474018-94-5

Upstream product

• 453-71-4 3-nitro-4-fluorobenzoic acid 
• 109-89-7 diethylamine 
• 400-94-2 4-fluoro-3-nitrobenzoyl chloride 

Downstream Products

• 474019-01-7 N,N-diethyl-4-[(2-methoxy-ethyl)amino]-3-nitro-benzamide 
• 474019-20-0 N,N-diethyl-4-(methylamino)-3-nitro-benzamide 
• 474019-50-6 4-{[2-(dimethylamino)ethyl]amino}-N,N-diethyl-3-nitro-benzamide 
• 476659-82-2 ethyl {4-[(diethylamino)carbonyl]-2-nitrophenyl} (quinolin-2(1H)-ylidene)acetate 
• 1046140-21-9 C₁₇H₂₀N₄O₃ 
• 474019-72-2 C₁₇H₂₀N₄O₃ 
• 474019-67-5 3-amino-N,N-diethyl-4-(isopentylamino)benzamide 
• 474015-61-7 2-(4-ethoxybenzyl)-N,N-diethyl-1-isopentyl-1H-benzo[d]imidazole-5-carboxamide 

Relevant academic research and scientific papers

Dual-Acting Cholinesterase-Human Cannabinoid Receptor 2 Ligands Show Pronounced Neuroprotection in Vitro and Overadditive and Disease-Modifying Neuroprotective Effects in Vivo

We have designed and synthesized a series of 14 hybrid molecules out of the cholinesterase (ChE) inhibitor tacrine and a benzimidazole-based human cannabinoid receptor subtype 2 (hCB2R) agonist and investigated them in vitro and in vivo. The compounds are potent ChE inhibitors, and for the most promising hybrids, the mechanism of human acetylcholinesterase (hAChE) inhibition as well as their ability to interfere with AChE-induced aggregation of β-amyloid (Aβ), and Aβ self-aggregation was assessed. All hybrids were evaluated for affinity and selectivity for hCB1R and hCB2R. To ensure that the hybrids retained their agonist character, the expression of cAMP-regulated genes was quantified, and potency and efficacy were determined. Additionally, the effects of the hybrids on microglia activation and neuroprotection on HT-22 cells were investigated. The most promising in vitro hybrids showed pronounced neuroprotection in an Alzheimer's mouse model at low dosage (0.1 mg/kg, i.p.), lacking hepatotoxicity even at high dose (3 mg/kg, i.p.).

CANNABINOID RECEPTOR SUBTYPE 2 STIMULATOR INHIBITING ACETYLCHOLINESTERASE AND BUTYRYLCHOLINESTERASE

The invention concerns a compound according to formula wherein R6 is H or an alkyl and one of R5 and R7 comprises or consists of linker-coupled tacrine residue wherein the linker is coupled to the amino residue of the tacrine residue and couples the tacrine residue to the rest of the molecule, wherein the other one of R5 and R7 is H or an alkyl.

Structure-Activity Relationships and Computational Investigations into the Development of Potent and Balanced Dual-Acting Butyrylcholinesterase Inhibitors and Human Cannabinoid Receptor 2 Ligands with Pro-Cognitive in Vivo Profiles

The enzyme butyrylcholinesterase (BChE) and the human cannabinoid receptor 2 (hCB2R) represent promising targets for pharmacotherapy in the later stages of Alzheimer's disease. We merged pharmacophores for both targets into small benzimidazole-based molecules, investigated SARs, and identified several dual-acting ligands with a balanced affinity/inhibitory activity and an excellent selectivity over both hCB1R and hAChE. A homology model for the hCB2R was developed based on the hCB1R crystal structure and used for molecular dynamics studies to investigate binding modes. In vitro studies proved hCB2R agonism. Unwanted μ-opioid receptor affinity could be designed out. One well-balanced dual-acting and selective hBChE inhibitor/hCB2R agonist showed superior in vivo activity over the lead CB2 agonist with regards to cognition improvement. The data shows the possibility to combine a small molecule with selective and balanced GPCR-activity/enzyme inhibition and in vivo activity for the therapy of AD and may help to rationalize the development of other dual-acting ligands.

Aminobenzimidazoles and Structural Isomers as Templates for Dual-Acting Butyrylcholinesterase Inhibitors and hCB2R Ligands To Combat Neurodegenerative Disorders

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

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

3-QUINOLINE-2-(1H)-YLIDENEINDOLIN-2-ONE DERIVATIVES

There is provided medicaments, particularly a vascular endothelial growth factor (VEGF) inhibitor which is useful as a therapeutic drug for solid tumors, diabetic retinopathy and the like diseases in which angiogenesis is taking a role. That is, since a novel 3-quinolin-2(1H)-ylideneindolin-2-one derivative or a salt thereof has good VEGF inhibitory action, angiogenesis inhibitory action and anti-tumor action, it is useful as ideal VEGF inhibitor, angiogenesis inhibitor and anti-tumor agent.