SYNTHESIS OF MULTI-RING PYRROLO[3,2-D]PYRIMIDINE DERIVATIVES AND INVESTIGATION OF THEIR BIOLOGICAL ACTIVITY

The pyrrolo[3,2-d]pyrimidine (9-deazapurine) scaffold is a privileged core in medicinal chemistry, functioning as a key bioisostere for natural purine bases. Its structural geometry allows it to mimic the hydrogen-bonding patterns of ATP, making it a powerful "hinge-binding" motif for kinase inhibition. While simple bicyclic derivatives are well-known, expanding this core into rigid, multi-ring (polycyclic) architectures offers superior potential. These polycyclic systems are designed to occupy deeper hydrophobic pockets within the kinase domain, enhancing both binding affinity and isoform selectivity while simultaneously improving metabolic stability through reduced conformational flexibility.