3-phosphoglycerate dehydrogenase inhibitors and uses thereof

1. A compound of formula I:

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is methyl;

R 2 is F, Cl, —CF 3 , —OCF 3 , —OCHF 2 , —OCH 2 Ph, —OCH 3 , —CN, —CH 3 ,

R 3 is halogen, —OR, —CN, or C 1-6 aliphatic optionally substituted with 1, 2, or 3 halogens; or R 2 and R 3 are optionally taken together with the carbon atoms to which they are attached and any intervening atoms to form a 5-8 membered partially unsaturated ring having 0-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R 4 is hydrogen, halogen, —OR 5 , —CN, or C 1-6 aliphatic optionally substituted with 1, 2, or 3 halogens;

each R is independently hydrogen or an optionally substituted group selected from C 1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, or sulfur;

R 5 is hydrogen, —(CH 2 ) n -phenyl, or C 1-6 alkyl optionally substituted with 1, 2, or 3 halogens;

R 6 is hydrogen or C 1-4 alkyl;

R 7 is hydrogen or —CO 2 R;

L 1 is a C 1-8 bivalent straight or branched hydrocarbon chain wherein 1-5 methylene units of the chain are independently and optionally replaced with —O—, —C(O)—, —C(O)O—, —OC(O)—, —N(R)—, —C(O)N(R)—, —(R)NC(O)—, —OC(O)N(R)—, —(R)NC(O)O—, —N(R)C(O)N(R)—, —S—, —SO—, —SO 2 —, —SO 2 N(R)—, —(R)NSO 2 —, —C(S)—, —C(S)O—, —OC(S)—, —C(S)N(R)—, —(R)NC(S)—, —(R)NC(S)N(R)—, or -Cy-;

each -Cy- is independently a bivalent 6-membered arylene ring containing 0-2 nitrogen atoms, or a bivalent 5-membered heteroarylene ring with 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or a bivalent partially unsaturated 8-10 membered bicyclic heterocyclene ring with 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein -Cy- is optionally substituted with 1 or 2 substituents independently selected from C 1-4 alkyl or —OR; and

n is independently 0, 1, 2, 3, 4, or 5.

2. The compound according to claim 1 , wherein R 2 is F, Cl, —OCF3, —OCF2, —OCH2Ph, —OCH3 or —CN.

3. The compound according to claim 1 , wherein R 3 is halogen or —OR.

4. The compound according to claim 1 , wherein R2 is F or Cl and R3 is halogen.

5. The compound according to claim 4 , wherein R 4 is hydrogen.

6. The compound according to claim 1 , wherein R 5 is hydrogen, —(CH 2 ) n -phenyl, or C 1-6 alkyl optionally substituted with 1, 2, or 3 halogens.

7. The compound according to claim 1 , wherein L 1 is

8. The compound according to claim 7 , wherein L 1 is

9. The compound according to claim 1 , wherein said compound is of Formulae II-a, II-b, II-c, II-d, II-e, II-f, or II-g:

or a pharmaceutically acceptable salt thereof.

10. A compound selected from:

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle.

12. A pharmaceutical composition comprising a compound according to claim 10 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable adjuvant, carrier, or vehicle.