Quinazolines belong to heterocyclic chemistry, also known as 1,3-naphthalenes. The backbone consists of two six-membered aromatic rings fused to each other, with two nitrogen atoms at positions 1 and 3 on the backbone. The presence of these two nitrogen atoms in quinazoline increases its importance in pharmaceutical and biological reactions. Quinazolines and their derivatives are among the most important heterocyclic compounds due to their diverse chemical reactivity and important range of biological activities.
The Journal of Medicinal Chemistry releases an article titled "Identification of the Clinical Candidate PF-07284890 (ARRY-461), a Highly Potent and Brain Penetrant BRAF Inhibitor for the Treatment of Cancer". Mutations in the BRAF gene result in MAPK pathway activation that are most commonly found in human melanomas. The BRAF V600E mutation is among the most frequent types. Present BRAF inhibitors have significantly improved treatment outcomes for patients with BRAF V600-mutant cancers. However, their effectiveness is limited by disease progression in the brain as they don’t adequately penetrate the blood-brain barrier (BBB).
Pfizer’s Tinlorafenib (formerly PF 07284890) is a highly brain-penetrant inhibitor of BRAF V600-mutant tumors, and currently in a phase 1 clinical trial (NCT04543188).