US 11,945,787 B2Granted

Substituted imidazoles for preventing and/or treating cell or tissue necrosis

AssigneeEla Pharma Ltd.

InventorsIlana Nathan, Boris Khalfin

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Abstract

Inhibitor compounds and agents of Cathepsin C, CELA1, CELA3A and/or structurally related molecules thereto, compositions comprising the same, and uses thereof in the inhibition and/or prevention of cell and/or tissue necrosis are described. The compounds include imidazoles of Formula VI: wherein G1 is pyrrolidine, pyrazolidine, imidazolidine piperidine, or piperazine and G2 is alkyl, cycloalkyl, heterocycle, or aryl. The pyrrolidine, pyrazolidine, imidazolidine, piperidine, or piperazine of G1 and the alkyl, cycloalkyl, heterocycle, or aryl of G2 are optionally substituted with one or more substituents independently selected from the group consisting of halogen, NO2, CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, OH, OC1-C6 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)NH2, C(O)OH, and C(O)OC1-C6 alkyl. Variations applications for the described compounds, and combination therapies are further described as well.

Claims16

Dependent claims

A method for ameliorating, inhibiting, or reducing the incidence of necrotic cell death in a subject in need thereof, wherein the method comprises administering to the subject a therapeutically effective amount of a compound of Formula VI:

or a pharmaceutically acceptable salt thereof,
wherein:
G1 is pyrrolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, or piperazinyl, wherein the pyrrolidinyl, pyrazolidinyl, imidazolidinyl, piperidinyl, or piperazinyl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, NO2, CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, OH, OC1-C6 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)NH2, C(O)OH, and C(O)OC1-C6 alkyl;
and
G2 is alkyl, cycloalkyl, heterocyclyl, or aryl, wherein the alkyl, cycloalkyl, heterocyclyl, or aryl is optionally substituted with one or more substituents independently selected from the group consisting of halogen, NO2, CN, C1-C6 alkyl, C1-C6 haloalkyl, NH2, OH, OC1-C6 alkyl, C(O)H, C(O)C1-C6 alkyl, C(O)NH2, C(O)OH, and C(O)OC1-C6 alkyl;
wherein the subject suffers from cellular necrosis of a cell selected from the group consisting of a bone cell, a brain cell, a cardiac cell, a cartilage cell, an embryonic cell, an epidermal cell, an epithelial cell, a fibroblast, a gastrointestinal cell, a glial cell, a gonadal cell, a hematopoetic cell, a kidney cell, a liver cell, a lung cell, a lymphocyte, a macrophage, a muscle cell, a neuronal cell, a pancreatic cell, a parenchymal cell, a retinal cell, a spleen cell, and a stem cell.

3 more elements

Dependencies are inferred from the claim text.

Facts

Application: 17/201,201Filed 15 Mar 2021 · division
Priority: 7 Apr 2015
Published: US 2021/0309620 A17 Oct 2021
Granted: 2 Apr 2024
Term ends: Not estimatedThe source records don’t support an estimate.

Classification36 codes

C07D 265/22
With hetero atoms directly attached in position 4: oxygen atoms
A61K 31/00
Medicinal preparations containing organic active ingredients
A61K 31/167
Having aromatic rings, e.g. colchicine, atenolol, progabide: having the nitrogen of a carboxamide group directly attached to the aromatic ring,…
A61K 31/4045
Indoles, e.g. pindolol: indole-alkylamines; Amides thereof, e.g. serotonin, melatonin

Family

Application62/143,821Us provisional application · filed 7 Apr 2015
Application62/170,717Us provisional application · filed 4 Jun 2015
PCT/IL2016/050371Parent of this division · filed 7 Apr 2016
US 2021/0309620 A1Pre-grant publication · published 7 Oct 2021
Application15/564,836Parent of this division
US 10,968,185 B2Parent of this division
US 2018/0312477 A1Published application
US 11,945,787 B2This patent

From the US filing history. Foreign family members aren’t listed.