- Bioisosteric modification of known fucosidase inhibitors to discover a novel inhibitor of α-l-fucosidase
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Bioisosteric modification of known fucosidase inhibitors A and B, resulted in three new types of molecules, 4b, 5c and 6a (belonging to furopyridinedione, thiohydantoin and hydantoin chemotypes) that could potentially bind to α-l-fucosidase (bovine kidney
- Bathula, Chandramohan,Ghosh, Shreemoyee,Hati, Santanu,Tripathy, Sayantan,Singh, Shailja,Chakrabarti, Saikat,Sen, Subhabrata
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p. 3563 - 3572
(2017/01/25)
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- Systematic Evaluation of the Metabolism and Toxicity of Thiazolidinone and Imidazolidinone Heterocycles
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The thiazolidine and imidazolidine heterocyclic scaffolds, i.e., the rhodanines, 2,4-thiazolidinediones, 2-thiohydantoins, and hydantoins have been the subject of debate on their suitability as starting points in drug discovery. This attention arose from the wide variety of biological activities exhibited by these scaffolds and their frequent occurrence as hits in screening campaigns. Studies have been conducted to evaluate their value in drug discovery in terms of their biological activity, chemical reactivity, aggregation-based promiscuity, and electronic properties. However, the metabolic profiles and toxicities have not been systematically assessed. In this study, a series of five-membered multiheterocyclic (FMMH) compounds were selected for a systematic evaluation of their metabolic profiles and toxicities on TAMH cells, a metabolically competent rodent liver cell line and HepG2 cells, a model of human hepatocytes. Our studies showed that generally the rhodanines are the most toxic, followed by the thiazolidinediones, thiohydantoins, and hydantoins. However, not all compounds within the family of heterocycles were toxic. In terms of metabolic stability, 5-substituted rhodanines and 5-benzylidene thiohydantoins were found to have short half-lives in the presence of human liver microsomes (t1/2 30 min) suggesting that the presence of the endocyclic sulfur and thiocarbonyl group or a combination of C5 benzylidene substituent and thiocarbonyl group in these heterocycles could be recognition motifs for P450 metabolism. However, the stability of these compounds could be improved by installing hydrophilic functional groups. Therefore, the toxicities and metabolic profiles of FMMH derivatives will ultimately depend on the overall chemical entity, and a blanket statement on the effect of the FMMH scaffold on toxicity or metabolic stability cannot and should not be made.
- Tang, Shi Qing,Lee, Yong Yang Irvin,Packiaraj, David Sheela,Ho, Han Kiat,Chai, Christina Li Lin
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p. 2019 - 2033
(2015/11/02)
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- Design and Synthesis of Novel Phenylpiperazine Derivatives as Potential Anticonvulsant Agents
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Eighteen new 5-benzylidene-3-(4-arylpiperazin-1-ylmethyl)-2-thioxo-imidazolidin-4-ones were designed as hybrid structures from previously reported anticonvulsant compounds, synthesized and tested for anticonvulsant activity. Initial anticonvulsant screeni
- Habib, Monica M. W.,Abdelfattah, Mohamed A. O.,Abadi, Ashraf H.
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p. 868 - 874
(2015/12/24)
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- (S)-5-Benzyl- and 5-benzylidene-imidazo-4-one derivatives synthesized and studied for an understanding of their thermal reactivity
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Flash vacuum as well as static pyrolysis were used to gain insight into the mechanisms of decomposition of the title compounds. They were synthesized by the use of microwave techniques that allowed better yields than the established methods. Since the benzyl compounds always open a radical channel in the thermal processes, consequently lowering the yields of other important intramolecular processes, we also started the pyrolysis with benzylidene derivatives. Detection and quantification of products accompanied by kinetic analyses were carried out for both types of compounds. The activation energies as well as the entropy contributions have been determined. Moreover, DFT calculations provided support for and corroborating of the proposed thermal pathways.
- Pepino,Pelez,Faillace,Ceballos,Moyano,Argüello
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p. 60092 - 60101
(2015/02/19)
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- SYNTHESIS OF IMIDAZOLE-2-THIONES VIA THIOHYDANTOINS
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The present invention provides a method of making an imidazole 2-thione which comprises the step(s) of reducing a thiohydantoin to said imidazole- 2-thione.
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Page/Page column 33
(2010/11/26)
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- Facile synthesis of 2-alkylthio-3-alkyl-5-phenylmethylidene-4H-imidazol-4- ones
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2-Alkylthio-3-alkyl-5-phenylmethylidene-4H-imidazol-4-ones 6 were synthesized by N-alkylation and S-alkylation of 2-thioxo-5-phenylmethylidene-4- imidazolidinone 5, which was obtained via cyclization of vinyl isothiocyanate 4 with excess ammonium hydroxid
- Sun, Yong,Gao, Li-Ping,Ding, Ming-Wu
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p. 1185 - 1191
(2007/10/03)
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- Glycine derivatives of imidazolones as potential ligands of glycine binding site of NMDA receptors. Part 1
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The series of glycine derivatives of diphenyl or (un)substituted arylidene imidazolones was designed and obtained as potential ligands of the glycine binding site of NMDA receptors. The compounds were evaluated in vitro for their affinity to the glycine b
- Kiec-Kononowicz, Katarzyna,Karolak-Wojciechowska, Janina,Handzlik, Jadwiga
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p. 381 - 388
(2007/10/03)
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- Thiazole derivatives
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New thiazole derivatives of the general formula I STR1 and their salts with physiologically acceptable acids are described as well as a process for their manufacture. The new compounds exhibit histamine H-2 antagonist activity and may thus be used to inhi
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