- Privileged scaffolds or promiscuous binders: A comparative study on rhodanines and related heterocycles in medicinal chemistry
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Rhodanines and related five-membered heterocycles with multiple heteroatoms have recently gained a reputation of being unselective compounds that appear as "frequent hitters" in screening campaigns and therefore have little value in drug discovery. However, this judgment appears to be based mostly on anecdotal evidence. Having identified various rhodanines and related compounds in screening campaigns, we decided to perform a systematic study on their promiscuity. An amount of 163 rhodanines, hydantoins, thiohydantoins, and thiazolidinediones were synthesized and tested against several targets. The compounds were also characterized with respect to aggregation and electrophilic reactivity, and the binding modes of rhodanines and related compounds in published X-ray cocrystal structures were analyzed. The results indicate that the exocyclic, double bonded sulfur atom in rhodanines and thiohydantoins, in addition to other structural features, offers a particularly high density of interaction sites for polar interactions and hydrogen bonds. This causes a promiscuous behavior at concentrations in the "screening range" but should not be regarded as a general knockout criterion that excludes such screening hits from further development. It is suggested that special criteria for target affinity and selectivity are applied to these classes of compounds and that their exceptional and potentially valuable biomolecular binding properties are consequently exploited in a useful way.
- Mendgen, Thomas,Steuer, Christian,Klein, Christian D.
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supporting information; experimental part
p. 743 - 753
(2012/03/11)
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- Synthesis and characterization of (Z)-5-arylmethylidenerhodanines with photosynthesis-inhibiting properties
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A series of rhodanine derivatives was prepared. The synthetic approach, analytical and spectroscopic data of all synthesized compounds are presented. Lipophilicity of all the discussed rhodanine derivatives was analyzed using the RP-HPLC method. The compo
- Opletalova, Veronika,Dolezel, Jan,Kralova, Katarina,Pesko, Matus,Kunes, Jiri,Jampilek, Josef
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experimental part
p. 5207 - 5227
(2011/08/06)
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- Selective small molecule inhibitors of the potential breast cancer marker, human arylamine N-acetyltransferase 1, and its murine homologue, mouse arylamine N-acetyltransferase 2
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The identification, synthesis and evaluation of a series of rhodanine and thiazolidin-2,4-dione derivatives as selective inhibitors of human arylamine N-acetyltransferase 1 and mouse arylamine N-acetyltransferase 2 is described. The most potent inhibitors
- Russell, Angela J.,Westwood, Isaac M.,Crawford, Matthew H.J.,Robinson, James,Kawamura, Akane,Redfield, Christina,Laurieri, Nicola,Lowe, Edward D.,Davies, Stephen G.,Sim, Edith
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experimental part
p. 905 - 918
(2009/09/25)
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- Microwave induced synthesis of the thiazolidine-2,4-dione motif and the efficient solvent free-solid phase parallel syntheses of 5-benzylidene- thiazolidine-2,4-dione and 5-benzylidene-2-thioxo-thiazolidine-4-one compounds
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Novel microwave induced method for the synthesis of thiazolidine-2,4-dione motif under solvent phase conditions is developed. Further we report an efficient, microwave assisted method for the parallel syntheses of biologically important 5-benzylidene-thiazolidine-2,4-dione and 5-benzylidene-2- thioxothiazolidine-4-one compounds under solid-phase and solvent-free conditions. A comparative study between the developed microwave methods and the conventional methods is described. We have also illustrated the possible mechanism behind to address the reason why piperidine, acetic acid and silica gel enhanced the Knoevenagel condensation reaction.
- Kumar, B. R. Prashantha,Karvekar,Adhikary,Nanjan,Suresh
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p. 897 - 903
(2007/10/03)
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- COMPOUNDS USEFUL AS HYPOGLYCEMIC AGENTS AND FOR TREATING ALZHEIMER'S DISEASE
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Provided are methods for treating hyperglycemia and Alzheimer's disease utilizing certain rhodanine derivatives. Certain of the rhodanine derivatives utilized in the instant methods are novel and, accordingly, such compounds and pharmaceutical formulation
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