BAF complex modulating compounds
Inventors
Anthony, Neville John • Vaswani, Rishi G. • Millan, David Simon • SCHILLER, Shawn E.R. • Wilson, Kevin J.
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-12685735-B2
Publication Date
2026-07-21
Expiration Date
Abstract
The present disclosure features compounds useful for the treatment of BAF complex-related disorders.
Core Innovation
The invention provides compounds having a specified chemical structure with constrained ring-formation parameters m and n, where m is 1, 2, 3, or 4 and n is 0, 1, 2, 3, or 4. The structure includes ring formation in which R1 combines with R2 and the atoms to which they are attached to form a 5- to 7-membered ring, or one R2 combines with another R2 and the atoms to which they are attached to form a 5- to 7-membered ring. Het is a 5- or 6-membered heterocycle, and the compounds include pharmaceutically acceptable salts.
The substituent groups R2, R3, R4, R5, R6, and R7 are constrained to defined sets of allowed functionalities. R2 is independently halo, hydroxy, thiol, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted amino; R3 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; R4 is hydrogen or optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C1-C6 alkyl C6-C10 aryl, or optionally substituted C1-C6 alkyl C2-C9 heteroaryl; R6 is hydrogen, halo, cyano, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 heteroalkyl, carboxyl, optionally substituted amide, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C6-C10 aryl; and R7 is cyano, halo, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl.
The disclosure also describes thiazole-containing benzamide analogs and related substituted compounds, including methyl 3-(2-(2-(3-(isopropylsulfonyl)benzamido)acetamido)thiazol-4-yl)benzoate and related analogs prepared and characterized by LCMS and 1H NMR. Additional examples include Compound 12 and structurally related analogs, with examples of substituted pyridyl, morpholine-bearing, hydroxymethyl/pyridyl, and other aryl or heteroaryl variations within the broader compound families described in the input items.
Claims Coverage
The consolidated claim coverage centers on one independent compound claim defining a broad structural genus with constrained ring formation, defined substituent sets for R2-R7, a restricted 5- or 6-membered Het, and pharmaceutically acceptable salts. The input items also repeatedly indicate a dependent claim family that narrows specific substituent choices and includes a BRG1/BRM level and/or activity reduction use in specified cancer cells.
Constrained core ring structure with m and n
A compound having the structure wherein m is 1, 2, 3, or 4 and n is 0, 1, 2, 3, or 4.
Ring formation from R1 and R2 or from R2 with another R2
R1 combines with R2 and the atoms to which they are attached to form a 5- to 7-membered ring, or one R2 combines with another R2 and the atoms to which they are attached to form a 5- to 7-membered ring.
Substituent restrictions for R2, R3, R4, and R5
R2 is independently halo, hydroxy, thiol, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, or optionally substituted amino; R3 and R5 are independently hydrogen or optionally substituted C1-C6 alkyl; and R4 is hydrogen, optionally substituted C1-C6 alkyl, optionally substituted C1-C6 heteroalkyl, optionally substituted C1-C6 alkyl C6-C10 aryl, or optionally substituted C1-C6 alkyl C2-C9 heteroaryl.
Het, R6, and R7 restrictions with salt option
Het is 5- or 6-membered heterocycle; R6 is hydrogen, halo, cyano, optionally substituted C1-C6 alkoxy, optionally substituted C1-C6 heteroalkyl, carboxyl, optionally substituted amide, optionally substituted C2-C9 heteroaryl, optionally substituted C2-C9 heterocyclyl, or optionally substituted C6-C10 aryl; R7 is cyano, halo, optionally substituted C1-C6 alkyl, or optionally substituted C1-C6 heteroalkyl; and the compound includes a pharmaceutically acceptable salt thereof.
BRG1/BRM activity reduction in specified cancer cells
A method that reduces the level and/or activity of BRG1 and/or BRM in specified cancer cells by contacting the cells with an effective amount of a compound of claim 1.
The claim coverage is dominated by a structurally defined compound class with ring-formation constraints, bounded substituent options for R2-R7, Het restricted to a 5- or 6-membered heterocycle, and inclusion of pharmaceutically acceptable salts. The consolidated family summary also includes a dependent use claim directed to reducing BRG1 and/or BRM level and/or activity in specified cancer cells by contacting the cells with an effective amount of the claimed compound.
Stated Advantages
Decreases BRG1 and/or BRM activity, including BRM-selective inhibition and BRM/BRG1 dual inhibition.
Reduces BRG1 and/or BRM level and/or activity in specified cancer-cell contexts.
Documented Applications
Therapeutic treatment of cancer, including melanoma, prostate cancer, breast cancer, bone cancer, renal cell carcinoma, hematologic cancer, and non-small cell lung cancer.
Therapeutic treatment of non-cancer disorders explicitly described as viral infections, including Retroviridae, HIV, HBV, and HCV.
Therapeutic treatment of genetic-disease contexts explicitly described, including Coffin Siris, neurofibromatosis, and CNS cancer.
BRG1/BRM-related evaluation in cancer cell contexts, including melanoma, prostate cancer, breast cancer, bone cancer, renal cell carcinoma, hematologic cancer cells, and uveal melanoma, with cellular growth inhibition profiles reported using GI50 and IP50 metrics.
ADP-Glo™ assay context for BRM/BRG1 ATPase inhibition evaluation.
Interested in licensing this patent?