BAF Complex Modulating Compounds for BRG1 Disorder Treatment

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Solution Overview

Problem

Current treatments for disorders associated with alterations in BRG1 or BRM proteins, which are components of the BAF complex, are inadequate in modulating the complex's activity effectively.

Innovation Solution

Development of specific compounds, such as those represented by Formula I, which can modulate the activity of BAF complexes by interacting with BRG1 or BRM proteins, thereby treating associated disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments are used for disorders associated with BRG1 or BRM protein alterations, then treatment coverage is provided, but the effectiveness in modulating BAF complex activity is inadequate

Engineering Contradiction:
Improveeffectiveness in modulating BAF complex activityVSAvoidtreatment coverage for BAF complex disorders
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent employs parameter changes by developing compounds with specific molecular structures (Formula I) that alter the interaction parameters between inhibitors and BAF complex components. By modifying chemical parameters such as substituent groups (R1, R2, R3, R4, R5, R6), heteroatoms (X, Y, Z), and linkers (L), the invention achieves effective modulation of BAF complex activity where previous treatments failed.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If specific compounds (Formula I) are developed to modulate BAF complex activity, then therapeutic effectiveness is improved, but the complexity of the treatment regimen increases

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidtreatment regimen complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the complex molecular structure of Formula I into distinct functional segments: heteroaryl/heterocyclyl groups (R1-R6), core structure (X, Y, Z), linker (L), and substituent (B). This segmentation allows for systematic optimization of each component's contribution to BAF complex modulation while maintaining overall therapeutic effectiveness.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses parameter changes to manage complexity by establishing defined ranges and options for each molecular parameter (R1-C6-C10 aryl, R2-C2-C9 heteroaryl, X/Y/Z as N or CH, L as alkylene or heteroalkylene). These parameter specifications provide a structured framework that guides compound selection and treatment personalization without creating unmanageable complexity.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3917527B1Compounds and uses thereof
Publication Date: 2025.04.23 FOGHORN THERAPEUTICS INC
  • EP3917527B1 patent drawingFigure 1
  • EP3917527B1 patent drawingFigure 2A
  • EP3917527B1 patent drawingFigure 2B

AI summary

The present disclosure features compounds useful for the treatment of BAF complex-related disorders.