Design, Synthesis, and Biological Evaluation of Triazolyl- and Triazinyl-Quinazolinediones as Potential Antitumor Agents

Abstract

Novel 6(3-1H-1,2,4-triazol-1-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (7a–e) were synthesized from different enaminones (6a–e) with 6-hydrazinyl-3-phenylquinazoline-2,4(1H,3H)-dione. 2,6(4-2-Substituted-1,3,5-triazin-1(2H)-yl)-3-phenylquinazoline-2,4(1H,3H)-diones (8a–k) were synthesized from the reaction of 1-(2,4-dioxo-3-phenyl-1,2,3,4-tetrahydroquinazolin-6-yl)thiourea, urea, or guanidine (3a–c) with enaminones (6a–e), and a series from 3-substituted-2-imino-1,3,5-triazin-1(2H)-yl-sulfonyl-phenyl-1-methylquinazoline-2,4(1H,3H)-dione (12a–j) were obtained from the reaction of N-(diaminomethylene)-4-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl)benzenesulfonamide (11) with the enaminone (6a–j). The antitumor activity of the synthesized compounds was evaluated against two human cell lines: human colon carcinoma HCT116 and human hepatocellular carcinoma HEP-G2. Some of the tested compounds showed significant potency compared to the reference drug staurosporin.

Metal-Free N–H/C–H Carbonylation by Phenyl Isocyanate: Divergent Synthesis of Six-Membered N-Heterocycles

“…64 The title compound was synthesized according to the general procedure and obtained as a white solid (38 mg, 70%); 3:7 (EA/Hexane) as the eluent; 6-Bromo-3-phenylquinazoline-2,4(1H,3H)-dione (2t). 66 The title compound was synthesized according to the general procedure and obtained as a white solid (46 mg, 72%); 3:7 (EA/Hexane) as the eluent; 1 52 The title compound was synthesized according to the general procedure and obtained as a white solid (34 mg, 80%); 3:7 (EA/Hexane) as the eluent; 1 7-Fluoropyrrolo[1,2-a]quinoxalin-4(5H)-one (6d). 52 The title compound was synthesized according to the general procedure and obtained as a white solid (33 mg, 82%); 3:7 (EA/Hexane) as the eluent; 1 H-NMR (400 MHz, DMSO-d 6 ) δ 11.28 (s, 1H), 8.17 7-(Trifluoromethyl)pyrrolo[1,2-a]quinoxalin-4(5H)-one (6e).…”

Design and Synthesis of Novel Pyrazoles, Pyrazolines, and Pyridines From Chalcone Derivatives With the Assessment of Their in Vitro Anticancer Activity Against T-47d and Uacc-257 Cell Lines

“…Yellowish white solid from acetonitril, yield ( 0.9 g, 53%), mp: 278-280 0 C; IR (KBr, cm −1 ): 3410 (N-H), 3051 (=C-H), 2989 (-C-H); 1 H-NMR: δ 2.34 (s, 3H, p-CH3), 2.83 (s, 6H, N-(CH3)2), 3.04 (dd, J = 2.4 and 15.3 Hz, 1H, pyrazoline-H), 3.79 (q, 1H, pyrazoline-H), 5.80 (dd, 1H, pyrazoline-H), 6.62-7.77 (m, 8H, Ar-H), 7.93 (s, 2H, -NH2); MS (m/z, %):339 (M+1, 2), 338 (M+, 8), 222 (73), 205 (82), 147 (100), 146 (75), 132 (20), 118 (39), 91 (34), 77 (40)…”

Lewis Acid‐catalyzed Tandem Synthesis of Quinazoline‐2,4‐diones by Reaction of Isatins with Aryl/Alkyl Amines using TBHP as Oxidant

“…Quinazoline-2,4-dione motif is an important pharmacophore found in a wide range of bioactive molecules which include antihypertensive agents, [1] HIV-1 RNH inhibitors, [2] anticancer, [3] antitumor, [4] anti-inflammatory, [5] progesterone receptor antagonists [6] and antibacterial agents, [7] together with diabetic medicine and antiallergy. Some of the important bioactive molecules having quinazoline-2,4-diones framework are shown in Figure 1.…”