51314-51-3Relevant articles and documents
The high-pressure S(N)AR reaction of N-p-fluorobenzyl-2- chlorobenzimidazole with amines; an approach to norastemizole and analogues
Barrett, Ian C.,Kerr, Michael A.
, p. 2439 - 2442 (1999)
N-p-fluorobenzyl-2-chlorobenzimidazole was treated under hyperbaric conditions with a variety of primary and secondary amines. The resulting S(N)Ar reaction proceeded smoothly to produce excellent yields of adducts in most cases. This methodology provides rapid access to astemizole, norastemizole and related analogues.
Identification and optimization of 2-aminobenzimidazole derivatives as novel inhibitors of TRPC4 and TRPC5 channels
Zhu, Yingmin,Lu, Yungang,Qu, Chunrong,Miller, Melissa,Tian, Jinbin,Thakur, Dhananjay P,Zhu, Jinmei,Deng, Zixin,Hu, Xianming,Wu, Meng,McManus, Owen B,Li, Min,Hong, Xuechuan,Zhu, Michael X.,Luo, Huai-Rong
, p. 3495 - 3509 (2015/07/02)
Background and Purpose Transient receptor potential canonical (TRPC) channels play important roles in a broad array of physiological functions and are involved in various diseases. However, due to a lack of potent subtype-specific inhibitors the exact roles of TRPC channels in physiological and pathophysiological conditions have not been elucidated. Experimental Approach Using fluorescence membrane potential and Ca2+ assays and electrophysiological recordings, we characterized new 2-aminobenzimidazole-based small molecule inhibitors of TRPC4 and TRPC5 channels identified from cell-based fluorescence high-throughput screening. Key Results The original compound, M084, was a potent inhibitor of both TRPC4 and TRPC5, but was also a weak inhibitor of TRPC3. Structural modifications of the lead compound resulted in the identification of analogues with improved potency and selectivity for TRPC4 and TRPC5 channels. The aminobenzimidazole derivatives rapidly inhibited the TRPC4- and TRPC5-mediated currents when applied from the extracellular side and this inhibition was independent of the mode of activation of these channels. The compounds effectively blocked the plateau potential mediated by TRPC4-containing channels in mouse lateral septal neurons, but did not affect the activity of heterologously expressed TRPA1, TRPM8, TRPV1 or TRPV3 channels or that of the native voltage-gated Na+, K+ and Ca2+ channels in dissociated neurons. Conclusions and Implications The TRPC4/C5-selective inhibitors developed here represent novel and useful pharmaceutical tools for investigation of physiological and pathophysiological functions of TRPC4/C5 channels.
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.
