- A practical method, NaOCl-mediated, to prepare thiabendazoles via intramolecular amination reaction
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A series of new chlorinated thiabendazoles (6a–m) have been synthesized from readily available anilines and 4-cyanothiazole in moderate to good yields. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, IR, and mass spectrometry. Additionally, the structure of the compound (6f) was confirmed by single-crystal X-ray diffraction. In addition, synthesis of 2-substituted benzimidazoles and 2-phenyl benzothiazole was investigated using our optimized conditions and the outcome is presented herein.
- Patil, Vikrant,Barragan, Enrique,Patil, Shivaputra A.,Patil, Siddappa A.,Bugarin, Alejandro
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- Synthesis and biological evaluation of novel benzimidazole derivatives and analogs targeting the NLRP3 inflammasome
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A series of benzo[d]imidazole analogues of thiabenzole were synthesized and their anti-inflammatory activities toward NLRP3 (nucleotide-binding domain leucine-rich repeat containing protein family, pyrin domain-containing 3, also known as cryopyrin or NALP3) inflammasome were evaluated in vitro. Two lead compounds, TBZ-09 and TBZ-21, were identified by anti-production of IL-1β. In the second round of biological evaluation, based on the lead, 34 more compounds were synthesized and their in vitro anti-inflammatory activities were investigated. Several compounds were identified as anti-inflammatory agents that can reduce IL-1β expression in a dose-dependent manner. A preliminary structure-activity relationship is also summarized here.
- Pan, Liangkun,Hang, Nan,Zhang, Chao,Chen, Yu,Li, Shuchun,Sun, Yang,Li, Zhongjun,Meng, Xiangbao
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- Metal-mediated inhibition of escherichia coli methionine aminopeptidase: Structure-activity relationships and development of a novel scoring function for metal-ligand interactions
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We report the discovery of thiabendazole as a potent inhibitor (K 1 = 0.4 μM) of Escherichia coli methionine aminopeptidase (ecMetAP) and the synthesis and pharmacological evaluation of thiabendazole congeners with activity in the upper nanomolar range, Elucidation of the X-ray structure of ecMetAP in complex with thiabendazole and an unrelated inhibitor that was independently described by another group showed that that both compounds bind to an additional CoII ion at the entrance of the active site. This unexpected finding explains the inactivity of the compounds under in vivo conditions. It also allows us to discuss the structure-activity relationships of this series of compounds in a meaningful way, based upon docking runs with an auxiliary metal ion, We describe a new scoring function for the evaluation of metal-mediated inhibitor binding that, unlike the previously used scoring function implemented in the docking program, allows us to distinguish between active and inactive compounds, Finally, conclusions for the structure-based design of in vivo-active inhibitors of ecMetAP are drawn.
- Schiffmann, Rolf,Neugebauer, Alexander,Klein, Christian D.
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p. 511 - 522
(2007/10/03)
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