Histone demethylase inhibitors

• US 9,994,562 B2
• Filed: 03/12/2014
• Issued: 06/12/2018
• Est. Priority Date: 03/15/2013
• Status: Active Grant

• Current Assignee: Celgene Quanticel Research, Inc. (Bristol-Myers Squibb Company)
• Original Assignee: Celgene Quanticel Research, Inc. (Bristol-Myers Squibb Company)
• Inventors: Kanouni, Toufike, Stafford, Jeffrey Alan, Veal, James Marvin, Wallace, Michael Brennan
• Primary Examiner(s): Sznaidman, Marcos L
• Application Number:
  US14/774,335
• Publication Number:
  US 20160039808A1
• Time in Patent Office: 1,553 Days
• Field of Search: 5142342
• 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 471/04 Ortho-condensed systems

Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyrido[3,4-d]pyrimidin-4-one derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of 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.

Claims

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

2. The compound of claim 1, wherein the heteroaryl group is substituted with at least one halogen substituent.

3. The compound of claim 1, wherein the heteroaryl group is substituted with at least one alkyl substituent.

4. The compound of claim 1, wherein the heteroaryl group is substituted with at least one group selected from hydroxy, alkoxy, aryloxy, amino, alkylamino, arylamino, or diakylamino.

5. The compound of claim 1, wherein the heteroaryl group is substituted with at least one group selected from —

NHCOR³, —

NHCO₂R³, —

NHCONHR³, —

N(R⁴)COR³, —

N(R⁴)CO₂R³, —

N(R⁴)CONHR³, —

N(R⁴)CON(R⁴)R³, —

NHSO₂R³, or —

NR⁴SO₂R³, wherein each R³ is independently selected from alkyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl, and each R⁴ is an alkyl.

6. The compound of claim 1, wherein the heteroaryl group is substituted with at least one group selected from —

CONH₂, —

CONHR³, —

CON(R³)₂, —

COR³, —

SO₂NH₂, —

SO₂NHR³, —

O₂N(R³)₂,or —

SO₂R³, wherein each R³ is independently selected from alkyl, aryl, heteroaryl, carbocyclyl, or heterocyclyl.

7. The compound of claim 1, wherein the heteroaryl group is substituted with a group selected from aryl, heteroaryl, carbocyclyl, or heterocyclyl.

8. The compound of claim 1, wherein the heteroaryl is a pyrazolyl having the structure

9. The compound of claim 8, wherein the R⁵ group is a C1-C6 alkyl, optionally substituted with at least one group selected from hydroxy, C1-C4 alkoxy, amino, C1-C4 alkylamino, C1-C4 diakylamino, piperdinyl, pyrrolidnyl, or morpholinyl.

10. The compound of claim 8, wherein the R⁵ group is a heterocyclyl selected from 4-tetrahydropyranyl, 1-morpholinyl, or 4-piperdinyl having the structure

11. A pharmaceutical composition comprising the compound of claim 1, or pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.