17649-29-5Relevant academic research and scientific papers
New thiopyrimidine-benzenesulfonamide conjugates as selective carbonic anhydrase II inhibitors: synthesis, in vitro biological evaluation, and molecular docking studies
Abdel-Mohsen, Heba T.,Abdelsamie, Ahmed S.,Berrino, Emanuela,El Diwani, Hoda I.,El Kerdawy, Ahmed M.,Omar, Mohamed A.,Supuran, Claudiu T.
, (2020)
In the present work, a new series of thiopyrimidine-benzenesulfonamide conjugates was designed, synthesized and tested as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. Our design strategy was based on the molecular hybridization of the benzenesulfonamide moiety as a zinc binding group (ZBG), an alkylated thiopyrimidine moiety as a spacer and (un)substituted phenyl moieties with various electronic and hydrophobic environments as a tail. The designed and synthesized compounds were evaluated against four human (h) CA isoforms hCA I, hCA II, hCA IX and hCA XII. Series 6 showed promising activity and selectivity toward the cytosolic isoforms hCA I and hCA II versus the membrane bound isoforms hCA IX and hCA XII. Compounds 6e and 6f showed Ki of 0.04 μM against hCA II with a selectivity of 15.8- to 980-fold towards hCA II over hCA I, hCA IX, hCA XII isoforms. Molecular docking in the hCA II active site attributed the promising inhibitory activity of series 6 to the interaction of their sulfonamide moiety with the active site Zn2+ ion as well as its hydrogen bonding with the key amino acids Thr199 and Thr200. Through hydrophobic interaction, the benzenesulfonamide and the thiopyrimidine moieties interact with the hydrophobic side chains of the amino acids Val121/Leu198 and Ile91/Phe131, respectively. These results indicated that the designed and synthesized series is an interesting scaffold that can be further optimized for the development of selective antiglaucoma drugs.
On the Tautomerism of 2-Phenacyl-4-pyrimidinones and Related Compounds
Elguero, Jose,Goya, Pilar,Martinez, Ana,Rozas, Isabel
, p. 919 - 924 (2007/10/02)
3-Methyl-2-phenacyl-4-pyrimidinones 1, 2 have been synthesized using the sulfide contraction.According to the NMR data, the compounds 1, 2 exist exclusively as the benzoylmethylene tautomers a both in solution and in the solid state.AM1 calculations of the parent system are in agreement with the experimental observations.The study of the tautomeric equilibrium by this semiempirical method has been extended to other cases of enaminoketone/enolimine tautomerism. - Key Words: Pyrimidinones / Tautomerism / AM1 calculations
