A Review on Current Synthetic Methods of 4-Aminoquinazoline Derivatives

Abstract

Quinazoline scaffold and its various derivatives, as an important category of heterocyclic compounds, have received much attention for the design and development of new drugs due to their various pharmacological properties like anticancer, anticonvulsant, antidepressant, antibacterial, antifungal, antioxidant, anti-HIV, antileishmanial, anticoccidial, antimalarial, anti-inflammatory, antileukemic, and antimutagenic. Among the various substituted quinazolines, 4-aminoquinazoline scaffold, as a privileged structure in medicinal chemistry, is present in many approved drugs and biologically active compounds. Furthermore, 4-aminoquinazoline derivatives are often applied as key intermediates in the preparation of bioactive compounds. The current review focuses on the key methods for the preparation of 4-aminoquinazoline derivatives, including the nucleophilic substitution reaction, metal-catalyzed approaches, microwave irradiation methods, cyclocondensation, and direct amination methods.

Discovery of ZJCK-6-46: A Potent, Selective, and Orally Available Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor for the Treatment of Alzheimer’s Disease

“…Yellow solid, yield 74%. 1 (R)-2-((6-(1H-Pyrrolo [2,3-b]pyridin-3-yl)quinazolin-4-yl)amino)-2-phenylethan-1-ol (25). Yellow solid, yield 54%.…”

“…Additionally, further structural modification at the 4-position of the quinazoline ring to further occupy the catalytic machinery in the pocket seems to have a significant impact on the activity and even selectivity for DYRK1A. Meanwhile, the 4-position of the quinazoline ring exhibiting high reactivity has been widely studied and reported. − Based on such a binding mode, with respect to synthetic tractability and freedom to operate, we have mainly focused our research on the catalytic machinery that has not been fully bound by the scaffold, resulting in the generation of 4-position substituted derivatives with completely different structures on the quinazoline moiety. Through fragment fusion and target-based drug design (TBDD) strategies, we reported the structure-guided development of the 6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)quinazoline-4-substituted series as DYRK1A inhibitors, which showed highly potent inhibitory activity against DYRK1A.…”

One-Pot Reactions of Triethyl Orthoformate with Amines

“…Conventional heating methods are generally applied, as well as other strategies that include the use of efficient and more environmentally friendly catalysts, or microwave irradiation. The synthesis of quinazoline derivatives has also attracted great attention in recent years, and numerous synthetic procedures for their formation have been developed [38][39][40][41][42][43]. It is currently in numerous accepted drugs and biologically active compounds, like erlotinib, gefitinib, prazosin, rutaecarpine and many others, as well as in clinical candidates and biologically active molecules [44][45][46].…”