604-50-2Relevant articles and documents
Quinazolines. 2*. unsymmetric 1,3-dialkyl-6-chlorosulfonyl- quinazoline-2,4-diones in nucleo- philic substitution reactions
Kuryazov,Mukhamedov,Shakhidoyatov
, p. 1508 - 1514 (2009)
The corresponding 6-chlorosulfonylquinazoline-2,4-diones were synthesized by the reactions of 1-methylquinazoline-2,4-dione and its 3-alkyl-substituted derivatives with chlorosulfonic acid. Treatment of the products with nucleophilic agents (water or ammo
Design, synthesis and biological evaluation of novel quinazoline-2,4-diones conjugated with different amino acids as potential chitin synthase inhibitors
Noureldin, Nada A.,Kothayer, Hend,Lashine, El-Sayed M.,Baraka, Mohamed M.,Huang, Yanrong,Li, Bing,Ji, Qinggang
, p. 560 - 569 (2018/05/24)
A series of (2-(1-methyl-2,4-dioxo-1,2-dihydroquinazolin-3(4H)-yl) acetamido) acids) (6 a-m), (7) has been designed to inhibit the action of fungus chitin synthase enzyme (CHS). The synthesis of the designed compounds was carried out in four steps starting from the reaction between 1-methylquinazoline-2,4(1H,3H)-dione and ethyl chloroacetate to yield the ethyl acetate derivative. This ester was hydrolyzed to the corresponding carboxylic acid derivative that was then utilized to couple several amino acids getting the final designed compounds. The synthesized compounds were tested for their inhibition against CHS. Compound 7 showed the highest potency among others with minimum inhibitory concentration (IC50) of 0.166 mmol/L, while polyoxin B (the positive control) had IC50 of 0.17 mmol/L. The synthesized compounds were also evaluated for their in vitro antifungal activity using Aspergillus fumigates, Aspergillus flavus, Crytococcus neoformans and Candida albicans. Unfortunately, the 14 synthesized compounds showed lower in vitro activity compared to the used active controls. However, compound 6m and fluconazole have synergistic effect on Aspergillus flavus; Compounds 7 and fluconazole have synergistic effects on Aspergillus fumigates.
Cell-Active Small Molecule Inhibitors of the DNA-Damage Repair Enzyme Poly(ADP-ribose) Glycohydrolase (PARG): Discovery and Optimization of Orally Bioavailable Quinazolinedione Sulfonamides
Waszkowycz, Bohdan,Smith, Kate M.,McGonagle, Alison E.,Jordan, Allan M.,Acton, Ben,Fairweather, Emma E.,Griffiths, Louise A.,Hamilton, Niall M.,Hamilton, Nicola S.,Hitchin, James R.,Hutton, Colin P.,James, Dominic I.,Jones, Clifford D.,Jones, Stuart,Mould, Daniel P.,Small, Helen F.,Stowell, Alexandra I. J.,Tucker, Julie A.,Waddell, Ian D.,Ogilvie, Donald J.
, p. 10767 - 10792 (2019/01/04)
DNA damage repair enzymes are promising targets in the development of new therapeutic agents for a wide range of cancers and potentially other diseases. The enzyme poly(ADP-ribose) glycohydrolase (PARG) plays a pivotal role in the regulation of DNA repair mechanisms; however, the lack of potent drug-like inhibitors for use in cellular and in vivo models has limited the investigation of its potential as a novel therapeutic target. Using the crystal structure of human PARG in complex with the weakly active and cytotoxic anthraquinone 8a, novel quinazolinedione sulfonamides PARG inhibitors have been identified by means of structure-based virtual screening and library design. 1-Oxetan-3-ylmethyl derivatives 33d and 35d were selected for preliminary investigations in vivo. X-ray crystal structures help rationalize the observed structure-activity relationships of these novel inhibitors.
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Paragraph 0450-0451, (2016/04/01)
Disclosed herein are compounds that bind to the vesicular monoamine transporter 2 (VMAT2), pharmaceutical compositions comprising those compounds, and methods of treatment using said compounds and pharmaceutical compositions.
