2-substituted amino-naphth (1,2-d) imidazol-5-one compounds of pharmaceutically acceptable salts thereof

Inventors

Kitano, Hiroyuki • MORI, Kazuto

Assignees

PTC Therapeutics Inc

Abstract

Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotropic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.

Core Innovation

The invention relates to a method of treating and/or preventing diseases caused by or aggravated by oxidative stress or mitochondrial dysfunction by administering to a patient in need of treatment and/or prevention a therapeutically effective amount of a compound according to formula (1), or a reduced form thereof, or a pharmaceutically acceptable salt thereof. The method includes administration via a pharmaceutical composition comprising the therapeutically effective amount and a pharmaceutically acceptable carrier. The compounds are defined by substituent groups R1, R2, and R3 within the structural rules of formula (1).

R1 and R2 are each independently hydrogen, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C3-10 alicyclic hydrocarbon group, an optionally substituted 3 to 8-membered heterocyclic group, an optionally substituted C6-10 aryl group, or an optionally substituted 5 to 12-membered monocyclic or polycyclic heteroaryl group, or R1 and R2 together with the nitrogen atom form an optionally substituted 3 to 8-membered nitrogen-containing heterocycle, optionally containing one or more unsaturated bonds and optionally substituted with a C1-6 alkyl group. The connection rules for the ring carbon bonded to the nitrogen are explicitly included.

R3 is defined as an optionally substituted C6-10 aryl group or an optionally substituted 5 to 12-membered monocyclic or polycyclic heteroaryl group, with a proviso relating to ring bonding between a carbon atom on its ring and the carbon atom to which R3 is attached. The disclosed compound selections include specifically named 5H-naphth[1,2-d]imidazol-5-one derivatives and related benzonitrile/naphthalimidazole compounds, together with reduced forms of the scaffold and pharmaceutically acceptable salts.

Claims Coverage

The independent claim is a treatment method with one central inventive concept: administering a therapeutically effective amount of a defined compound family (formula (1), reduced form, or pharmaceutically acceptable salt) to treat diseases caused by or aggravated by oxidative stress or mitochondrial dysfunction. Dependent claims refine the compound structure by constraining R1/R2, including ring formation with nitrogen, and by defining R3 as an aryl/heteroaryl group with size and attachment rules.

Coverage centers on administering formula (1) compounds, or reduced forms or pharmaceutically acceptable salts, for diseases caused by or aggravated by oxidative stress or mitochondrial dysfunction. The inventive features are the treatment method, the nitrogen-containing heterocycle formed by R1/R2, the R3 aryl/heteroaryl attachment rules, and the selected named derivative compounds.

Stated Advantages

Documented Applications