Small molecule modulators of pantothenate kinases

Patent metadata

Field	Value
Publication number	US-12545663-B2
Application number	US-202318390494-A
Country	US
Kind code	B2
Filing date	Dec 20, 2023
Priority date	Dec 27, 2017
Publication date	Feb 10, 2026
Grant date	Feb 10, 2026

Abstract

The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

First claim

What is claimed is:

1 . A method of modulating pantothenate kinase activity in a cell, the method comprising contacting at least one cell with an effective amount of a compound of the formula

or a pharmaceutically acceptable salt thereof.

2 . The method of claim 1 , wherein modulating is inhibiting.

3 . The method of claim 2 , wherein the cell is involved in a pathology characterized by heteromorphism of a gene associated with pantothenate kinase enzyme.

4 . The method of claim 2 , wherein the cell is involved in a pathology characterized by misregulation of expression of a gene associated with pantothenate kinase enzyme.

5 . The method of claim 1 , wherein modulating is activating.

6 . The method of claim 5 , wherein the cell is involved in a pathology characterized by heteromorphism of a gene associated with pantothenate kinase enzyme.

7 . The method of claim 5 , wherein the cell is involved in a pathology characterized by misregulation of expression of a gene associated with pantothenate kinase enzyme.

8 . A method of therapeutically treating a disorder associated with pantothenate kinase activity in a subject, the method comprising administering to the subject an effective amount of a compound of the formula

or a pharmaceutically acceptable salt thereof.

9 . The method of claim 8 , further comprising administering to the subject an effective amount of pantothenate and/or pantothenic acid.

10 . The method of claim 8 , wherein the disorder associated with pantothenate kinase activity is hyperglycemia caused by misregulated and/or elevated coenzyme A.

11 . The method of claim 8 , wherein the disorder associated with pantothenate kinase activity is neurodegeneration caused by a deficiency of pantothenate kinase or coenzyme A.

12 . The method of claim 8 , wherein the disorder associated with pantothenate kinase activity is neurodegeneration characterized by brain iron accumulation or neurological disorder characterized by reduced mitochondrial function.

13 . The method of claim 8 , wherein the disorder associated with pantothenate kinase activity is selected from dystonia, extrapyramidal effects, dysphagia, muscle rigidity and/or limb stiffness, choreoathetosis, tremor, dementia, spasticity, muscle weakness, or seizure.

14 . The method of claim 11 , wherein the neurodegeneration is pantothenate kinase-associated neurodegeneration (PKAN).

Assignees

• St Jude Childrens Res Hospital Inc

Inventors

• Lee Richard E
• Tangallapally Rajendra P
• Rock Charles O
• Jackowski Suzanne
• Edwards Anne V
• Yun Mi Kyung
• Subramanian Chitra
• Zamboni Robert
• Reddy T Jagadeeswar

Classifications

• A61K31/197

  the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid (carnitine A61K31/205) · CPC title

• C07D403/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D237/20

  Nitrogen atoms (nitro radicals C07D237/12) · CPC title

• A61P25/28

  for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia · CPC title

• A61K31/501

  not condensed and containing further heterocyclic rings · CPC title