Claims for Patent: RE49582

Summary for Patent: RE49582

Title:	Therapeutic compounds and compositions
Abstract:	Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
Inventor(s):	Francesco G. Salituro, Jeffrey O. Saunders, Shunqi Yan
Assignee:	Schroedinger LLC, Agios Pharmaceuticals Inc
Application Number:	US17/131,562
Patent Claims:	1. A compound of formula II or a pharmaceutically acceptable salt thereof, wherein: W, X, Y and Z are each independently selected from CH or N; D and D1 are independently selected from a bond or NRb; L is a bond, —C(O)—, —(CRcRc)m—, —OC(O)—, —(CRcRc)m—OC(O)—, —(CRcRc)m—C(O)—, —NRbC(S)—, or —NRbC(O)— (wherein the point of the attachment to R1 is on the left-hand side); R1 is selected from alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; each of which is substituted with 0-5 occurrences of Rd; each R3 is independently selected from halo, haloalkyl, alkyl, hydroxyl and —ORa or two adjacent R3 taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl; each Ra is independently selected from alkyl, acyl, hydroxyalkyl and haloalkyl; each Rb is independently selected from hydrogen and alkyl; each Rc is independently selected from hydrogen, halo, alkyl, alkoxy and halo alkoxy or two Rc taken together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl; each Rd is independently selected from halo, haloalkyl, haloalkoxy, alkyl, alkynyl, nitro, cyano, hydroxyl, —C(O)Ra, —OC(O)Ra, —C(O)ORa, —SRa, —NRaRb and —ORa, or two Rd taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl; n is 0, 1, or 2; m is 1, 2 or 3; h is 1; and g is 1. 2. The compound of claim 1, wherein W, X, Y and Z are CH. 3. The compound of claim 2, wherein D is NRb and D1 is a bond. 4. The compound of claim 3, wherein Rb is H, methyl or ethyl. 5. The compound of claim 1, wherein L is a bond, —(CRcRc)m—, —NRbC(O)—, —(CRcRc)m—C(O)—, —C(O)—, or —O(CO)— —OC(O)—. 6. The compound of claim 5, wherein L is a bond. 7. The compound of claim 6, wherein R1 is alkyl, aryl or heteroaryl, each substituted with 0-5 occurrences of Rd. 8. The compound of claim 5, wherein L is —(CRcRc)m—. 9. The compound of claim 8, wherein R1 is cycloalkyl, aryl, heteroaryl or heterocyclyl, each substituted with 0-5 occurrences of Rd. 10. The compound of claim 5, wherein L is —NRbC(O)— and Rb is hydrogen. 11. The compound of claim 10, wherein R1 is aryl substituted with 0-5 occurrences of Rd. 12. The compound of claim 5, wherein L is —(CRcRc)m—C(O)—. 13. The compound of claim 12, wherein R1 is cycloalkyl, aryl or heteroaryl, each substituted with 0-5 occurrences of Rd. 14. The compound of claim 5, wherein L is —C(O)—. 15. The compound of claim 14, wherein R1 is aryl, alkyl, or heteroaryl, each substituted with 0-5 occurrences of Rd. 16. The compound of claim 5, wherein L is —OC(O)—. 17. The compound of claim 16, wherein R1 is alkyl, aryl or heterocyclyl, each substituted with 0-5 occurrences of Rd. 18. The compound of claim 1, wherein L is —(CRcRc)m—OC(O)—. 19. The compound of claim 18, wherein R1 is heterocyclyl or cycloalkyl, each substituted with 0-5 occurrences of Rd. 20. The compound of claim 5, wherein n is 0. 21. The compound of claim 5, wherein n is 1 and R3 is CH3, CH2CH3, OCH3, OCH2CH3, OH, F, Cl, or CF3. 22. A pharmaceutical composition comprising a compound of formula II or a pharmaceutically acceptable salt thereof, wherein: W, X, Y and Z are each independently selected from CH or N; D and D1 are independently selected from a bond or NRb; L is a bond, —C(O)—, —(CRcRc)m—, —OC(O)—, —(CRcRc)m—OC(O)—, —(CRcRc)m—C(O)—, —NRbC(S)—, or —NRbC(O)— (wherein the point of the attachment to R1 is on the left-hand side); R1 is selected from alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl; each of which is substituted with 0-5 occurrences of Rd; each R3 is independently selected from halo, haloalkyl, alkyl, hydroxyl and —ORa, or two adjacent R3 taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl; each Ra is independently selected from alkyl, acyl, hydroxyalkyl and haloalkyl; each Rb is independently selected from hydrogen and alkyl; each Rc is independently selected from hydrogen, halo, alkyl, alkoxy and halo alkoxy or two Rc taken together with the carbon atoms to which they are attached form an optionally substituted cycloalkyl; each Rd is independently selected from halo, haloalkyl, haloalkoxy, alkyl, alkynyl, nitro, cyano, hydroxyl, —C(O)Ra, —OC(O)Ra, —C(O)ORa, —SRa, —NRaRb and —ORa, or two Rd taken together with the carbon atoms to which they are attached form an optionally substituted heterocyclyl; n is 0, 1, or 2; m is 1, 2 or 3; h is 1; and g is 1. 23. The pharmaceutical composition of claim 22, wherein the compound is a compound of formula: 24. The compound of claim 1, wherein the compound is selected from the following: 25. The compound of claim 1 selected from the following: 26. The compoud of claim 1 selected from: 27. The compound of claim 1 selected from: 28. The compound of claim 1 selected from: 29. The compound of claim 1 selected from: 30. The compound of claim 1 selected from: 31. The compound of claim 1 selected from: 32. The compound of claim 1 selected from: 33. The compound of claim 1 selected from: 34. The compound of claim 1 selected from: 35. The compound of claim 1 selected from: 36. The compound of claim 1 selected from: 37. The compound of claim 1 selected from: 38. The compound of claim 1 selected from: 39. The compound of claim 1 selected from: 40. The compound of claim 1 selected from: 41. The compound of claim 1 selected from: 42. The compound of claim 1 selected from: 43. The compound of claim 1 selected from: 44. The compound of claim 1 selected from: 45. The compound of claim 1 selected from: 46. The compound of claim 1 selected from: 47. The compound of claim 1 selected from: 48. The compound of claim 1 selected from: 49. A compound selected from one of the following: 50. A pharmaceutical composition comprising a compound of any one of claims 2 to 21, or a pharmaceutically acceptable salt thereof, or a compound of claim 49. 51. A pharmaceutical composition comprising a compound of claim 24 selected from the following: or a pharmaceutically acceptable salt thereof. 52. A pharmaceutically acceptable salt of the compound: 53. A compound or a pharmaceutically acceptable salt thereof, wherein the compound is: 54. A pharmaceutical composition comprising a pharmaceutically acceptable salt of the compound: 55. A pharmaceutical composition comprising a compound or a pharmaceutically acceptable salt thereof, wherein the compound is: 56. The pharmaceutical composition of claim 54 further comprising a pharmaceutically acceptable carrier. 57. The pharmaceutical composition of claim 55 further comprising a pharmaceutically acceptable carrier.