US 12,281,083 B2
2-substituted amino-naphth (1,2-d) imidazol-5-one compounds of pharmaceutically acceptable salts thereof
Hiroyuki Kitano, Osaka (JP); and Kazuto Mori, Osaka (JP)
Assigned to PTC Therapeutics, Inc., Warren, NJ (US)
Filed by PTC Therapeutics, Inc., Warren, NJ (US)
Filed on Jul. 11, 2022, as Appl. No. 17/862,290.
Application 17/862,290 is a continuation of application No. 16/989,582, filed on Aug. 10, 2020, granted, now 11,390,588.
Application 16/989,582 is a continuation of application No. 16/349,940, granted, now 10,738,014, issued on Aug. 11, 2020, previously published as PCT/US2017/061879, filed on Nov. 15, 2017.
Claims priority of application No. 2016-222028 (JP), filed on Nov. 15, 2016; and application No. 2016-250981 (JP), filed on Dec. 26, 2016.
Prior Publication US 2023/0116786 A1, Apr. 13, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 31/4184 (2006.01); A61K 31/422 (2006.01); A61K 31/427 (2006.01); A61K 31/4439 (2006.01); A61K 31/4709 (2006.01); A61K 31/538 (2006.01); A61P 3/10 (2006.01); A61P 25/00 (2006.01); A61P 25/16 (2006.01); C07D 233/88 (2006.01); C07D 235/02 (2006.01); C07D 401/04 (2006.01); C07D 401/14 (2006.01); C07D 403/04 (2006.01); C07D 403/10 (2006.01); C07D 403/14 (2006.01); C07D 405/04 (2006.01); C07D 407/04 (2006.01); C07D 413/04 (2006.01); C07D 413/10 (2006.01); C07D 413/14 (2006.01); C07D 417/04 (2006.01)
CPC C07D 233/88 (2013.01) [A61K 31/4184 (2013.01); A61K 31/422 (2013.01); A61K 31/427 (2013.01); A61K 31/4439 (2013.01); A61K 31/4709 (2013.01); A61K 31/538 (2013.01); A61P 3/10 (2018.01); A61P 25/00 (2018.01); A61P 25/16 (2018.01); C07D 235/02 (2013.01); C07D 401/04 (2013.01); C07D 401/14 (2013.01); C07D 403/04 (2013.01); C07D 403/10 (2013.01); C07D 403/14 (2013.01); C07D 405/04 (2013.01); C07D 407/04 (2013.01); C07D 413/04 (2013.01); C07D 413/10 (2013.01); C07D 413/14 (2013.01); C07D 417/04 (2013.01)] 18 Claims
 
1. A method of treating a disease caused by or aggravated by oxidative stress or mitochondrial dysfunction, comprising administering to a patient in need of the treatment and/or prevention a therapeutically effective amount of a compound according to formula (1):

OG Complex Work Unit Chemistry
or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein
R1 and R2 are each independently
(1) a hydrogen atom,
(2) an optionally substituted C1-6alkyl group, an optionally substituted C2-6alkenyl group, or an optionally substituted C2-6alkynyl group,
(3) an optionally substituted C3-10alicyclic hydrocarbon group (wherein the group may contain one or more unsaturated bonds),
(4) an optionally substituted, 3 to 8-membered heterocyclic group (wherein the group may contain one or more unsaturated bonds, and a carbon atom on the ring of the group is bonded with the nitrogen atom to which R1 and R2 are attached),
(5) an optionally substituted C6-10aryl group, or
(6) an optionally substituted, 5 to 12-membered monocyclic or polycyclic heteroaryl group (with the proviso that in the group, a carbon atom on its ring is bonded with the nitrogen atom to which R1 and R2 are attached), or
R1 and R2 are taken together with the nitrogen atom to which they are attached to form an optionally substituted, 3 to 8-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds), and
R3 is
(1) an optionally substituted C6-10aryl group, or
(2) an optionally substituted, 5 to 12-membered monocyclic or polycyclic heteroaryl group (with the proviso that in the group, a carbon atom on its ring is bonded with the carbon atom to which R3 is attached); or
administering a pharmaceutical composition comprising the therapeutically effective amount of the compound of formula (1) and a pharmaceutically acceptable carrier, to a patient in need of the treatment;
wherein the disease caused by or aggravated by oxidative stress or mitochondrial dysfunction is selected from the group consisting of: amyotrophic lateral sclerosis (ALS), Huntington disease, Parkinson disease, Friedreich ataxia (FRDA), Alzheimer disease, multiple system atrophy (MS), Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, atherosclerosis, myocardial infarction, cerebral infarction, diabetes, alcoholic liver injury, non-alcoholic steatohepatitis (NASH), pulmonary fibrosis, hearing loss, spinal muscular atrophy (SMA), chronic obstructive pulmonary disease, Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), Leigh Syndrome and Kearns-Sayre syndrome (KSS), chronic progressive external ophthalmoplegia (CPEO), myoclonic epilepsy with ragged-red fibers (Fukuhara disease, MERRF, myoclonic epilepsy, myoclonic epilepsy syndrome), Pearson's disease (pancytopenia, multiple organ dysfunction syndrome), senile cognition disorder, cancer, and aging-related disease.