Pantothenate derivatives for the treatment of neurologic disorders
View Patent ↗The present disclosure relates to pantothenate derivatives for the treatment of neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment of neurologic disorders.
1. A method of treating pantothenate kinase-associated neurodegeneration in a subject,
the method comprising administering to the subject an effective amount of a compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein R, R′ and R″ are selected from the group consisting of:
R (Amino Acid)
R′
R″
Me (L-Ala)
Me
Me
Me (L-Ala)
Et
Bn
Me (L-Ala)
MeCyPr
MeCyPr
MeIndole (L-Trp)
Bn
Et.
2. The method of claim 1 , wherein R, R′ and R″ are methyl.
3. The method of claim 1 , wherein R is methyl, R′ is ethyl and R″ is benzyl.
4. The method of claim 1 , wherein R is methyl, and R′ and R″ are methylcyclopropyl.
5. The method of claim 1 , wherein R is 1H-indol-3yl-methyl, R′ is benzyl and R″ is ethyl.
6. The method of claim 1 , wherein the subject is a child.
7. The method of claim 6 , wherein the child is 10 to 15 years old.
8. The method of claim 1 , wherein the subject is an adult.
9. A method of treating a subject having neuronal cells with an over accumulation of iron, the method comprising administering to the subject an effective amount of a compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein R, R′ and R″ are selected from the group consisting of:
R (Amino Acid)
R′
R″
Me (L-Ala)
Me
Me
Me (L-Ala)
Et
Bn
Me (L-Ala)
MeCyPr
MeCyPr
MeIndole (L-Trp)
Bn
Et.
10. The method of claim 9 , wherein R, R′ and R″ are methyl.
11. The method of claim 9 , wherein R is methyl, R′ is ethyl and R″ is benzyl.
12. The method of claim 9 , wherein R is methyl, and R′ and R″ are methylcyclopropyl.
13. The method of claim 9 , where R is 1H-indol-3yl-methyl, R′ is benzyl and R″ is ethyl.
14. The method of claim 9 , wherein the subject is a child.
15. The method of claim 14 , wherein the child is 10 to 15 years old.
16. The method of claim 9 , wherein the subject is an adult.
17. The method of claim 9 , wherein the subject suffers from pantothenate kinase-associated neurodegeneration.
18. A method of treating Parkinson's disease, dystonia, extrapyramidal effects, dysphagia, rigidity and/or stiffness of limbs, choreoathetosis, tremor, spasticity, muscle weakness, or seizure in a subject, the method comprising administering to the subject an effective amount of a compound of the following formula:
or a pharmaceutically acceptable salt thereof, wherein R, R′ and R″ are selected from the group consisting of:
R (Amino Acid)
R′
R″
Me (L-Ala)
Me
Me
Me (L-Ala)
Et
Bn
Me (L-Ala)
MeCyPr
MeCyPr
MeIndole (L-Trp)
Bn
Et.
19. The method of claim 18 , wherein R, R′ and R″ are methyl.