Back to results
US 10,894,782 B2Granted
Modulators of P97 AAA ATPase activity
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsDonna M. Huryn, Peter Wipf, Matthew G. LaPorte
Life of this patent
Estimating the term…
Abstract
The present invention is directed to methods of inhibiting or modulating p97 and compounds and compositions useful in such methods. Diseases and conditions that can be treated with the compounds and compositions of the invention include, but are not limited to, cancer and neurodegenerative disorders susceptible to treatment by modulation or inhibition of p97.
Claims26
A compound having a structure 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 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 or cycloalkyl;
- 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.
14 more elements
A compound having a structure of formula (II):
- or a pharmaceutically acceptable salt, solvate or prodrug thereof, wherein:
- X is O, SO0-2, or NR;
- Y is optionally substituted alkyl, optionally substituted alkenyl, alkynyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted cycloalkyl, or optionally substituted non-aromatic heterocyclic;
- Y′ is alkynyl, optionally substituted heteroaryl, or optionally substituted non-aromatic heterocyclic;
- R2 and R3 are independently optionally substituted C1-6 alkyl, optionally substituted C1-9 cyclic, optionally substituted C3-9 heterocyclic, or halogen, or R2 and R3 together form an optionally substituted C3-9 cyclic or optionally substituted 3- to 9-membered heterocyclic ring;
- Z is O, SO0-2, NR, C(R7)2, alkenyl or alkynyl;
- R1 is optionally substituted phenyl, optionally substituted 5- or 6-membered heteroaryl, or optionally substituted non-aromatic heterocyclic;
- R4 is H, C(R7)2, aryl, or heteroaryl;
- 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, optionally substituted cycloalkyl, and optionally substituted heterocycle;
- or R′ and R″ may together form an optionally substituted 3- to 6-membered cycloalkyl or optionally substituted 3- to 6-membered heterocycle;
- D′ is selected from the group consisting of —O—, —NR—, —OCONR—, —OCO—, —NRSO2—, —NRCO—, —NRSO2NR—, —NRCOO—, —NRCONR—, and —NRC(NR)NR—;
- E′ is selected from the group consisting of a bond, an optionally substituted C1-C6 alkyl, optionally substituted C1-C6 alkenyl, and optionally substituted cycloalkyl;
- and
- F′ is selected from the group consisting of H, an optionally substituted cycloalkyl, an optionally substituted non-aromatic heterocycle, an optionally substituted aryl, and an optionally substituted heteroaryl;
- R is independently selected from the group consisting of H, optionally substituted alkyl, and optionally substituted cycloalkyl;
- and
- R7 is independently selected from the group consisting of H, halogen, optionally substituted alkyl, optionally substituted cycloalkyl, —OR, and —N(R)2.
16 more elements
Dependencies are inferred from the claim text.