Hydroxypyrrolidine Bifunctional Compound for Target Protein Degradation

The patent modifies the chemical structure parameters of the bifunctional compound by changing the core scaffold from proline or cyclopropane to hydroxypyrrolidine, and by optimizing the linker length and composition. These parameter changes enable the compound to bind to a broader range of target proteins while maintaining effective degradation induction, thus expanding the range of applicable target proteins without sacrificing degradation effectiveness.

The patent employs local quality by designing the hydroxypyrrolidine core with specific functional groups at different positions that can selectively interact with various target proteins. The compound maintains localized high-affinity binding regions while having overall versatility, allowing it to effectively degrade multiple target proteins without diluting its degradation effectiveness. The specific substitution patterns on the hydroxypyrrolidine ring create distinct binding pockets for different targets.

The patent creates a composite bifunctional molecule combining a VHL-binding ligand (e.g., chalcone derivative) with a target protein ligand through a carefully designed linker. This composite structure maintains the low molecular weight advantage for easy administration and metabolism while achieving effective target protein degradation through the synergistic action of both functional moieties. The hydroxypyrrolidine core acts as an efficient scaffold that coordinates both binding functions within a compact molecular framework.