Synthesis and Biological Evaluation of New Quinazoline and Cinnoline Derivatives as Potential Atypical Antipsychotics

Abstract

Four new diaza analogues (14, 15, 23, and 24) of the conformationally constrained aminobutyrophenone derivatives QF0104B (5) and QF0108B (6) were synthesized (Schemes 2 and 3), and evaluated for their binding affinities (Table) towards the serotonin 5-HT2A and 5-HT2C, and the dopamine D2 receptors. Among the new compounds, the quinazoline derivative 15 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydroquinazolin-5-one) exhibited the highest affinities towards the serotonin 5-HT2A and dopamine D2 receptors, and it is in the borderline of potential atypical antipsychotics. The cinnoline derivative 23 (= 7-{[4-(4-fluorobenzoyl)piperidin-1-yl]methyl}-5,6,7,8-tetrahydro-3-methylcinnolin-5-one) displayed high selectivity in its binding profile towards the 5-HT2C compared to both the 5-HT2A and D2 receptors.

Design, Synthesis and Molecular Properties Prediction of Novel Quinazoline Derivatives as Potent Antibacterial Agents

“…Tetrahydrofuran was distilled from sodium benzophenone ketyl and degassed thoroughly with dry argon directly before use. Unless otherwise noted, organic extracts were dried with anhydrous Na2SO4, filtered through a fitted glass funnel and concentrated with a rotary evaporator (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30). Flash chromatography was performed with silica gel (200-300 mesh) by using the mobile phase indicated.…”

“…Researchers have already determined many therapeutic activities of quinazoline derivatives, including anticancer [3][4][5][6], antiinflammation [7,8], antibacterial [9][10][11][12], antivirus [13], anticytotoxin [14], antispasm [15], antituberculosis [16], antioxident [17], antimalarial [18], antihypertension [19], antiobesity [20], antipsychotic [21] and antidiabetes [22], etc.…”

Utility of 4-Aryl-8-arylidene-3, 4, 5, 6, 7, 8-hexa-hydroquinazoline-2-thiol for the Synthesis of Some New Heterocycles as Antioxidant Agents

“…Quinazoline derivatives, which belong to the N-containing heterocyclic compounds, have caused universal concerns due to their biopharmaceutical activities. Researchers have already determined many therapeutic activities of quinazoline derivatives, including anticancer [1][2][3][4] , antiinflammatory 5,6 , antibacterial [7][8][9][10] , analgesic 5,9 , antiviral 11 , anticytotoxic 12 , antispasm 9,13 , antituberculosis 14 , antioxidant 15 , antimalarial 16 , antihypertension 17 , antiobesity 18 , antipsychotic 19 , anti-diabetics 20 , etc. Medicinal chemists synthesized quinazoline derivatives with different biological activities by installing various active groups to the quinazoline moiety.…”

(8-Chloro-3-methyl-1H-pyrazolo[4,3-c]cinnolin-1-yl) (pyridin-4-yl)methanone

“…Literature shows several compounds containing a cinnoline moiety with a wide spectrum of pharmacological activities, like antimicrobial, anti-inflammatory, anticancer, antimalarial and antipsychotic etc. [1][2][3][4][5]. As a part of research on benzfused heterocyclic compounds [6], we report here the synthesis of (8-chloro-3-methyl-1H-pyrazolo [4,3-c]cinnolin-1-yl) (pyridin-4-yl)methanone 2.…”