Bioactive Amino-Quinazolines: Synthesis and Therapeutic Applications

Abstract

The amino-quinazoline scaffold stands out as a privileged structure in Medicinal Chemistry, due to its pleiotropic pharmacological profile. It has been explored in the design and development of novel drug candidates for several therapeutic applications, including antihypertensive, antiinflammatory, antipsychotic, anti-Alzheimer, anticancer, antiviral, antibiotic, and antiparasitic treatments, among others. The therapeutic value of amino-quinazoline drugs was first demonstrated with the use of alpha 1-adrenoceptor antagonists, such as prazosin, doxazosin and terazosin. These drugs were initially approved for the treatment of hypertension and later for the treatment of benign prostatic hyperplasia. Several amino-quinazoline kinase inhibitors were introduced into the clinic as innovative therapeutic alternatives for cancer treatment after the U.S. Food and Drug Administration approved gefitinib in 2003 as a novel epidermal growth factor receptor inhibitor drug for non-small cell lung cancer. More recently, in 2021, the kinase inhibitor belumosudil was launched as a third-line therapy for adult and pediatric patients with chronic graft-versus-host disease. This article reviews the synthetic preparation methods and pharmacological activities of bioactive amino-quinazolines described in recent decades.