Pyrazoloquinazolines: Synthetic strategies and bioactivities

Design and Synthesis of Non-Covalent Imidazo[1,2-a]quinoxaline-Based Inhibitors of EGFR and Their Anti-Cancer Assessment

“…Therefore, the development of novel non-covalent and reversible EGFR inhibitors with alternate scaffolds which do not involve covalent reaction with Cys797 is warranted [9][10][11]. In the recent past, we were interested in developing the synthetic approaches and assessing the biological activities of pyrazolo[1,5-c]quinazolines [12][13][14][15], which eventually emerged as active EGFR inhibitors [16,17]. It was observed that polar substitutions (-CO2Me, -COAr, -CN and -NH2) on pyrazole (e.g., I and II of our previous studies) were critical for binding with EGFR residual amino acids [16,17].…”

“…Furthermore, imidazole-fused [11,18] quinoxaline [19], in particular, imidazo[1,2-a]quinoxalines have gained significant interest due to their broad-spectrum activities [20,21], including IκB kinase (IKK) [22] and lymphocyte-specific protein tyrosine kinase (LCK) [23] inhibitory activities. In the recent past, we were interested in developing the synthetic approaches and assessing the biological activities of pyrazolo[1,5-c]quinazolines [12][13][14][15], which eventually emerged as active EGFR inhibitors [16,17]. It was observed that polar substitutions (-CO 2 Me, -COAr, -CN and -NH 2 ) on pyrazole (e.g., I and II of our previous studies) were critical for binding with EGFR residual amino acids [16,17].…”

A Protocol for the Synthesis of CF2H-Containing Pyrazolo[1,5-c]quinazolines from 3-Ylideneoxindoles and in Situ Generated CF2HCHN2

“…Pyrazolo­[1,5- c ]­quinazolines, a class of N -fused heterocycles bearing pyrazole and quinazoline moieties, have attracted tremendous interest among researchers due to the important bioactivities associated with these compounds (Figure ), such as AMPA receptors, Gly/NMDA antagonist, benzodiazepine/adenosine receptor, and phosphodiesterase 10 A inhibitors . Accordingly, substantial effort has been devoted to the development of synthetic methods for the pyrazolo­[1,5- c ]­quinazoline derivatives. , However, most of them are mainly limited to the use of complex starting materials, multistep reaction strategy, harsh reaction conditions or tedious isolation procedure. From the standpoint of atom- and step-economy, the development of facile and practical methods with easily accessible precursors for the construction of pyrazolo­[1,5- c ]­quinazolines is still desirable.…”

An Efficient Protocol for the Synthesis of Pyrazolo[1,5-c]quinazolines by a Staudinger–Aza-Wittig–Dehydroaromatization Sequence

“…Pyrazoloquinazolines are an important class of N-heterocycles that can be categorized into eleven groups. 1 Because of their wide range of bioactivities, 2 various methods have been developed to construct these compounds. 1,3 It has been reported that the class of pyrazolo [1,5-c]quinazolines can be used as potent IKK inhibitors, 4 AMPA and kainate receptors, 5 Gly/NMDA receptor antagonists, 6 benzodiazepine receptor ligands, 7 phosphodiesterase 10A inhibitors, 8 epidermal growth factor receptor (EGFR) inhibitors, 9 and adenosine receptor antagonists.…”

“…1 Because of their wide range of bioactivities, 2 various methods have been developed to construct these compounds. 1,3 It has been reported that the class of pyrazolo [1,5-c]quinazolines can be used as potent IKK inhibitors, 4 AMPA and kainate receptors, 5 Gly/NMDA receptor antagonists, 6 benzodiazepine receptor ligands, 7 phosphodiesterase 10A inhibitors, 8 epidermal growth factor receptor (EGFR) inhibitors, 9 and adenosine receptor antagonists. 10 The potential biological activities of pyrazolo [1,5-c]quinazoline compounds have greatly expanded research into these compounds.…”