Synthesis, structure, and in vitro anticancer activity of new polycyclic 1,2-diazines

Synthesis, anticancer and FGFR1 inhibitory activity of isoindolo[2,1-a][1,2,4]triazino[2,3-c]quinazoline derivatives

“…General synthetic protocol for 2R 1 6R 2 7R 3 8R 4 11R 5 12R 6 3hisoindolo [2,1a] [1,2,4] triazino [2,3c]quinazoline3,10(14bh)dione (2.1-2.33) To suspension of 5 mM of corresponding 3(2amino3R 2 4R 3 5R 4 phenyl)6R 1 1,2,4 triazin5(2h)ones (1.1-1.23) in 30 ml of glacial acetic acid 5 mM of 2formylbenzoic or opianic acid was added. Mixture was refluxed during 4 hours and cooled.…”

“…2methyl3hisoindolo [2,1a] [1,2,4]triazi no [2,3c]quinazoline3,10(14bH)dione 2.1 Yield 68.35 %; mp 239-240 °C 1 H NMR (400 MHz, dmso d6+ccl4) δ 8.32 (d,J=7.0 Hz,1H,8.17 (d,J=7.2 Hz,1H,8.12 (d,J=7.9 Hz,1H,7.93 (d,J=6.9 Hz,1H,3H,12,13), 7.46 (t, J=7.0 Hz, 1H, H-6), 6.94 (s, 1H, H14b), 2.30 (s, 3H, CH 3 ); 13 C NMR (126 MHz, DMSO) δ 165. 29, 162.49, 154.11, 151.96, 137.43, 135.91, 134.79, 134.76, 133.49, 131.91, 131.39, 129.18, 127.92, 126.21, 124.17, 121.31, 120.22, 72.67, 17.76; EIMS (m/z(I. rel.…”

“…%)) 316 (3.3), 276 (9.8), 275 (52.2), 274 (76.9), 247 (19.8), 177 (5), 151 (20.4) 3.84;N,17.73;O,10.12;Found: C,68.39;H,3.83;N,17.73;O,10.14. 2phenyl3hisoindolo[2,1a] [1,2,4] 2H,13),4H,H6,2Ph H3,4,5) 3.73;N,14.81;O,8.46;Found: C,73.05;H,3.76;N,14.85;O,8.49. 2(4ethylphenyl) ,4.46;N,13.78;O,7.87;Found: C,73.91;H,4.51;N,13.81;O,7.92.…”

“…For example, anticancer agents were identified among compounds containing condensed isoindole and benzodiazine fragments. The antitumor activity was revealed for isoindolo [2,1a]quinoxalin6(5H) ones (i) and benzo [5,6]isoindolo [1,2a]phthalazine 9,14diones (ii) [3,4], and moreover, wellknown antitumor agent luteolin A [5] contains fragment, which may be considered as azaanalog of isoindolo [1,2b]quinazoline system ( Figure 1). …”

“…Hence, considering promising antitumor activity of previously described compounds [6][7][8] we decided to combine [1,2,4]triazino [2,3c]quina zoline fragment and isoindole moiety in one mo lecule with the following study of anticancer and enzyme inhibitory activity of obtained compounds.…”