Pantetheine derivatives for the treatment of neurologic disorders
AssigneeRetrophin, Inc.
InventorsMaria Beconi, Daniel Elbaum, Savina Malancona
Life of this patent
Estimating the term…
Abstract
Compounds having the following formula (I): Formula I and pharmaceutically acceptable salts thereof, wherein A, B, D, E and R1 are as defined herein, are provided. Methods comprising the use of such compounds for the treatment of neurological disorders, such as pantothenate kinase-associated neurodegeneration, and pharmaceutical compositions containing such compounds, and their use in the treatment of neurological disorders, also are provided.
Claims29
A compound having the following structure (I):
- or a pharmaceutically acceptable salt thereof, wherein:
- E is O or NR2;
- D is absent, C1-C3 alkylene, C(O)O(alkylene) or aryl, wherein each of said C1-C3 alkylene, C(O)O(alkylene) and aryl is unsubstituted or substituted with R3;
- B is absent, C1-C3 alkylene, C3-C6 cycloalkylene, (C1-C3 alkylene)NR2, C(O)NR2(alkylene), aryl, heteroaryl or heterocyclyl, wherein each of said C1-C3 alkylene, C3-C6 cycloalkylene, C(O)NR2(alkylene), aryl, heteroaryl and heterocyclyl is unsubstituted or substituted with R6;
- A is absent, H, OR5, R5C(O), R5OC(O), R5OC(O)O, R5C(O)O, R5C(O)S, NR2R5C(O), NR2R5C(O)O, R5C(O)NR2, C(O)ONR2, S(O)NR2, R5SO2NR2, NR2R5, C1-C6 alkyl, C3-C6 cycloalkyl, heterocyclyl, aryl or heteroaryl, wherein each of said C1-C6 alkyl, C3-C6 cycloalkyl, heterocyclyl, aryl and heteroaryl is unsubstituted or substituted with R6;
- R1 is H, C1-C6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, C3-C6 cycloalkyl, or cycloalkylalkyl, wherein each of said C1-C6 alkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, C3-C6 cycloalkyl, and cycloalkylalkyl is unsubstituted or substituted with R6;
- R2 is H or C1-C6 alkyl;
- R3 is H, C1-C6 alkyl, hydroxy, amino, arylalkyl, heteroarylalkyl or C3-C6 cycloalkyl, wherein each of said C1-C6 alkyl, arylalkyl, heteroarylalkyl and C3-C6 cycloalkyl is unsubstituted or substituted with R4;
- R4 is C1-C6 alkyl, C1-C6 alkoxy, hydroxy or amino;
- R5 is H, C1-C6 alkyl, C1-C6 alkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, C3-C6 cycloalkyl, cycloalkylalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl or dialkylaminoalkyl, wherein each of said C1-C6 alkyl, C1-C6 alkoxy, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, amino, alkylamino, dialkylamino, aminoalkyl, alkylaminoalkyl and dialkylaminoalkyl is unsubstituted or substituted with R6;
- R6 is C1-C6 alkyl, C1-C6 alkoxy, hydroxyl, amino, halo, oxo, CN, NO2, SF5, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, C3-C6 cycloalkyl, C3-C4 spiro-substituted cycloalkyl, cycloalkylalkyl, SO2R7, R7C(O), R7C(O)NR2 or C(O)OR8, wherein each of said C1-C6 alkyl, C1-C6 alkoxy, heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, C3-C6 cycloalkyl, C3-C4 spiro-substituted cycloalkyl and cycloalkylalkyl is unsubstituted or substituted with R7;
- R7 is C1-C6 alkyl, C1-C6 alkoxy, hydroxyl, halo, oxo, CN, NO2, SF5, amino, alkylamino or dialkylamino;
- and
- R8 is H, C1-C6 alkyl or arylalkyl;
- or
- D is absent, and A, B, and E together form a 6-membered heterocyclic or heteroaryl ring, wherein said heterocyclic or heteroaryl ring is unsubstituted or substituted with R6.
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Dependencies are inferred from the claim text.