Small molecule FIEL1 inhibitor in inflammatory and fibrotic lung injury
View Patent ↗Novel compounds are disclosed along with methods of inhibiting the TGFβ pathway and methods of treating Idiopathic Pulmonary Fibrosis (IPF) using such compounds.
1. A pharmaceutical formulation comprising 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;
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, and
a pharmaceutically acceptable excipient.
2. The pharmaceutical formulation 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.
3. The pharmaceutical formulation 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.
4. The pharmaceutical formulation of claim 1 , wherein R′ is H.
5. The pharmaceutical formulation of claim 1 , wherein R″ is H.
6. The pharmaceutical formulation of claim 1 , wherein R is
7. The pharmaceutical formulation of claim 1 , wherein R is
8. The pharmaceutical formulation of claim 1 , wherein R is
9. The pharmaceutical formulation of claim 1 , wherein R is