eIF4E inhibitors and uses thereof

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

Ring A is an optionally substituted ring selected from phenyl, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3-7 membered monocyclic, saturated or partially unsaturated, carbocyclic ring, a 3-7 membered monocyclic, saturated or partially unsaturated, heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic aromatic carbocyclic ring, and an 8-10 membered bicyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur;

L 1 is a bond or an optionally substituted C 1-8 bivalent straight or branched hydrocarbon chain, wherein 1, 2, 3, or 4 methylene units of the hydrocarbon chain are optionally and independently replaced with —O—, —S—, —N(R)—, —C(O)—, or —S(O) 2 —;

R 2 is —C 1-6 alkyl, —C 1-6 alkyl substituted 1-6 times by halogen, or an optionally substituted 3-7 membered monocyclic, saturated or partially unsaturated, carbocyclic ring;

L 2 is

R 3 is —CN, —C(O)R, —C(O)OR, —C(O)N(R) 2 , —N(R)—C(O)—R, —N(R)—C(O)—OR, —S(O) 2 —N(R) 2 , —S(O) 2 —N(R)—C(O)R, —C(O)—N(R)—S(O) 2 R, —C(═NR)—N(R) 2 , —N(R)—C(═NR)—N(R) 2 , or a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and

R is hydrogen, optionally substituted —C 1-6 aliphatic, or an optionally substituted ring selected from phenyl, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 3-7 membered monocyclic, saturated or partially unsaturated, carbocyclic ring, and a 3-7 membered monocyclic, saturated or partially unsaturated, heterocyclic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

2. The compound of claim 1 , wherein Ring A is optionally substituted phenyl.

3. The compound of claim 2 , wherein Ring A is

wherein each of R 11 and R 12 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R.

4. The compound of claim 1 , wherein L 1 is a bond.

5. The compound of claim 1 , wherein R 2 is —C 1-6 alkyl.

6. The compound of claim 1 , wherein R 2 is

7. The compound of claim 1 , wherein R 3 is —COOH.

8. The compound of claim 1 , wherein the compound is of Formula III:

or a pharmaceutically acceptable salt thereof, wherein R 1 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R, and n is 0, 1, 2, 3, 4, or 5.

9. The compound of claim 1 , wherein the compound is of any one of Formulae III-a to III-d:

or a pharmaceutically acceptable salt thereof, wherein each of R 11 and R 12 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R.

10. The compound of claim 1 , wherein the compound is of any one of Formulae V-a to V-d:

or a pharmaceutically acceptable salt thereof, wherein each of R 11 and R 12 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R.

11. The compound of claim 1 , wherein the compound is of any one of Formulae VII-a to VII-d:

or a pharmaceutically acceptable salt thereof, wherein each of R 11 and R 12 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from:

13. A pharmaceutical composition comprising the compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

14. The compound of claim 1 , wherein the compound is of Formula V:

or a pharmaceutically acceptable salt thereof, wherein R 1 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R, and n is 0, 1, 2, 3, 4, or 5.

15. The compound of claim 1 , wherein the compound is of Formula VII:

or a pharmaceutically acceptable salt thereof, wherein R 1 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R, and n is 0, 1, 2, 3, 4, or 5.

16. The compound of claim 1 , wherein the compound is of any one of Formulae IV, IV-a, IV-b, IV-c, or IV-d:

or a pharmaceutically acceptable salt thereof, wherein R 1 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R; each of R 11 and R 12 is independently halogen, R, —N(R) 2 , —OR, —SR, —C(O)OR, or —S(O) 2 R; and n is 0, 1, 2, 3, 4, or 5.