About 60% FDA approved drugs contain nitrogen heterocycles. Bifunctional linkers based on nitrogen heterocycles offer many advantages over classical polyethylene glycol (PEG) a and alkyl linkers:
Novelty: compounds with nitrogen heterocycles based linkers have unique structures comparing with compounds with widely used PEG or alkyl linkers
Structure Rigidity: ring structure with less rotatable bonds increases structure rigidity and improves compound drug likeness.
Aqueous Solubility: multiple nitrogen atoms in the linker and the formation of salts with acids offers options to improve compound aqueous solubility.
Chemical Diversity: diverse chemical structures of nitrogen heterocycles based linkers help medicinal chemistry optimization of compound properties.
Nitrogen heterocycles based linkers can be found in some of the most advanced PROTACs such as ARV-110 and ARV-471.