2735-73-1Relevant academic research and scientific papers
Design of benzimidazole- and benzoxazole-2-thione derivatives as inhibitors of bacterial hyaluronan lyase
Braun, Stephan,Botzki, Alexander,Salmen, Sunnhild,Textor, Christian,Bernhardt, Günther,Dove, Stefan,Buschauer, Armin
experimental part, p. 4419 - 4429 (2011/11/06)
Bacterial hyaluronan lyases (Hyal) degrade hyaluronan, an important component of the extracellular matrix, and are involved in microbial spread. Hyal inhibitors may serve as tools to study the role of the enzyme, its substrates and products in the course of bacterial infections. Moreover, such enzyme inhibitors are potential candidates for antibacterial combination therapy. Based on crystal structures of Streptococcus pneumoniae Hyal in complex with a hexasaccharide substrate and with different inhibitors, 1-acylated benzimidazole-2-thiones and benzoxazole-2-thiones were derived as new leads for the inhibition of Streptococcus agalactiae strain 4755 Hyal. Structure-based optimization led to N-(3-phenylpropionyl)benzoxazole-2-thione, one of the most potent compounds known to date (IC50 values: 24 μM at pH 7.4, 15 μM at pH 5). Among the 27 new derivatives, other N-acylated benzimidazoles and benzoxazoles are just as active at pH 7.4, but not at pH 5. The results support a binding mode characterized by interactions with residues in the catalytic site and with a hydrophobic patch.
Inhibitors of the salicylate synthase (Mbti) from Mycobacterium tuberculosis discovered by high-throughput screening
Vasan, Mahalakshmi,Neres, Joao,Williams, Jessica,Wilson, Daniel J.,Teitelbaum, Aaron M.,Remmel, Rory P.,Aldrich, Courtney C.
scheme or table, p. 2079 - 2087 (2011/11/29)
A simple steady-state kinetic high-throughput assay was developed for the salicylate synthase MbtI from Mycobacterium tuberculosis, which catalyzes the first committed step of mycobactin biosynthesis. The mycobactins are small-molecule iron chelators produced by M. tuberculosis, and their biosynthesis has been identified as a promising target for the development of new antitubercular agents. The assay was miniaturized to a 384-well plate format and high-throughput screening was performed at the National Screening Laboratory for the Regional Centers of Excellence in Biodefense and Emerging Infectious Diseases (NSRB). Three classes of compounds were identified comprising the benzisothiazolones (class I), diarylsulfones (class II), and benzimidazole-2-thiones (class III). Each of these compound series was further pursued to investigate their biochemical mechanism and structure-activity relationships. Benzimidazole-2-thione 4 emerged as the most promising inhibitor owing to its potent reversible inhibition.
1,3-Dihydro-1,3-diacetyl-2H-benzimidazol-2-one: A new versatile and selective acetylating agent
Chung, In Hwa,Cha, Ki Suk,Seo, Jae Hong,Kim, Joong Hyup,Chung, Bong Young,Kim, Choong Sup
, p. 529 - 533 (2007/10/03)
1,3-Dihydro-1,3-diacetyl-2H-benzimidazol-2-one (4, DABI) was proven to be a versatile and selective acetylating agent for amines. Selectivity and reactivity are not only superior than those of other known acetylating agents, but also products could be easily separated with excellent yield.
α-amidoalkylation reactions and oxidation of adducts of benzimidazoles and acyl chlorides
Venkov, Atanas P.,Statkova-Abeghe, Stela
, p. 1857 - 1864 (2007/10/03)
Adducts 4 of benzimidazoles and acyl chlorides were successfully used as electrophilic reagents in an intermolecular α-amidoalkylation reaction toward ketones for synthesis of 2-(2-oxoalkyl)-1,3-diacyl-2,3- dihydrobenzimidazoles 6 and oxidized with KMnO4 to 1,3-diacyl-2,3- dihydrobenzimidazol-2-ones 7.
