MK2 inhibitors and uses thereof
The present invention provides compounds, compositions thereof, and methods of using the same.
1. A compound of formula III:
or a pharmaceutically acceptable salt thereof, wherein:
T is —NH— or —O—;
each R is independently hydrogen or an optionally substituted C 1-6 aliphatic, or:
two R groups on the same nitrogen are taken together with the nitrogen to form a 3-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms selected from nitrogen, oxygen, or sulfur;
R 1 is methyl;
R 2 is halogen, —CN, —SR y , —S(O)R y , —SO 2 R y , —OSO 2 R y , —OC(O)R y , or —OP(O) 2 OR y ;
each R y is independently selected from optionally substituted C 1-6 aliphatic or optionally substituted phenyl;
R 3 is hydrogen, optionally substituted C 1-6 aliphatic, —CN, —NO 2 , halogen, —OR, —N(R) 2 , —C(O)N(R) 2 , —C(O)OR, -Cy, —C(O)N(R)-Cy, —C(O)-Cy, —O-Cy, —O—(CH 2 ) n -Cy, —(CH 2 ) n —O-Cy, —N(R)-Cy, —N(R)—(CH 2 ) n -Cy, —(CH 2 ) n —N(R)-Cy, or —(CH 2 ) m -Cy;
each of m and n is independently 0-4; and
each Cy is independently an optionally substituted ring selected from a 3-9 membered saturated or partially unsaturated monocyclic carbocyclic ring, a 3-9 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, phenyl, a 5-6 membered heteroaryl ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 7-12 membered saturated or partially unsaturated fused or bridged bicyclic carbocyclic ring, or a 7-12 membered saturated or partially unsaturated fused or bridged bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.
2. The compound according to claim 1 , wherein -T- is —O—.
3. The compound according to claim 1 , wherein R 2 is halogen.
4. The compound according to claim 3 wherein R 2 is chloro.
5. The compound according to claim 1 , wherein R 3 is selected from —N(R) 2 , -Cy, —C(O)N(R)-Cy, —C(O)-Cy, —O-Cy, —O—(CH 2 ) n -Cy, —(CH 2 ) n —O-Cy, —N(R)-Cy, —N(R)—(CH 2 ) n -Cy, —(CH 2 ) n —N(R)-Cy, or —(CH 2 ) m -Cy.
6. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from a 3-7 membered saturated or partially unsaturated carbocyclic ring.
7. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.
8. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from oxetanyl, piperidinyl, pyrrolidinyl tetrahydrofuranyl, piperazinyl, and morpholinyl.
9. The compound according to claim 5 , wherein each -Cy is independently an optionally substituted ring selected from a 7-12 membered saturated or partially unsaturated fused or bridged bicyclic heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur.
10. The compound according to claim 5 , wherein -Cy is substituted with a group selected from halogen, —(CH 2 ) 0-4 R ∘ , —(CH 2 ) 0-4 OR ∘ , or —(CH 2 ) 0-4 N(R ∘ ) 2 , wherein each R ∘ is independently hydrogen or C 1-6 aliphatic optionally substituted with halogen or —OR ● , wherein R ● is C 1-4 aliphatic.
11. The compound according to claim 1 , wherein R 3 is optionally substituted C 1-6 aliphatic.
12. The compound according to claim 11 , wherein R 3 is C 1-6 aliphatic optionally substituted with a group selected from —(CH 2 ) 0-4 OR ∘ , —(CH 2 ) 0-4 N(R ∘ ) 2 , or —(CH 2 ) 0-4 SO 2 R ∘ , wherein each R ∘ is independently hydrogen, a 5-6 membered saturated, partially unsaturated or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or C 1-6 aliphatic optionally substituted with halogen, —CN, —(CH 2 ) 0-2 R ● , or —(CH 2 ) 0-2 OR ● , wherein R ● is C 1-4 aliphatic.
13. The compound according to claim 12 , wherein R 3 is C 1-6 aliphatic substituted with —(CH 2 ) 0-4 OR ∘ , wherein R ∘ is hydrogen or C 1-6 aliphatic optionally substituted with halogen, —CN, or —(CH 2 ) 0-2 OR ● , wherein R ● is C 1-4 aliphatic.
14. The compound according to claim 12 , wherein R 3 is C 1-6 aliphatic substituted with —(CH 2 ) 0-4 N(R ∘ ) 2 , wherein each R ∘ is independently hydrogen or C 1-6 aliphatic optionally substituted with —(CH 2 ) 0-2 OR ● , wherein R ● is C 1-4 aliphatic.
15. The compound according to claim 13 , wherein R 3 is C 1-6 aliphatic substituted with —(CH 2 ) 0-4 OR ∘ , wherein R ∘ is hydrogen or C 1-6 aliphatic optionally substituted with halogen.
16. The compound according to claim 1 selected from:
or a pharmaceutically acceptable salt thereof.
17. The compound according to claim 1 selected from:
or a pharmaceutically acceptable salt thereof.
18. A pharmaceutically acceptable composition comprising the compound according to claim 1 and a pharmaceutically acceptable carrier, adjuvant, or vehicle.