THERAPEUTICALLY ACTIVE COMPOSITIONS AND THEIR METHODS OF USE

• US 20130035329A1
• Filed: 06/08/2012
• Published: 02/07/2013
• Est. Priority Date: 12/09/2009
• Status: Abandoned Application

• Current Assignee: Servier Pharmaceuticals LLC (Servier Sas)
• Original Assignee: Servier Pharmaceuticals LLC (Servier Sas)
• Inventors: Saunders, Jeffrey O., Salituro, Francesco G.
• Application Number:
  US13/492,159
• Publication Number:
  US 20130035329A1
• Time in Patent Office: Days
• US Class Current: 514/218
• CPC Class Codes: A61K 31/495 having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazinesA61K31/48 takes precedence ; with three nitrogen atoms A61K31/53
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
• CPC Class Codes: A61K 31/551 having two nitrogen atoms, e.g. dilazep
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 209/04 Indoles; Hydrogenated indoles
• CPC Class Codes: C07D 213/71 to which a second hetero atom is attached
• CPC Class Codes: C07D 213/72 Nitrogen atoms nitro radicals C07D213/61
• CPC Class Codes: C07D 215/38 Nitrogen atoms nitro radicals C07D215/18
• CPC Class Codes: C07D 239/42 One nitrogen atom nitro radicals C07D239/30
• CPC Class Codes: C07D 243/08 not condensed with other rings
• CPC Class Codes: C07D 249/04 1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
• CPC Class Codes: C07D 271/10 1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
• CPC Class Codes: C07D 295/192 from aromatic carboxylic acids
• CPC Class Codes: C07D 471/04 Ortho-condensed systems

Abstract

Compounds and compositions comprising compounds useful in the treatment of cancer are described herein.

Claims

1. A method of treating a cancer characterized as having an IDH mutation, the method comprising administering to a subject a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein:

2. The method of claim 1, wherein the compound is selected from any one of the compounds set forth in the table below:

3. The method of claim 1 or 2, wherein the compound or pharmaceutically acceptable salt thereof is formulated into a pharmaceutical together with a pharmaceutically acceptable carrier.

4. The method of any one of claims 1 to 3, wherein the subject is evaluated for the presence of an IDH1 R132X mutant allele prior to administration of the compound.

5. The method of any one of claims 1 to 3, wherein the subject is evaluated for the presence of an elevated level of 2HG prior to administration of the compound.

6. The method of any one of claims 1 to 3, wherein efficacy of treatment of cancer comprises monitoring the level of 2HG in a subject during treatment.

7. The method of any one of claims 1 to 3, wherein efficacy of treatment of cancer comprises monitoring the level of 2HG in a subject following termination of treatment.

8. (canceled)

9. A compound of formula (Ic):

10. The compound of claim 9, wherein the compound is a compound of formula (II):

11. The compound of claim 9, wherein the compound is a compound of formula (III):

12. The compound of claim 11, wherein B and B¹ are taken together with the carbon atoms to which they are attached to form a carbonyl group.

13. The compound of claim 11, wherein D is a bond and D¹ is NR^c.

14. The compound of claim 9, wherein the compound is a compound of formula (IV):

15. The compound of claim 14, wherein D is a bond and D¹ is NR^c.

16. The compound of claim 15, wherein R^c is hydrogen.

17. The compound of claim 14, wherein R¹ is aralkyl or heteroaralkyl substituted with 0-3 occurrences of R^d.

18. The compound of claim 14, wherein A is phenyl substituted with 0-3 occurrences of R².