Heteroaryl compounds useful as MK2 inhibitors
The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
1. A compound of Formulae IV, IV′, or IV″:
or a pharmaceutically acceptable salt thereof, wherein:
R 2 is hydrogen, —OH, —OSO 3 H, —OGlu, or —SR 11 ;
R 3 is —C(R′) 2 OC(R″) 2 C(R′″) 3 , —C(R′) 2 OR w ;
each of R′ and R″ is independently hydrogen or deuterium;
R w is hydrogen, —SO 3 H or -Glu;
each Glu is a glucuronyl moiety;
R xa , R xb , R ya , and R yb are each independently hydrogen, deuterium;
R 4 is hydrogen or deuterium;
R 7 and R 7′ are each independently hydrogen, deuterium, —OH, —OSO 3 H, or —OGlu; or
R 7 and R 7′ are taken together to form ═O;
R 8 is hydrogen, deuterium, —OH, —OSO 3 H or —OGlu;
R 8′ and R 8″ are each independently hydrogen or deuterium; or
R 8′ and R 8″ are taken together to form ═O;
R 9 is hydrogen, deuterium, —OH, —OSO 3 H or —OGlu; and
R 11 is selected from:
2. The compound according to claim 1 , wherein
R 2 is hydrogen, —OH, or —SR″;
R 3 is —C(R′) 2 OC(R″) 2 C(R′″) 3 or —C(R′) 2 OR w ;
each R′, R″, and R′″ is independently hydrogen or deuterium;
R w is hydrogen;
R 9 is hydrogen, deuterium, or —OH;
R 7 and R 7′ are each independently hydrogen, deuterium, or —OH; or
R 7 and R 7′ are taken together to form ═O;
R 8 is hydrogen, deuterium, or —OH; and
R 8′ and R 8 ″ are each independently hydrogen or deuterium; or
R 8′ and R 8″ are taken together to form ═O.
3. The compound according to claim 1 , wherein at least one of the following is true:
(a) at least one of R 7 , R 7′ , R 8 , or R 9 is —OH, —OSO 3 H or —OGlu;
(b) R 7 and R 7′ are taken together to form ═O; or
(c) R 8′ and R 8″ are taken together to form ═O.
4. The compound according to claim 1 , wherein at least one of the following is true:
(a) at least one of R 7 , R 7′ , R 8 , or R 9 is —OH;
(b) R 7 and R 7′ are taken together to form ═O; or
(c) R 8′ and R 8″ are taken together to form ═O.
5. The compound according to claim 1 , wherein the compound is selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.
6. A pharmaceutical composition comprising a compound according to claim 1 , and a pharmaceutically acceptable adjuvant, carrier, or vehicle.
7. A pharmaceutical composition comprising a compound according to claim 5 , and a pharmaceutically acceptable adjuvant, carrier, or vehicle.
8. The compound according to claim 1 , wherein each of R xa , R xb , R ya , and R yb is hydrogen.
9. The compound according to claim 1 , wherein each of R 7 , R 7′ , R 8′ , R 8′ , R 8″ , and R 9 is hydrogen.
10. The compound according to claim 1 , wherein each of R 7 , R 7′ , R 8′ , R 8′ , R 8″ , and R 9 is deuterium.
11. The compound according to claim 1 , wherein R 3 is —C(R′) 2 OC(R″) 2 C(R″) 3 .
12. The compound according to claim 1 , wherein R 3 is —C(R 1 ) 2 OR w .
13. The compound according to claim 12 , wherein R w is hydrogen.
14. The compound according to claim 1 , wherein R 2 is —SR 11 .
15. The compound according to claim 14 , wherein R 11 is
16. The compound according to claim 15 , wherein R 11 is:
17. The compound according to claim 15 , wherein R 11 is: