Compounds and uses thereof
Inventors
Anthony, Neville John • Millan, David Simon • Vaswani, Rishi G. • Schiller, Shawn E. R.
Assignees
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Publication Number
US-11497752-B2
Publication Date
2022-11-15
Expiration Date
Abstract
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
Core Innovation
The disclosed subject matter relates to structurally defined compounds presented under Formula I and related structure sets, including pharmaceutically acceptable salts and pharmaceutical composition embodiments using pharmaceutically acceptable excipients. The compounds are described with variable substituent frameworks across heteroaryl, heterocyclyl, alkyl, cycloalkyl, aryl, and heteroaryl positions, and the patent also references specific numbered compounds and tables of representative structures.
The core chemistry is directed to BAF-complex modulatory compounds that inhibit BRM and/or BRG1, including BRM/BRG1 dual inhibition and BRM-selective inhibition, and to treating BAF complex-related disorders. The disclosed therapeutic concept emphasizes cancer, including BRG1 loss-of-function contexts and drug-resistant or therapy-failed cancers, and also describes inducing apoptosis and reducing or targeting metastatic progression.
The document further describes thiazole-containing amide, benzamide, and related compounds, including chiral amino-thiazole building blocks, intermediates, and named examples with analytical characterization. Additional formula families are described as Formula IV, Formula IVa, Formula V, and related sub-formulas, with defined substituent ranges and illustrative compound sets, while the partial content also references specific numbered compounds and table-based structural embodiments.
Claims Coverage
The consolidated claim coverage spans multiple independent structural claim families. Across the provided items, the main inventive features are broad Formula I compound definitions with variable substituents and pharmaceutically acceptable salts, separate coverage of compounds corresponding to any one of specified structures or table-defined compounds, and related pharmaceutical composition claims with a pharmaceutically acceptable excipient.
Formula I compound structure with variable substituents
A compound having the structure of Formula I, wherein B is optionally substituted C2-C9 heteroaryl or C2-C9 heterocyclyl; R1 is optionally substituted C1-C3 alkyl or optionally substituted C3-C6 cycloalkyl; each of R3 and R5 is independently selected from H, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl; R4 is hydrogen or optionally substituted C1-C6 heteroalkyl; and R6 is optionally substituted C6-C10 aryl or optionally substituted C2-C9 heteroaryl, together with pharmaceutically acceptable salts thereof.
Compound defined by any one of specified structures
A compound having the structure of any one of specified compounds, including claims that reference a listed set or table-defined set of compounds, together with pharmaceutically acceptable salts thereof.
Pharmaceutical composition comprising the claimed compound and excipient
A pharmaceutical composition that includes the claimed compound together with a pharmaceutically acceptable excipient.
Formula IV and Formula IVa compound scaffold
A compound defined by Formula IV and related Formula IVa, with substituent variables R10, R11, R9, and R12 and pharmaceutically acceptable salts.
Formula V and related sub-formulas compound scaffold
A compound defined by Formula V and related sub-formulas, with substituent variables including R14, R15, R13, R16, ra, rb, rc, rd, r, and s, together with pharmaceutically acceptable salts.
Table-defined compound set 106-241
A compound having the structure of any one of compounds 106-241 as set out in Table 4, together with pharmaceutically acceptable salts thereof.
Overall, the claim coverage centers on structurally defined compound families, especially Formula I compounds with multiple substituent-variable constraints and separate coverage of specified compound sets or table-defined compounds, all including pharmaceutically acceptable salts. Dependent narrowing appears for selected Formula I substituents, and pharmaceutical composition embodiments add a pharmaceutically acceptable excipient.
Stated Advantages
Inducing apoptosis.
Reducing or targeting metastatic progression.
BRM/BRG1 selectivity is characterized by reported differences of less than or equal to 10-fold.
The disclosed compounds are described in therapy-relevant contexts including drug-resistant or therapy-failed cancers.
Documented Applications
Treating BAF complex-related disorders, primarily cancer.
Treating BRG1 loss-of-function disorders.
Treating drug-resistant or therapy-failed cancers.
Cancer types explicitly referenced include non-small cell lung cancer, colorectal cancer, melanoma, prostate cancer, breast cancer, renal cell carcinoma, and hematologic cancers.
Inducing apoptosis.
Reducing or targeting metastatic progression.
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