ERK inhibitors and uses thereof
Compounds, compositions thereof, and methods for inhibiting one or both ERK1 and ERK2 kinases are provided.
1. A compound of formula II-a:
or a pharmaceutically acceptable salt thereof, wherein:
R 1 is selected from:
each R 2 is independently hydrogen, an optionally substituted C 1-6 aliphatic, halogen, or —OR;
Ring B is an optionally substituted group selected from a 3-7 membered saturated or partially unsaturated carbocyclic ring, a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 7-12 membered bicyclic saturated, partially unsaturated or aryl ring, a 7-12 membered bicyclic saturated or partially unsaturated heterocyclic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-12 membered bicyclic heteroaryl ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;
each R 3 is independently selected from —R, —Cy, halogen, —OR, —SR, —CN, —NO 2 , —SO 2 NR, —SO 2 R, —SOR, —C(O)R, —C(O)OR, —OC(O)R, —OC(O)N(R) 2 , —C(O)N(R) 2 , —C(O)N(R)—OR—C(O)C(O)R, —P(O)(R) 2 , —NRC(O)OR, —NRC(O)R, —NRC(O)N(R) 2 , —NRSO 2 R, or —N(R) 2 ;
or two R 3 groups on the same carbon atom together form —C(O)—, —C(S)—, or —C(N—R)—;
each R is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, phenyl, a 3-8 membered saturated or partially unsaturated carbocyclic ring, a 4-7 membered heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or
two R groups on the same nitrogen are taken together with the nitrogen atom to which they are attached to form a 4-7 membered heterocyclic ring having 0-2 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a 4-7 membered heteroaryl ring having 0-4 additional heteroatoms independently selected from nitrogen, oxygen, or sulfur;
Cy is an optionally substituted 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an optionally substituted 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; and
m and p are each independently 0-4.
2. The compound according claim 1 , wherein p is 0.
3. The compound according to claim 1 , wherein p is 1.
4. The compound according to claim 1 , wherein p is 2.
5. The compound according claim 1 , wherein m is 0.
6. The compound according to claim 1 , wherein m is 1.
7. The compound according to claim 1 , wherein m is 2.
8. The compound according to claim 1 , wherein R 1 is:
9. The compound according claim 1 , wherein at least one R 2 is optionally substituted C 1-6 aliphatic.
10. The compound according to claim 9 , wherein at least one R 2 is methyl.
11. The compound according to claim 1 , wherein at least one R 2 is halogen.
12. The compound according to claim 11 , wherein at least one R 2 is fluoro.
13. The compound according to claim 1 , wherein at least one R 3 is independently selected from —R, halogen, —OR, —SO 2 R, —C(O)R, —C(O)OR, —C(O)N(R) 2 , —C(O)N(R)—OR or —C(O)C(O)R.
14. The compound according to claim 1 , wherein two R 3 groups on the same carbon atom together form —C(O)—.
15. The compound according to claim 13 , wherein at least one R 3 is —R.
16. The compound according to claim 13 , wherein at least one R 3 is —OR.
17. A compound selected from the group consisting of:
or a pharmaceutically acceptable salt thereof.