Small molecule FIEL1 inhibitor in inflammatory and fibrotic lung injury

Patent metadata

Field	Value
Publication number	US-10968183-B2
Application number	US-201916435284-A
Country	US
Kind code	B2
Filing date	Jun 7, 2019
Priority date	Apr 22, 2015
Publication date	Apr 6, 2021
Grant date	Apr 6, 2021

Abstract

Novel compounds are disclosed along with methods of inhibiting the TGFβ pathway and methods of treating Idiopathic Pulmonary Fibrosis (IPF) using such compounds.

First claim

What is claimed is:

1. A method of treating a disease associated with an activated inflammatory pathway selected from a NF-kB, TGFβ and JAK/STAT pathway, the disease selected from pulmonary fibrosis, inflammatory bowel disease, and colitis, the method comprising administering to a subject in need thereof a therapeutically effective amount of a compound represented by Formula (I):

wherein:
R is

and
wherein:
W is selected from the group consisting of H, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocyclic, halogen, amino, and hydroxy;
X is selected from the group consisting of H, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted cycloalkyl, optionally substituted heterocyclic, halogen, amino, and hydroxy;
Y is selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, and optionally substituted heterocyclic;
Z is selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, and optionally substituted heterocyclic, and wherein Y and Z optionally bind together to form a ring;
R′ is selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, and optionally substituted heterocyclic;
R″ is independently selected from the group consisting of H, optionally substituted alkyl, optionally substituted aryl, optionally substituted cycloalkyl, and optionally substituted heterocyclic; and
wherein one or more of the alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more C 1 -C 6 alkoxy, halogen or deuterium,
or a pharmaceutically acceptable salt thereof,
wherein the compound is capable of inhibiting NF-kB, TGFβ and/or JAK/STAT pathways, and
wherein the compound binds to FIEL1.

2. The method of claim 1 , wherein the therapeutically effective amount is about 0.1 to about 20 mg/kg/d.

3. The method of claim 1 , wherein the administration is oral, inhalation, intravenous, or intramuscular.

4. The method of claim 1 , wherein:
(a) W is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted aryl;
(b) X is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted aryl, and
(c) W and X cannot both be H.

5. The method of claim 1 , wherein:
(a) Y is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted aryl,
(b) Z is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted aryl, and
(c) Y and Z cannot both be H.

6. The method of claim 1 , wherein R′ is H.

7. The method of claim 1 , wherein R″ is H.

8. The method of claim 1 , wherein R is:

Assignees

• Univ Of Pittsburgh—Of The Commonwealth System Of Higher Education

Inventors

• Chen Beibei

Classifications

• A61P11/06

  Antiasthmatics · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/4184

  condensed with carbocyclic rings, e.g. benzimidazoles · CPC title

• C07D235/26 Primary

  Oxygen atoms · CPC title