Synthesis and inhibitory activity of 4-alkynyl and 4-alkenylquinazolines: Identification of new scaffolds for potent EGFR tyrosine kinase inhibitors

Synthesis and Photophysical Property Studies of the 2,6,8-Triaryl-4-(phenylethynyl)quinazolines

“…The reaction conditions were extended to other substrates using phenylacetylene, 2-ethynylpyridine and 3-butyn-2-ol to afford products 5b-h (Scheme 3). The analogous 2-substituted quinazolines bearing alkynyl substituent on the C-4 or C-6 position exhibit excellent EGFR or Aurora A kinase inhibition activity [23]. The presence of the two bromine atoms in compounds 5 makes them suitable candidates for further transformation through transition metal-catalyzed cross-coupling or metal exchange reactions to enable adequate diversity on the heterocycle.…”

“…Compounds 6a-l, on the other hand, can be used as substrates for the synthesis of metal complexes with iridium, palladium or platinum, for example, as a prelude to compounds with potential application as organic light-emitting diode in materials. Moreover, the analogous 2-substituted quinazolines bearing alkynyl substituent on the C-4 or C-6 position exhibit excellent EGFR or Aurora A kinase inhibition activity [23].…”

Synthesis of 4-Arylquinazolines by Arylation of Quinazolin-4-ones under Mild Conditions

“…4,5 Therefore, considerable progress in the synthesis of quinazoline derivatives have been achieved during the past decade. 6,7 Several protocols concerning C4-functionalization of quinazolines have been developed (Scheme 1): (1) Activation of the C-OH bond in the enolic tautomer by halogenation with reagents such as SOCl 2 , POCl 3 , and PCl 5 , and then nucleophilic substitution with nucleophiles to afford the corresponding 4-functionalized quinazolines C. 4a-j,5a,7b,i-m (2) Activation of the C-OH group with phosphonium salts (BOP, BrOP, PyBrOP, PyBOP, or PyAOP), and then nucleophilic substitution with nucleophiles or coupling with boronic acids to form 4-functionalized quinazolines C. 8,9 On the other hand, the in situ activation strategy has a long tradition, and many types of reactions have been developed so far, such as the combination of in situ activation and nucleophilic attack or cross-coupling reaction. Particularly, an array of tosylate cross-coupling via in situ activation has been well documented.…”

Cross-coupling of 4,5,6,7-tetrahydroindole with functionalized haloacetylenes on active surfaces of metal oxides and salts

“…A special attention among the compounds of the pyrrole and indole series is attracted by their ethynyl derivatives owing to the rich chemistry of the acetylene function [3][4][5][6][7]. In this connection considerable efforts are devoted to the development of new effective procedures for the synthesis of C-ethynylpyrroles and -indoles [8][9][10][11][12].…”