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US 11,639,325 B2Granted
Compositions of polyhydroxylated benzophenones and methods of treatment of neurodegenerative disorders
AssigneesMassachusetts Institute of Technology, The General Hospital Corporation
InventorsLi-Huei Tsai, Stephen J. Haggarty, Debasis Patnaik, Ping-Chieh Pao
Life of this patent
Estimating the term…
Abstract
The present invention relates to polyhydroxylated benzophenone compounds useful in the treatment of neurodegenerative, neurological, psychiatric, and cognitive diseases, in particular those associated with a deficiency in HDAC1 deacetylase activity.
Claims42
A prodrug of a compound of formula I:
- or a pharmaceutically acceptable salt, hydrate, solvate, or tautomer thereof, wherein:
- R1, R2, R3, R4, R5 and R6 are each independently H, PO(ORx)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3 to 8-membered heterocyclyl, aryl, heteroaryl, CO(C1-C6 alkyl), CO(C2-C6 alkenyl), CO(C2-C6 alkynyl), CO(C3-C8 cycloalkyl), CO(3 to 8-membered heterocyclyl), CO(aryl), CO(heteroaryl), CON(Ry)2, COO(C1-C6 alkyl), COO(C2-C6 alkenyl), COO(C2-C6 alkynyl), COO(C3-C8 cycloalkyl), COO(3 to 8-membered heterocyclyl), or COO(aryl), COO(heteroaryl) wherein each PO(ORx)2, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3 to 8-membered heterocyclyl, aryl, heteroaryl, CO(C1-C6 alkyl), CO(C2-C6 alkenyl), CO(C2-C6 alkynyl), CO(C3-C8 cycloalkyl), CO(3 to 8-membered heterocyclyl), CO(aryl), CO(heteroaryl), CON(Ry)2, COO(C1-C6 alkyl), COO(C2-C6 alkenyl), COO(C2-C6 alkynyl), COO(C3-C8 cycloalkyl), COO(3 to 8-membered heterocyclyl), COO(aryl) or COO(heteroaryl) is optionally substituted with one or more substituents selected from the group consisting of halogen, OH, NH2, CN, C1-C6 alkyl, aryl, heteroaryl and C1-C6 alkoxy;
- Rx is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3 to 8-membered heterocyclyl, aryl, heteroaryl, CO(C1-C6 alkyl), CO(C2-C6 alkenyl), CO(C2-C6 alkynyl), CO(C3-C8 cycloalkyl), CO(3 to 8-membered heterocyclyl), CO(aryl), or CO(heteroaryl) wherein each C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3 to 8-membered heterocyclyl, aryl, heteroaryl, CO(C1-C6 alkyl), CO(C2-C6 alkenyl), CO(C2-C6 alkynyl), CO(C3-C8 cycloalkyl), CO(3 to 8-membered heterocyclyl), CO(aryl), or CO(heteroaryl) is optionally substituted with one or more substituents selected from the group consisting of halogen, OH, NH2, CN, C1-C6 alkyl, aryl, heteroaryl and C1-C6 alkoxy;
- Ry is independently H, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3 to 8-membered heterocyclyl, aryl, heteroaryl, CO(C1-C6 alkyl), CO(C2-C6 alkenyl), CO(C2-C6 alkynyl), CO(C3-C8 cycloalkyl), CO(3 to 8-membered heterocyclyl), CO(aryl), or CO(heteroaryl) wherein each C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3 to 8-membered heterocyclyl, aryl, heteroaryl, CO(C1-C6 alkyl), CO(C2-C6 alkenyl), CO(C2-C6 alkynyl), CO(C3-C8 cycloalkyl), CO(3 to 8-membered heterocyclyl), CO(aryl), or CO(heteroaryl) is optionally substituted with one or more substituents selected from the group consisting of halogen, OH, NH2, CN, C1-C6 alkyl, aryl, heteroaryl and C1-C6 alkoxy
- provided that the prodrug is not:
2 more elements
A prodrug of a compound of Formula II:
- or a pharmaceutically acceptable salt, hydrate, solvate, or tautomer thereof, wherein:
- each R7, R8, R9, R10, R11, R12, R13, R14, R15 and R16 is independently H, OH or halogen provided that any two of R7, R8, R9, R10 and R11 and any two of R12, R13, R14, R15 and R16 are 2 adjacent OH groups and that (2) the prodrug is not:
Dependencies are inferred from the claim text.