Substituted Imidazo[1,2-c]Pyrimidines for Mutation-Resistant PRC2 Inhibition

The patent applies parameter changes by modifying the chemical structure of PRC2 inhibitors to create new compounds with improved properties. Specifically, the invention develops substituted imidazo[1,2-c]pyrimidines and related compounds that maintain PRC2 inhibition while achieving enhanced cellular potency, efficacy, stability, and safety profiles compared to existing inhibitors, thereby resolving the contradiction between reliability against mutations and adaptability across different parameters.

The patent applies local quality by designing compounds with specific substituted imidazo[1,2-c]pyrimidine structures that target the EED subunit with high specificity. The molecular structure incorporates particular substitution patterns and functional groups that enable selective binding to EED while maintaining manageable structural complexity, thus achieving broad therapeutic adaptability without excessive structural complexity.

The patent applies the intermediary principle by designing compounds that bind to the EED subunit as an intermediary target rather than directly inhibiting EZH2. This intermediary approach allows the compounds to effectively block PRC2 complex formation and function, achieving potent activity against cell lines with EZH2 activating mutations while maintaining reliable PRC2 inhibition, as EED is essential for PRC2 assembly and function regardless of EZH2 mutation status.