Inhibitors of bromodomain-containing protein 4 (BRD4)

Patent metadata

Field	Value
Publication number	US-11117865-B2
Application number	US-201916442526-A
Country	US
Kind code	B2
Filing date	Jun 16, 2019
Priority date	Dec 16, 2016
Publication date	Sep 14, 2021
Grant date	Sep 14, 2021

Abstract

Certain embodiments are directed to small molecule selective inhibitors of the BRD4 bromodomain. Compounds described herein can be used to modulate the bronchiolar NFkB-BRD4 axis, which plays a role in acute neutrophilic response to viral molecular patterns. Compounds described herein can be developed as preventive and therapeutic agents for various human diseases and conditions.

First claim

The invention claimed is:

1. A compound, or a pharmaceutically acceptable salt thereof, having Formula III:

wherein:
R 11 , R 12 , and R 13 are independently H, —OH, halogen, alkoxy, —NH 2 , —CF 3 , —(CO)R 17 where R 17 is alkyl, alkoxy, amino, or alkylamino;
R 14 is a C1-4 alkyl substituted with one or more of OH, alkoxy, amino, alkylamino, or an unsubstituted 5-6 membered heterocycle with 1-3 heteroatoms.

2. The compound of claim 1 , wherein the compound is selected from compound having a structure of

3. The compound of claim 2 , wherein the compound has a structure of;

4. A compound, or a pharmaceutically acceptable salt thereof, having the Formula IIIa:

wherein:
R 11 , R 12 , and R 13 are independently H, —OH, halogen, alkoxy, —NH 2 , —CF 3 , —(CO)R 17 where R 17 is alkyl, alkoxy, amino, or alkylamino;
R 15 is H, —OH, alkyl, or NH 2 ;
p is 0-4;
R 16 is H, —OH, alkyl, alkoxy; or —NR 18 R 19 where R 18 and R 19 are independently H, alkyl; or R 18 and R 19 are optionally joined to form a 3-6 membered substituted or unsubstituted heterocycle having 1-3 heteroatoms;
wherein at least one of R 11 , R 12 , or R 13 is —OH, halogen, alkoxy, —NH 2 , —CF 3 , —(CO)R 17 when R 15 is H, and R 16 is H or alkyl.

Assignees

• Zhou Jia
• Brasier Allan R
• Tian Bing
• Liu Zhiqing
• Chen Haiying
• Rytting Erik
• Univ Texas

Inventors

• Zhou Jia
• Brasier Allan R
• Tian Bing
• Liu Zhiqing
• Chen Haiying
• Rytting Erik

Classifications

• C07D413/14

  containing three or more hetero rings · CPC title

• C07D413/04

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D207/08

  with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms · CPC title

• C07D401/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07C311/37

  having the sulfur atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring · CPC title