EZH2 Modulator Compounds With Longer Residence Time and Permeability
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Solution Overview
Problem
Current treatments for conditions associated with methyl modifying enzymes, particularly EZH2, are limited in efficacy and duration, and there is a need for compounds that can effectively modulate the activity of these enzymes to treat various diseases, including cancer.
Innovation Solution
Development of compounds, such as those represented by structural Formula I, which enhance residence time and permeability, allowing for improved cellular potency in modulating the activity of EZH2 and other methyl modifying enzymes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for conditions associated with methyl modifying enzymes are used, then they can address basic treatment needs, but they lack compounds with enhanced residence time and permeability, resulting in reduced cellular potency
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structure parameters of EZH2 inhibitor compounds. Specifically, the patent optimizes molecular weight, lipophilicity (clogP), hydrogen bond donors/acceptors, and other physicochemical parameters to achieve compounds with both enhanced cellular potency and prolonged residence time. The structural formulas I-VI and their variants represent systematic parameter optimization to resolve the contradiction between potency and duration of action
2Reliability
If current treatments for conditions associated with methyl modifying enzymes are used, then they can provide basic therapeutic effect, but they lack enhanced permeability, limiting their effectiveness
Solution Approach 1:
The patent optimizes permeability parameters including membrane permeability, blood-brain barrier penetration, and cellular uptake efficiency. The structural modifications in formulas I-VI specifically address permeability by adjusting molecular size, lipophilicity, and hydrophobicity to enhance drug delivery to target tissues while maintaining therapeutic effectiveness
Data Source
AI summary
Provided are novel compounds of Formula (I):and pharmaceutically acceptable salts thereof, which are useful for treating a variety of diseases, disorders or conditions, associated with methyl modifying enzymes. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I), pharmaceutically acceptable salts thereof, and methods for their use in treating one or more diseases, disorders or conditions, associated with methyl modifying enzymes.