78630-35-0Relevant academic research and scientific papers
Identification and Profiling of Hydantoins - A Novel Class of Potent Antimycobacterial DprE1 Inhibitors
Rogacki, Maciej K.,Pitta, Eleni,Balabon, Olga,Huss, Sophie,Lopez-Roman, Eva Maria,Argyrou, Argyrides,Blanco-Ruano, Delia,Cacho, Monica,Vande Velde, Christophe M. L.,Augustyns, Koen,Ballell, Lluis,Barros, David,Bates, Robert H.,Cunningham, Fraser,Van Der Veken, Pieter
supporting information, p. 11221 - 11249 (2019/01/08)
Tuberculosis is the leading cause of death worldwide from infectious diseases. With the development of drug-resistant strains of Mycobacterium tuberculosis, there is an acute need for new medicines with novel modes of action. Herein, we report the discovery and profiling of a novel hydantoin-based family of antimycobacterial inhibitors of the decaprenylphospho-β-d-ribofuranose 2-oxidase (DprE1). In this study, we have prepared a library of more than a 100 compounds and evaluated them for their biological and physicochemical properties. The series is characterized by high enzymatic and whole-cell activity, low cytotoxicity, and a good overall physicochemical profile. In addition, we show that the series acts via reversible inhibition of the DprE1 enzyme. Overall, the novel compound family forms an attractive base for progression to further stages of optimization and may provide a promising drug candidate in the future.
Solvent effects on the absorption spectra of potentially pharmacologically active 5-alkyl-5-arylhydantoins: A structure-property relationship study
Hmuda, Sleem F.,Banjac, Nebojsa R.,Trisovic, Nemanja P.,Bozic, Bojan D.,Valentic, Natasa V.,Uscumlic, Gordana S.
, p. 627 - 637 (2013/07/26)
To obtain insight into the interactions of potential anticonvulsant drugs with their surrounding, two series of 5-methyl-5-aryl- and 5-ethyl-5- -arylhydantoins were synthesized and their absorption spectra were recorded in the region from 200 to 400 nm in a set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima shifts were analyzed by means of the linear solvation energy relationship (LSER) concept of Kamlet and Taft. The ratio of the contributions of specific and non-specific solvent-solute interactions were correlated with the corresponding absorption, distribution, metabolism, and excretion (ADME) properties of the studied compounds. The correlation equations were combined with different physicochemical parameters to generate new equations, which demonstrate the reasonable relationships between the solvent- solute interactions and the structure-activity parameters. Copyright (C)2013 SCS.
Hydantoins having RNase modulatory activity
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Page/Page column 9, (2008/06/13)
The present invention relates to hydantoin derivatives having RNase H, polymerase and/or HIV reverse transcriptase modulatory, and particularly, inhibitory activity. Included in the invention are the hydantoin derivatives, compositions containing the deri
