Computed Properties of C8H5ClN2O2. The protonation of heteroatoms in aromatic heterocycles can be divided into two categories: lone pairs of electrons are in the aromatic ring conjugated system; and lone pairs of electrons do not participate. Compound: 4-Chloroquinazoline-6,7-diol, is researched, Molecular C8H5ClN2O2, CAS is 1145671-36-8, about Development of a Potent Brain-Penetrant EGFR Tyrosine Kinase Inhibitor against Malignant Brain Tumors. Author is Tsang, Jonathan E.; Urner, Lorenz M.; Kim, Gyudong; Chow, Kingsley; Baufeld, Lynn; Faull, Kym; Cloughesy, Timothy F.; Clark, Peter M.; Jung, Michael E.; Nathanson, David A..
The epidermal growth factor receptor (EGFR) is genetically altered in nearly 60% of glioblastoma tumors; however, tyrosine kinase inhibitors (TKIs) against EGFR have failed to show efficacy for patients with these lethal brain tumors. This failure is attributed to the inability of clin. tested EGFR TKIs to cross the blood-brain barrier (BBB) and achieve adequate pharmacol. levels to inhibit various oncogenic forms of EGFR that drive glioblastoma. Through SAR anal., we developed compound 5 (JCN037)(I) from an anilinoquinazoline scaffold by ring fusion of the 6,7-dialkoxy groups to reduce the number of rotatable bonds and polar surface area and by introduction of an ortho-fluorine and meta-bromine on the aniline ring for improved potency and BBB penetration. Relative to the conventional EGFR TKIs erlotinib and lapatinib, JCN037 displayed potent activity against EGFR amplified/mutant patient-derived cell cultures, significant BBB penetration (2:1 brain-to-plasma ratio), and superior efficacy in an EGFR-driven orthotopic glioblastoma xenograft model.
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