705977-17-9Relevant 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).
3-Hydroxy-quinazoline-2,4-dione as a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists
Colotta, Vittoria,Catarzi, Daniela,Varano, Flavia,Calabri, Francesca Romana,Filacchioni, Guido,Costagli, Chiara,Galli, Alessandro
, p. 2345 - 2349 (2007/10/03)
The synthesis and Gly/NMDA, AMPA and KA receptor binding activities of some 3-hydroxy-quinazoline-2,4-dione derivatives are reported. The binding data, together with functional antagonism studies, showed that the 3-hydroxy-quinazoline-2,4-dione moiety can be considered a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists. In fact, introduction of chlorine atom(s) on precise position(s) of the benzofused moiety yielded Gly/NMDA selective antagonists, while the presence of the 6-(1,2,4-triazol-4-yl) group shifted the affinity and selectivity towards the AMPA receptor.
