Processing

Please wait...

Settings

Settings

Goto Application

1. WO2020198067 - PKM2 MODULATORS AND METHODS FOR THEIR USE

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

[ EN ]

CLAIMS

1. A compound having the following structure (I):


or a pharmaceutically acceptable salt, isotopic form, tautomer or prodrug thereof, wherein:

R1 is F or NFL,

R2 is H, Cl or Br; or R2 joins with R3 to form an optionally substituted heteroaryl; and

R3 is H or optionally substituted C1-C6 alkyl; or R3 joins with R2 to form an optionally substituted heteroaryl.

2. The compound of claim 1, wherein:

R1 is F or NFL,

R2 is H, Cl or Br; and

R3 is H or optionally substituted C1-C6 alkyl.

3. The compound of claim 1 or 2, wherein R3 is H.

4. The compound of claim 1 or 2, wherein R3 is methyl or aminom ethyl.

5. The compound of any one of claims 1-4, wherein R2 is H.

6. The compound of claim 1, wherein:

R1 is F or NH2,

R2 is Cl or Br; and

R3 is H.

7. The compound of claim 6, wherein R1 is F.

8. The compound of claim 6, wherein R1 is NH2.

9. The compound of claim 6, wherein R2 is Cl.

10. The compound of claim 6, wherein R2 is Br.

11. The compound of claim 1, wherein R2 and R3 join to form a 5-membered optionally substituted heteroaryl.

12. The compound of claim 11, wherein R1 is F.

13. The compound of claim 11, wherein R1 is NH2.

14. A compound having one of the following structures (la), (lb), (Ic), (Id), (Ie), (If), (Ig), (Ih), (Ii), or (Ij):


(Ii) (Ij)

or a pharmaceutically acceptable salt, isotopic form, tautomer or prodrug thereof.

15. A pharmaceutical composition comprising the compound of any one of claims 1-14, or a pharmaceutically acceptable salt, isotopic form, tautomer or prodrug thereof, and a pharmaceutically acceptable carrier or excipient.

16. A method for modulating pyruvate kinase muscle isozyme M2 (PKM2) activity in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound of any one of claims 1-14, or a tautomer, pharmaceutically acceptable salt or prodrug thereof, or the composition of claim 15 to the subject.

17. A method for treating cancer in a subject in need thereof, the method comprising administering a therapeutically effective amount of the compound of any one of claims 1-14, or a tautomer, pharmaceutically acceptable salt or prodrug thereof, or the composition of claim 15 to the subject.

18. The method of claim 17, wherein the cancer is an advanced solid tumor resistant to treatment with an immuno-oncology (10) agent and the cancer is NPM-ALK anaplastic large cell lymphoma.

19. The method of claim 17, wherein the cancer is an EGFR-mutant non-small cell lung cancer resistant to treatment with a tyrosine kinase inhibitor.

20. The method of any one of claims 16-19, further comprising administering, or instructing the administration of, a diet low in serine and/or glycine to the subject.