474015-61-7Relevant academic research and scientific papers
Aminobenzimidazoles and Structural Isomers as Templates for Dual-Acting Butyrylcholinesterase Inhibitors and hCB2R Ligands To Combat Neurodegenerative Disorders
Dolles, Dominik,Nimczick, Martin,Scheiner, Matthias,Ramler, Jacqueline,Stadtmüller, Patricia,Sawatzky, Edgar,Drakopoulos, Antonios,Sotriffer, Christoph,Wittmann, Hans-Joachim,Strasser, Andrea,Decker, Michael
supporting information, p. 1270 - 1283 (2016/07/27)
A pharmacophore model for butyrylcholinesterase (BChE) inhibitors was applied to a human cannabinoid subtype 2 receptor (hCB2R) agonist and verified it as a first-generation lead for respective dual-acting compounds. The design, synthesis, and pharmacological evaluation of various derivatives led to the identification of aminobenzimidazoles as second-generation leads with micro- or sub-micromolar activities at both targets and excellent selectivity over hCB1and AChE, respectively. Computational studies of the first- and second-generation lead structures by applying molecular dynamics (MD) on the active hCB2R model, along with docking and MD on hBChE, has enabled an explanation of their binding profiles at the protein levels and opened the way for further optimization. Dual-acting compounds with “balanced” affinities and excellent selectivities could be obtained that represent leads for treatment of both cognitive and pathophysiological impairment occurring in neurodegenerative disorders.
Synthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB2R selective benzimidazoles reveal unexpected intrinsic properties
Nimczick, Martin,Pemp, Daniela,Darras, Fouad H.,Chen, Xinyu,Heilmann, Joerg,Decker, Michael
supporting information, p. 3938 - 3946 (2014/08/18)
The design of bivalent ligands targeting G protein-coupled receptors (GPCRs) often leads to the development of new, highly selective and potent compounds. To date, no bivalent ligands for the human cannabinoid receptor type 2 (hCB2R) of the end
Novel benzimidazole derivatives as selective CB2 agonists
Pagé, Daniel,Balaux, Elise,Boisvert, Luc,Liu, Ziping,Milburn, Claire,Tremblay, Maxime,Wei, Zhongyong,Woo, Simon,Luo, Xuehong,Cheng, Yun-Xing,Yang, Hua,Srivastava, Sanjay,Zhou, Fei,Brown, William,Tomaszewski, Miroslaw,Walpole, Christopher,Hodzic, Leila,St-Onge, Stéphane,Godbout, Claude,Salois, Dominic,Payza, Keymal
scheme or table, p. 3695 - 3700 (2009/04/04)
The preparation and evaluation of a novel class of CB2 agonists based on a benzimidazole moiety are reported. They showed binding affinities up to 1 nM towards the CB2 receptor with partial to full agonist potencies. They also demonstrated good to excellent selectivity (>1000-fold) over the CB1 receptor.
