4797-75-5Relevant academic research and scientific papers
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).
One-pot synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and palladium-catalyzed oxidative isocyanide-insertion
Ji, Fei,Lv, Mei-Fang,Yi, Wen-Bin,Cai, Chun
, p. 5766 - 5772 (2014/07/22)
An efficient and practical two-step process has been developed for the synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and palladium-catalyzed oxidative isocyanide-insertion in one pot. This regioselective procedure could construct a wide range of 2-amino-4(3H)- quinazolinones in moderate to excellent yields. Furthermore, the methodology also had distinct advantages of easily accessible starting materials and operational simplicity. the Partner Organisations 2014.
Discovery of N-Arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide Derivatives as HCV NS5B Polymerase Inhibitors
Deore, Ravindra Ramesh,Chen, Grace Shiahuy,Chang, Pei-Teh,Chern, Ting-Rong,Lai, Shin-Yu,Chuang, Ming-Hsieh,Lin, Jung-Hsin,Kung, Fan-Lu,Chen, Chien-Shu,Chiou, Chun-Tang,Chern, Ji-Wang
experimental part, p. 850 - 860 (2012/07/14)
The metal ion chelating β-N-hydroxy-γ-ketocarboxamide pharmacophore was integrated into a quinazolinone scaffold, leading to N-arylalkyl-3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide derivatives as hepatitisC virus (HCV) NS5B polymerase inhibitors. Lead optimization led to the identification of N-phenylpropyl carboxamide 9k (IC50=8.8μM). Compound 9k possesses selectivity toward HCV1b replicon Ava.5 cells (EC50=17.5μM) over parent Huh-7 cells (CC50=187.5μM). Compound 9k effects a mixed mode of NS5B inhibition, with NTP-competitive displacement properties. The interaction between 9k and NS5B is stabilized by the presence of magnesium ions. Docking studies showed that the binding orientation of 9k occupies the central portions of both magnesium-mediated and NTP-ribose-response binding sites within the active site region of NS5B. As a result, 3-hydroxy-4-oxo-3,4-dihydroquinazolin-2-carboxamide derivatives are disclosed herein as novel, mainly active site inhibitors of HCV NS5B polymerase.
Synthesis and application of N-hydroxylamine derivatives as potential replacements for HOBt
El-Faham, Ayman,Albericio, Fernando
supporting information; experimental part, p. 1499 - 1501 (2009/07/11)
Several heterocycles containing N-hydroxylamine were prepared and tested as coupling additives to replace the use of N-hydroxybenzolriazole (HOBt.) derivatives. On the basis of our results on coupling yield and racemization-suppressing properties, we propose N-hydroxyindolin-2-one and 6- cfiloro-N-hydroxy-2-phenylbenzimidazole as suitable substitutes for HOBt. Wiley-VCH Verlag GmbH & Co. KGaA.
Quantum chemistry-based interpretations on the lowest triplet state of luminescent lanthanides complexes. Part 1. Relation between the triplet state energy of hydroxamate complexes and their luminescence properties
Gutierrez, Fabien,Tedeschi, Christine,Maron, Laurent,Daudey, Jean-Pierre,Poteau, Romuald,Azema, Joelle,Tisnes, Pierre,Picard, Claude
, p. 1334 - 1347 (2007/10/03)
In this paper, we evaluate the potential use of theoretical calculations to obtain an energy scale of the lowest ligand-centred triplet excited state in luminescent terbium(m) complexes. In these complexes, non-radiative deactivation of the terbium emitti
Novel 1,4-benzodiazepines from acylnitroso-derived hetero-Diels-Alder cycloadducts
Surman, Matthew D.,Mulvihill, Mark J.,Miller, Marvin J.
, p. 139 - 141 (2007/10/03)
(matrix presented) N4-Hydroxy-1,4-benzodiazepines were synthesized in a single step from synthetically versatile acylnitroso-derived hetero-Diels-Alder cycloadducts. The efficiency of this transformation was found to be dependent on the NH pKa Of the cycloadduct sulfonamide.
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.
