Histone demethylase inhibitors

Patent metadata

Field	Value
Publication number	US-11214542-B2
Application number	US-202017024842-A
Country	US
Kind code	B2
Filing date	Sep 18, 2020
Priority date	Dec 21, 2012
Publication date	Jan 4, 2022
Grant date	Jan 4, 2022

Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

First claim

We claim:

1. A compound of Formula (XIa), or a pharmaceutically acceptable salt thereof,

wherein,
R 1 is hydrogen, methyl, or —OH;
each R 4 is independently hydrogen, fluoro, or methyl; and
R 5 , R 6 , R 7 and R 8 are each independently chosen from hydrogen, halogen, —OH, —CN, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted C 3 -C 7 carbocyclyloxy, optionally substituted C 4 -C 12 carbocyclylalkyl, optionally substituted C 4 -C 12 carbocyclylalkoxy, optionally substituted C 1 -C 6 alkynyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 aryl-S—, optionally substituted C 7 -C 14 aralkoxy, optionally substituted heteroaryl, and optionally substituted heteroaryloxy.

2. The compound or pharmaceutically acceptable salt of claim 1 , wherein each R 4 is hydrogen.

3. The compound or pharmaceutically acceptable salt of claim 1 , wherein each R 4 is fluoro.

4. The compound or pharmaceutically acceptable salt of claim 1 , wherein each R 4 is methyl.

5. The compound or pharmaceutically acceptable salt of claim 1 , wherein one R 4 is hydrogen.

6. The compound or pharmaceutically acceptable salt of claim 1 , wherein one R 4 is fluoro.

7. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 is hydrogen.

8. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 5 is hydrogen.

9. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 6 is hydrogen.

10. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 7 is hydrogen.

11. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 8 is hydrogen.

12. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 5 and R 7 are hydrogen.

13. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 5 and R 8 are hydrogen.

14. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 7 and R 8 are hydrogen.

15. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 6 is not hydrogen.

16. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 6 is chosen from optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted C 3 -C 7 carbocyclyloxy, optionally substituted C 4 -C 12 carbocyclylalkyl, optionally substituted C 4 -C 12 carbocyclylalkoxy, optionally substituted C 1 -C 6 alkynyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 aryl-S—, optionally substituted C 7 -C 14 aralkoxy, optionally substituted heteroaryl, and optionally substituted heteroaryloxy.

17. A pharmaceutical composition comprising a pharmaceutical acceptable carrier and a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

Assignees

• Celgene Quanticel Res Inc

Inventors

• Chen Young K
• Kanouni Toufike
• Nie Zhe
• Stafford Jeffrey Alan
• Veal James Marvin
• Wallace Michael Brennan

Classifications

• C07D405/14 Primary

  containing three or more hetero rings · CPC title

• C07D213/79 Primary

  Acids; Esters · CPC title

• C07D213/81

  Amides; Imides · CPC title

• C07D409/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D237/24

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title