4797-80-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of 3-hydroxyquinazoline-2,4(1H,3H)-diones as dual inhibitors of HIV-1 reverse transcriptase-associated RNase H and integrase
Gao, Ping,Cheng, Xiqiang,Sun, Lin,Song, Shu,álvarez, Mar,Luczkowiak, Joanna,Pannecouque, Christophe,De Clercq, Erik,Menéndez-Arias, Luis,Zhan, Peng,Liu, Xinyong
, p. 3836 - 3845 (2019)
A novel series of 3-hydroxyquinazoline-2,4(1H,3H)-diones derivatives has been designed and synthesized. Their biochemical characterization revealed that most of the compounds were effective inhibitors of HIV-1 RNase H activity at sub to low micromolar concentrations. Among them, II-4 was the most potent in enzymatic assays, showing an IC50 value of 0.41 ± 0.13 μM, almost five times lower than the IC50 obtained with β-thujaplicinol. In addition, II-4 was also effective in inhibiting HIV-1 IN strand transfer activity (IC50 = 0.85 ± 0.18 μM) but less potent than raltegravir (IC50 = 71 ± 14 nM). Despite its relatively low cytotoxicity, the efficiency of II-4 in cell culture was limited by its poor membrane permeability. Nevertheless, structure-activity relationships and molecular modeling studies confirmed the importance of tested 3-hydroxyquinazoline-2,4(1H,3H)-diones as useful leads for further optimization.
3-hydroxy quinazoline-2,4(1H,3H)-diketone derivative as well as preparation method and application thereof
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Paragraph 0042-0044; 0079; 0080, (2019/10/01)
The invention provides a 3-hydroxy quinazoline-2,4(1H,3H)-diketone derivative which is of a structure of a formula I or II shown in the specification. The invention furthermore relates to a preparation method of the derivative and application of the derivative as an HIV (human immunodeficiency virus) inhibitor in preparing anti-AIDS (acquired immune deficiency syndrome) medicines.
3-Hydroxy-1H-quinazoline-2,4-dione as a New Scaffold to Develop Potent and Selective Inhibitors of the Tumor-Associated Carbonic Anhydrases IX and XII
Falsini, Matteo,Squarcialupi, Lucia,Catarzi, Daniela,Varano, Flavia,Betti, Marco,Di Cesare Mannelli, Lorenzo,Tenci, Barbara,Ghelardini, Carla,Tanc, Muhammet,Angeli, Andrea,Supuran, Claudiu T.,Colotta, Vittoria
, p. 6428 - 6439 (2017/08/02)
In this paper, we describe the discovery of the 3-hydroxyquinazoline-2,4-dione as a useful scaffold to obtain potent inhibitors of the tumor-associated human carbonic anhydrases (hCAs) IX and XII. A set of derivatives (1-29), bearing different substituents on the fused benzo ring (Cl, NO2, NH2, CF3, ureido, amido, heterocycles), were synthesized, and several of them showed nanomolar activity in inhibiting the hCA IX and XII isoforms, while they were ineffective against the cytosolic enzymes hCAs I and II. Some selected compounds were tested for their antiproliferative activity against HT-29 colon cancer cell lines. After 48 h of treatment with the lower dose (30 μM), derivatives 12, 14, 15, and 19 were significantly active, inducing a mortality by about 50% in both normoxia and hypoxia. This finding led us to hypothesize for these compounds more than one mechanism of action involving both CAs IX and XII and other not yet identified target(s).
Methods for synthesizing libraries of dihydro-quinazolinones
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, (2008/06/13)
Synthetic methods for solution and solid-phase synthesis of combinatorial libraries of dihydro-quinazolinones, including synthesis of 2,3-dihydro-3-alkoxy-4(1H)-quinazolinones or 2,3-dihydro-3-hydroxy-4(1H)-quinazolinones via the Lewis-acid catalyzed reaction of an appropriate 2-aminobenzamide with an aldehyde at ambient temperature performed on a solid support or in solution.
