSO 3 H, and —OGlu;
R z and R z″ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu;
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; and
m and n are each independently 0, 1, 2, 3 or 4.
19. The compound according to claim 18 , wherein R z′ is —OH.
20. The compound according to claim 18 , wherein R z′ is —CH 3 .
21. A compound of Formula I-a:
or a pharmaceutically acceptable salt thereof, wherein:
R z″ is selected from —CH 3 , —OH, —OSO 3 H, and —OGlu;
R z and R z′ are each independently —H, —CH 3 , —OH, —OSO 3 H, or —OGlu;
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; and
m and n are each independently 0, 1, 2, 3 or 4.
22. The compound according to claim 21 , wherein R z″ is —OH.
23. The compound according to claim 21 , wherein R z′ is —CH 3 .
24. A compound of Formula IV
or a pharmaceutically acceptable salt thereof wherein:
R 1 is —OR′, —OCH 2 CH 2 OR′ or —OCH 2 CO 2 H; or R 1 is —OCH 2 CH 2 OR′ wherein R′ is —CH 3 , —SO 3 H or -Glu;
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 is —OH, —OSO 3 H, or —OGlu;
R y is —OH;
m is 0, 1, 2, 3 or 4; and
n is 1.