CD73 inhibitors
Inventors
Du, Xiaohui • Eksterowicz, John • Fantin, Valeria R. • Jackson, Erica L. • Sun, Daqing • YE, Qiuping • Moore, Jared
Assignees
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Publication Number
US-11576922-B2
Publication Date
2023-02-14
Expiration Date
Abstract
Described herein are CD73 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of cancer, infections, and neurodegenerative diseases.
Core Innovation
The disclosure describes compounds of Formula (IV), or pharmaceutically acceptable salts, solvates, or stereoisomers thereof, with A being —O— or —CH2— and with extensive substituent variability governed by groups R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, Y3, Y4, R13, R14, R15, R16, R17, R18, and R30, R33, and R34. Variable substituents are defined with allowed chemical classes and optional substitution counts, and the scope includes ester-like and glycerol ester derivative patterns involving R40 and R41.
The invention further constrains the structural variability through defined chemical relationships among substituents, including that R1 and R2 can be taken together with the nitrogen atom to which they are attached to form a heterocycloalkyl. It also defines Y3 as —CR13R14— and Y4 as —O—, specifies that R13 and R14 are hydrogen, and states that R16 and R17 can be taken together to form a heterocycloalkyl.
The document also describes chlorinated heteroaryl phosphonic acid derivatives, including substituted pyrazolo[3,4-d]pyrimidine–tetrahydrofuran derivatives and chlorinated triazolo[4,5-d]pyrimidine phosphonic acid derivatives. The examples include phosphonate and phosphonic acid intermediates and final deprotected products, together with stereodefined substituent patterns, amino substituent variation, and MS (ESI) characterization.
Claims Coverage
Three independent claim themes are reflected across the inputs: Formula (IV) compounds with extensive substituent-defined structural variability, a Markush-style selection limited by A being —O— or —CH2—, and a cancer treatment method using a Formula (IV) compound. The shared inventive features center on the Formula (IV) scaffold, optional pharmaceutically acceptable forms, and specific substituent constraints.
Formula (IV) compound with defined substituent variability
A compound of Formula (IV), or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof, wherein A is —O— or —CH2—, and the compound is defined by specified substituent classes and constraints for R1, R2, R3, R4, R5, R6, R7, R8, R9, R10, Y3, Y4, R13, R14, R15, R16, R17, and R18, including optional substitution counts and rules for taking R1 and R2, R16 and R17, and R34 and R33 together with nitrogen atoms or attached atoms to form heterocycloalkyl structures.
R30/R33/R34 non-hydrogen and ester-like linker constraints
The compound further includes structural variables R30, R33, and R34 with a constraint that at least one of R30, R33, or R34 is not hydrogen; R34 and R33 can be taken together with the atoms to which they are attached to form a heterocycloalkyl, and R40 together with R41 is defined including R41 as a glycerol ester derivative, with ester-like and alkylene linker patterns and v being 1, 2, 3, or 4.
Markush selection with A limited to oxygen or methylene
A compound or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof selected from a Markush-style list, wherein A is —O— or —CH2—.
Cancer treatment using Formula (IV) compound
A method for treating cancer by administering a compound of Formula (IV), or a pharmaceutically acceptable salt, solvate, or stereoisomer of the compound, to a subject.
The claims are centered on Formula (IV) compounds with extensive variable substituent families and specific structural relationships, plus a Markush-selected subset limited by A being —O— or —CH2—. One claim theme also expressly recites cancer treatment by administration of a Formula (IV) compound.
Stated Advantages
Not explicitly described in patent.
Documented Applications
A method for treating cancer by administering a compound of Formula (IV), or a pharmaceutically acceptable salt, solvate, or stereoisomer of the compound, to a subject.
Combination therapy for cancer using the disclosed compound together with a second therapeutic agent and/or co-therapies including hormone blocking therapies, passive immunotherapy, additional anti-cancer drug classes, supportive care agents, and radiation therapy [procedural detail omitted for safety].
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