INHIBITORS OF HISTONE DEMETHYLASES

• US 20140371195A1
• Filed: 08/28/2014
• Published: 12/18/2014
• Est. Priority Date: 10/02/2012
• Status: Active Grant

• Current Assignee: Gilead Sciences Inc.
• Original Assignee: EpiTherapeutics ApS (Gilead Sciences Inc.)
• Inventors: Mehrotra, Mukund, Labelle, Marc, Boesen, Thomas, Khan, Qasim, Ullah, Farman
• Granted Patent: US 10,189,787 B2
• Time in Patent Office: Days
• US Class Current: 514/210.2
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/443 containing a five-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/79 Acids; Esters
• CPC Class Codes: C07D 401/06 linked by a carbon chain containing only aliphatic carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links

Abstract

The present application discloses compounds capable of modulating the activity of histone demethylases (HDMEs), which are useful for prevention and/or treatment of diseases in which genomic dysregulation is involved in the pathogenesis, such as e.g. cancer. The present application also discloses pharmaceutical compositions comprising said compounds and the use of such compounds as a medicament. The compounds take the form

Claims

1. A compound of Formula (I)

2. The compound of claim 1, having the structure

3. The compound of claim 1, wherein the compound is an acid addition salt.

4. The compound of claim 3, wherein the acid is selected from succinic, maleic, acetic, fumaric, citric, tartaric, benzoic, trifluoroacetic, malic, lactic, formic, propionic, glycolic, gluconic, camphorsulfuric, isothionic, mucic, gentisic, isonicotinic, saccharic, glucuronic, furoic, glutamic, ascorbic, anthranilic, salicylic, phenylacetic, mandelic, embonic (pamoic), ethanesulfonic, pantothenic, stearic, sulfinilic, alginic and galacturonic acid;

and arylsulfonic, for example benzenesulfonic, p-toluenesulfonic, oxalic, methanesulfonic and naphthalenesulfonic acid

5. The compound of claim 4, wherein the acid is p-toluenesulfonic or oxalic.

6. The compound of claim 2, wherein the compound is an acid addition salt.

7. The compound of claim 5, wherein the acid is selected from succinic, maleic, acetic, fumaric, citric, tartaric, benzoic, trifluoroacetic, malic, lactic, formic, propionic, glycolic, gluconic, camphorsulfuric, isothionic, mucic, gentisic, isonicotinic, saccharic, glucuronic, furoic, glutamic, ascorbic, anthranilic, salicylic, phenylacetic, mandelic, embonic (pamoic), ethanesulfonic, pantothenic, stearic, sulfinilic, alginic and galacturonic acid;

and arylsulfonic, for example benzenesulfonic, p-toluenesulfonic, oxalic, methanesulfonic and naphthalenesulfonic acid

8. The compound of claim 6, wherein the acid is p-toluenesulfonic or oxalic.

9. A pharmaceutical composition comprising a compound of claim 1 and one or more pharmaceutically acceptable excipients, diluents or carriers.

10. The pharmaceutical composition according to claim 9, further comprising one or more active substances.

11. A pharmaceutical composition comprising a compound of claim 2 and one or more pharmaceutically acceptable excipients, diluents or carriers.

12. The pharmaceutical composition according to claim 11, further comprising one or more active substances.

13. A pharmaceutical composition comprising a compound of claim 3 and one or more pharmaceutically acceptable excipients, diluents or carriers.

14. A pharmaceutical composition comprising a compound of claim 6 and one or more pharmaceutically acceptable excipients, diluents or carriers.

15. A method of treating a histone demethylase-(HDME-) dependent disease in a subject, comprising administering to said subject a therapeutically effective amount of at least one compound of claim 1.

16. The method of claim 15, wherein the HDME-dependent disease is a proliferative or hyperproliferative disease.

17. The method of claim 15, wherein the HDME-dependent disease is a cancer.

18. A method of treating a histone demethylase-(HDME-) dependent disease in a subject, comprising administering to said subject a therapeutically effective amount of at least one compound of claim 2.

19. The method of claim 18, wherein the HDME-dependent disease is a proliferative or hyperproliferative disease.

20. The method of claim 19, wherein the HDME-dependent disease is a cancer.