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US 2022/0175754 A1Published application
P97 inhibitors for treating cancer and neurodegenerative disorders
AssigneeLundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
InventorTsui-Fen Chou
Life of this patent
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Abstract
The present disclosure relates generally to methods for treating multisystem degenerative diseases, hematological malignancies, solid tumors, and neurodegenerative disorders.
Claims20
A method of treating a multisystem degenerative disease or a neurodegenerative disorder, comprising administering to a patient in need of a compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
- Z is O, SO0-2, NR, C(R7)2, alkenyl or alkynyl;
- R2 and R3 are independently an optionally substituted C1-9 cyclic, C3-9 heterocyclic, or halogen, or R2 and R3 together form an optionally substituted C3-9 cyclic or 3- to 9-membered heterocyclic ring;
- R1 is optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl;
- R4 is H, C(R7)2, aryl, or heteroaryl;
- X is O or SO0-2;
- Y is an optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, or heterocycle;
- R5 is H, nitrile, an optionally substituted aryl, an optionally substituted heterocycle, optionally substituted C1-C6 alkyl, optionally substituted C3-C9 cycloalkyl, or
- where
- R′ and R″ are each independently selected from the group consisting of H, optionally substituted alkyl, —OR, halogen, —N(R)2, and optionally substituted cycloalkyl or heterocycle;
- or R′ and R″ may together form a 3- to 6-membered cycloalkyl or heterocycle that is optionally substituted;
- D′ is selected from the group consisting of —O—, —NR—, —OCONR—, —NRSO2—, —NRCO—, —NRSO2NR—, —NRCOO—, —NRCONR—, and —NRC(NR)NR—;
- E′ is selected from a bond or an optionally substituted C1-C6 alkyl and cycloalkyl;
- and
- F′ is selected from the group consisting of H, an optionally substituted cycloalkyl, an optionally substituted heterocycle, an optionally substituted aryl, and an optionally substituted heteroaryl;
- R is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted cycloalkyl;
- and
- R7 is selected from the group consisting of H, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, —OR, and —N(R)2.
15 more elements
A method of treating a hematological malignancy, comprising administering to a patient in need of a compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
- Z is O, SO0-2, NR, C(R7)2, alkenyl or alkynyl;
- R2 and R3 are independently an optionally substituted C1-9 cyclic, C3-9 heterocyclic, or halogen, or R2 and R3 together form an optionally substituted C3-9 cyclic or 3- to 9-membered heterocyclic ring;
- R1 is optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl;
- R4 is H, C(R7)2, aryl, or heteroaryl;
- X is O or SO0-2;
- Y is an optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, or heterocycle;
- R5 is H, nitrile, an optionally substituted aryl, an optionally substituted heterocycle, optionally substituted C1-C6 alkyl, optionally substituted C3-C9 cycloalkyl, or
- where
- R′ and R″ are each independently selected from the group consisting of H, optionally substituted alkyl, —OR, halogen, —N(R)2, and optionally substituted cycloalkyl or heterocycle;
- or R′ and R″ may together form a 3- to 6-membered cycloalkyl or heterocycle that is optionally substituted;
- D′ is selected from the group consisting of —O—, —NR—, —OCONR—, —NRSO2—, —NRCO—, —NRSO2NR—, —NRCOO—, —NRCONR—, and —NRC(NR)NR—;
- E′ is selected from a bond or an optionally substituted C1-C6 alkyl and cycloalkyl;
- and
- F′ is selected from the group consisting of H, an optionally substituted cycloalkyl, an optionally substituted heterocycle, an optionally substituted aryl, and an optionally substituted heteroaryl;
- R is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted cycloalkyl;
- and
- R7 is selected from the group consisting of H, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, —OR, and —N(R)2.
15 more elements
A method of treating a cancer, comprising administering to a patient in need of a compound of Formula (I):
- or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
- Z is O, SO0-2, NR, C(R7)2, alkenyl or alkynyl;
- R2 and R3 are independently an optionally substituted C1-9 cyclic, C3-9 heterocyclic, or halogen, or R2 and R3 together form an optionally substituted C3-9 cyclic or 3- to 9-membered heterocyclic ring;
- R1 is optionally substituted phenyl or an optionally substituted 5- or 6-membered heteroaryl;
- R4 is H, C(R7)2, aryl, or heteroaryl;
- X is O or SO0-2;
- Y is an optionally substituted alkyl, alkenyl, aryl, heteroaryl, cycloalkyl, or heterocycle;
- R5 is H, nitrile, an optionally substituted aryl, an optionally substituted heterocycle, optionally substituted C1-C6 alkyl, optionally substituted C3-C9 cycloalkyl, or
- where
- R′ and R″ are each independently selected from the group consisting of H, optionally substituted alkyl, —OR, halogen, —N(R)2, and optionally substituted cycloalkyl or heterocycle;
- or R′ and R″ may together form a 3- to 6-membered cycloalkyl or heterocycle that is optionally substituted;
- D′ is selected from the group consisting of —O—, —NR—, —OCONR—, —NRSO2—, —NRCO—, —NRSO2NR—, —NRCOO—, —NRCONR—, and —NRC(NR)NR—;
- E′ is selected from a bond or an optionally substituted C1-C6 alkyl and cycloalkyl;
- and
- F′ is selected from the group consisting of H, an optionally substituted cycloalkyl, an optionally substituted heterocycle, an optionally substituted aryl, and an optionally substituted heteroaryl;
- R is selected from the group consisting of H, optionally substituted alkyl, and optionally substituted cycloalkyl;
- and
- R7 is selected from the group consisting of H, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, —OR, and —N(R)2.
15 more elements
Dependencies are inferred from the claim text.