Simple and Efficient Synthesis of Novel 3‐Substituted 2‐Thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones and Their Reactions with Alkyl Halides and α‐Glycopyranosyl Bromides

Abstract

A series of 3‐substituted 2‐thioxo‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 4a–e were synthesized from the reaction of 3‐aminonaphthalene‐2‐carboxylic acid 1 with isothiocyanate derivatives 2a–e. The alkylation of 4a–e with alkyl halides gave 3‐substituted 2‐alkylsulfanyl‐2,3‐dihydro‐1H‐benzo[g]quinazolin‐4‐ones 5a–o. S‐Glycosylation was carried out via the reaction of 4a–e with glycopyranosyl bromides 7a and 7b under anhydrous alkaline conditions. The structure of the compounds was established as S‐nucleoside and not N‐nucleoside. Conformational analysis has been studied by homonuclear and heteronuclear two‐dimensional NMR methods (2D DFQ‐COSY, heteronuclear multiple quantum coherence, and heteronuclear multiple bond correlation). The S site of alkylation and glycosylation was determined from the 1H and 13C heteronuclear multiple quantum coherence experiments.

Antiproliferative and Antiangiogenic Properties of New VEGFR-2-targeting 2-thioxobenzo[g]quinazoline Derivatives (In Vitro)

“…The benzoquinazoline core was confirmed by observation of the three aromatic resonance pairs in the range of 8.8–7.5 ppm. The first is two singlets for H-5 and H-10; the second is for H-6 and H-9 in the form of two broad doublets, and the third is two identical broad triplets at around 7.60 and 7.50 ppm for H-7 and H-8, respectively [ 13 , 17 , 23 , 24 ]. The core structure was confirmed from the 12 typical 13 C-resonances, including the most downfield ones at around 161.0 and 156.0 ppm, assignable for C-4 and C-2, respectively.…”

“…White amorphous powder (82%); mp 296 °C; 1 H NMR (700 MHz, DMSO- d 6 ): δ 12.96 (s, 1H, -NH-), 8.69 (s, 1H, H-5), 8.12 (br d, J = 8 Hz, 1H, H-6), 7.93 (br d, J = 8 Hz, 1H, H-9), 7.74 (s, 1H, H-10), 7.62 (br t, J = 7.4 Hz, 1H, H-7), 7.50 (br t, J = 7.4 Hz, 1H, H-8), 4.49 (t, q = 7 Hz, 2H, H-1′), 1.27 (t, J = 7 Hz, 3H, H-2′); 13 C NMR (175 MHz, DMSO- d 6 ): δ 175.4 (C-2), 159.5 (C-4), 136.6 (C-4b,9a), 135.3 (C-5a), 130.0 (C-5), 129.9 (C-6), 129.7 (C-8), 127.7 (C-4a), 126.1 (C-9), 116.0 (C-7), 111.5 (C-10), 41.4 (C-1′), 12.7 (C-2′); HRMS-MS: m / z calcd. for C 14 H 12 N 2 OS (M) •+ 256.0670, found 256.0693 [ 23 , 24 ].…”

“…White amorphous powder (73%); mp 107–109 °C; 1 H NMR (500 MHz, DMSO- d6 ): δ 8.79 (s, 1H, H-5), 8.18 (br d, J = 8.3 Hz, 1H, H-6), 8.10 (s, 1H, H-10), 8.08 (br d, J = 8.3 Hz, 1H, H-9), 7.65 (br t, J = 7.8 Hz, 1H, H-7), 7.55 (br t, J = 7.8 Hz, 1H, H-8), 4.10 (q, J = 7.1 Hz, 2H, H-1″), 3.31 (q, J = 7.3 Hz, 2H, H-1′), 1.43 (t, J = 7.3 Hz, 3H, H-2′), 1.31 (t, J = 7.1 Hz, 3H, H-2″); 13 C NMR (125 MHz, DMSO- d6 ): δ 161.1 (C-4), 155.7 (C-2), 142.8 (C-4b), 136.8 (C-5a), 130.9 (C-9a), 129.7 (C-5), 129.0 (C-6), 128.3 (C-8), 128.1 (C-4a), 126.4 (C-9), 123.2 (C-7), 118.9 (C-10), 40.5 (C-1″ hidden by DMSOd6 signal), 26.4 (C-1′), 14.5 (C-2′), 13.7 (C-2″); HRMS-MS: m / z calcd. for C 16 H 16 N 2 OS (M) •+ 284.0983, found 284.1003 [ 24 ].…”

Investigation of some benzoquinazoline and quinazoline derivatives as novel inhibitors of HCV-NS3/4A protease: biological, molecular docking and QSAR studies

“…All compounds were previously synthesized and fully characterized. 17,19,21,23 The general procedures for preparation of compounds 7, 8, 14 and 15 were reported, 17,19 however, their characterization data are reported herein for the rst time as following: 3-Methyl-2-hydrazinylbenzo[g]quinazolin-4(3H)-one (7). Yield 70%; mp 284-286 C; 1 H NMR (700 MHz, DMSO- 3-Methyl-2-hydrazinyl-6-methyl-3H-quinazolin-4-one (14).…”

Anticancer Activity of S-Glycosylated Quinazoline Derivatives

“…Recently, several S-glycosides, a new non-classical class of nucleosides, have been proved to be potential anticancer agents against many cell Lines Our research interest focused on the design and synthesis of new small heterocyclic nucleosides targeting cancer especially MCF-7 and HepG2 cell lines. The elaboration of quinazoline derivatives linked with glycopyranose sugars (Figure 1) to form the target nucleosides was our task [61,64]. The in vitro cytotoxic activity against MCF-7 and HepG2 cell lines showed effective anti-proliferative activity of the analyzed derivatives with lower IC 50 values especially 2a with IC 50 =2.09 and 2.08 µM against MCF-7 and HepG2, respectively, and their treatments were safe against the normal cell line Gingival mesenchymal stem cells (GMSC).…”