Discovery of Potent EGFR Inhibitors through the Incorporation of a 3D‐Aromatic‐Boron‐Rich‐Cluster into the 4‐Anilinoquinazoline Scaffold: Potential Drugs for Glioma Treatment. Issue 13 (22nd December 2017) - Couto, Marcos
Abstract: New 1, 7‐ closo ‐carboranylanilinoquinazoline hybrids have been identified as EGFR inhibitors, one of them with higher affinity than the parent compound erlotinib. The comparative docking analysis with compounds bearing bioisoster‐substructures, demonstrated the relevance of the 3D aromatic‐boron‐rich moiety for interacting into the EGFR ATP binding region. The capability to accumulate in glioma cells, the ability to cross the blood–brain barrier and the stability on simulated biological conditions, render these molecules as lead compounds for further structural modifications to obtain dual action drugs to treat glioblastoma. Abstract : Sir Lancelot : Erlotinib decorated with 3D boron‐rich clusters resulted in an anti‐EGFR lead molecule, derivative 1, with an IC50 value of 2.3 nm, ten‐fold higher than the parent compound. Hybrid 1 has great potential as a lead antitumor agent with dual action: targeting EGFR and for BNCT applications. The physicochemical properties also demonstrate that1 could be a template for further structural modifications to provide drug candidates for glioma treatment.