2851-12-9Relevant articles and documents
Discovery of potent wall teichoic acid early stage inhibitors
Labroli, Marc A.,Caldwell, John P.,Yang, Christine,Lee, Sang Ho,Wang, Hao,Koseoglu, Sandra,Mann, Paul,Yang, Shu-Wei,Xiao, Jing,Garlisi, Charles G.,Tan, Christopher,Roemer, Terry,Su, Jing
, p. 3999 - 4002 (2016)
The widespread emergence of methicillin-resistant Staphylococcus aureus (MRSA) has dramatically eroded the efficacy of current β-lactam antibiotics and created an urgent need for novel treatment options. Using an S. aureus phenotypic screening strategy, we have identified small molecule early stage wall teichoic acid (WTA) pathway-specific inhibitors predicted to be chemically synergistic with β-lactams. These previously disclosed inhibitors, termed tarocins, demonstrate by genetic and biochemical means inhibition of TarO, the first step in WTA biosynthesis. Tarocins demonstrate potent bactericidal synergy in combination with broad spectrum β-lactam antibiotics across diverse clinical isolates of methicillin-resistant Staphylococci. The synthesis and structure–activity relationships (SAR) of a tarocin series will be detailed. Tarocins and other WTA inhibitors may provide a rational strategy to develop Gram-positive bactericidal β-lactam combination agents active against methicillin-resistant Staphylococci.
2,2'-DIALKOXY, 2,2'-DIHYDROXY, AND 2,2'-DIAMINO DERIVATIVES OF 1,1'-AZOBENZIMIDAZOLE. THE FIRST SYNTHESIS OF HETEROCYCLIC TETRAZENES BY MEANS OF A NUCLEOPHILIC SUBSTITUTION REACTION
Kuz'menko, V. V.,Nanavyan, I. M.,Pozharskii, A. F.
, p. 154 - 157 (1992)
2,2'-Dimethanesulfonyl-1,1'-azobenzimidazole is prepared by the oxidation of 1-amino-2-methanesulfonylbenzimidazole with lead tetraacetate.The reaction of this tetrazene with alkali in DMSO, with sodium alkoxides in the corresponding alcohol or ammonia, or with primary or secondary amines leads to the formation of 2,2'-dihydroxy, 2,2'-dialkoxy, or 2,2'-diamino derivatives of 1,1'-azobenzimidazole.
Eco-friendly strategy: design and synthesis of biologically potent benzimidazole-amine hybrids via visible-light generated oxidative C-H arylamylation of analenic amidines
Siddiqui,Ibad, Farah,Ibad, Afshan,Abdul Waseem, Malik,Watal, Geeta
, p. 5 - 10 (2016)
An operationally simple visible light mediated intramolecular cyclization of benzimidazole to 2-amino benzimidazole hybrid. The disclosed procedure is rapid and the convenient synthesis of benzimidazole-amine hybrids from easily available substituted cycl
Copper-catalysed C-H functionalisation gives access to 2-aminobenzimidazoles
Clark, Peter R.,Williams, Glynn D.,Tomkinson, Nicholas C. O.
, p. 7943 - 7955 (2019/09/06)
This paper describes the development, optimisation and exemplification of a copper-catalysed C-H functionalisation to form pharmaceutically relevant 2-aminobenzimidazoles from aryl-guanidines. High throughput screening was used as a tool to identify a catalytically active copper source, DoE was used for reaction optimisation and a range of aryl-guanidines were prepared and exposed to the optimum conditions to afford a range of 2-aminobenzimidazoles in moderate to good yields. The methodology has been applied to the synthesis of Emedastine, a marketed anti-histamine pharmaceutical compound, with the key cyclisation step performed on a gram-scale.
Benzimidazole derivative and preparation method and application thereof
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Paragraph 0052; 0053; 0054, (2019/01/08)
The invention discloses a benzimidazole derivative and a preparation method and the application thereof. The prepared benzimidazole derivative is capable of effectively reducing the relapse arte afterabstaining from morphine addiction, has a remarkable ef
Synthesis, biological evaluation and molecular modeling of substituted 2-aminobenzimidazoles as novel inhibitors of acetylcholinesterase and butyrylcholinesterase
Zhu, Jinmei,Wu, Chun-Feng,Li, Xiaobing,Wu, Gui-Sheng,Xie, Shan,Hu, Qian-Nan,Deng, Zixin,Zhu, Michael X.,Luo, Huai-Rong,Hong, Xuechuan
, p. 4218 - 4224 (2013/07/27)
A series of novel 2-aminobenzimidazole derivatives were synthesized under microwave irradiation. Their biological activities were evaluated on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). A number of the 2-aminobenzimidazole derivatives showed good inhibitory activities to AChE and BuChE. Among them, compounds 9, 12 and 13 were found to be >25-fold more selective for BuChE than AChE. No evidence of cytotoxicity was observed by MTT assay in PC12 cells or HepG2 cells exposed to 100 μM of the compounds. Molecular modeling studies indicate that the benzimidazole moiety of compounds 9, 12 and 13 forms a face-to-face π-π stacking interaction in a 'sandwich' form with the indole ring of Trp82 (4.09 A?) in the active gorge, and compounds 12 and 13 form a hydrogen bond with His438 at the catalytic site of BuChE. In addition, compounds 12 and 13 fit well into the hydrophobic pocket formed by Ala328, Trp430 and Tyr332 of BuChE. Our data suggest the 2-aminobenzimidazole drugs as promising new selective inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.
Chloroformamidinium salts: Efficient reagents for preparation of 2-aminobenzoimidazole, 2-aminobenzoxazole, and 2-aminobenzothiazole derivatives
El-Faham, Ayman,Chebbo, Mohamed,Abdul-Ghani, Mohamed,Younes, Ghassan
, p. 599 - 606 (2007/10/03)
A Reaction involving chloroformamidinium salts (TCFH 1a, BTCFH 1b, DmCFH 1c, DmPCFH 1d, BPCFH 1e) and 2-aminophenol 9a, benzene-1,2-diamine 9b, and 2-aminothiophenol 9c afforded 2-aminobenzoxazole 13, 2-aminobenzoimidazole 14, and 2-aminobenzothiazole 15 derivatives, respectively as major products, due to the in situ heterocyclization with dimethylamine acting as the better leaving group. Attempts for preparation of 13-15 from the reaction of N,N-dimethyl carbomyl chloride 16 with 2-aminophenol 9a, benzene-1,2-diamine 9b, and 2-aminothiophenol 9c were unsuccessful, and gave the unexpected products benzoxazol-2-ol 18a, benzoimidazol-2-one 18b, and S-(2-amino-phenyl) N,N-dimethylthiocarbamate 19 respectively. On the other hand reaction of chloroformamidinium salts 1a-e with 3-benzyl-2-hydrazinoquinoxaline 3 and 1-hydrazinophthalazine hydrochloride 4 in the presence of triethylamine as a base, afforded the [1,2,4]triazolo derivatives 6 and 7 respectively in good yield and purity. These triazole derivatives were formed due to the strong tendency towards heterocyclization and substitution of dimethylamine group as a better leaving group.
