361979-66-0

Upstream product

• 31252-42-3 4-benzylpyperidine 
• 105-39-5 chloroacetic acid ethyl ester 
• 105-36-2 ethyl bromoacetate 
• 2905-56-8 N-Benzylpiperidine 

Downstream Products

• 414894-62-5 2-(4-benzylpiperidin-1-yl)acetohydrazide 
• 1418279-59-0 N'-(3,4-dimethoxybenzylidene)-2-(4-benzylpiperidin-1-yl)acetohydrazide 
• 1075725-65-3 N'-(3-allyl-2-hydroxybenzylidene)-2-(4-benzylpiperidin-1-yl)acetohydrazide 
• 1075725-67-5 N'-(3-allyl-2-hydroxybenzyl)-2-(4-benzylpiperazin-1-yl)acetohydrazide 
• 540483-73-6 N₁-(2-phenylethyl)-(2R)-2-{[(4-benzylpiperidino)methyl]carboxamido}-3-[1-(tert-butoxycarbonyl)-3-indolyl]propanamide 
• 685841-33-2 2-[(4-benzylpiperidin-1-yl)methyl]-5-methoxybenzimidazole 
• 159557-23-0 2-(4-Benzyl-piperidin-1-ylmethyl)-1H-benzimidazole 
• 438634-64-1 (4-benzylpiperidin-1-yl)-acetic acid 

Relevant academic research and scientific papers

Mapping the high-affinity binding domain of 5-substituted benzimidazoles to the proximal N-terminus of the GluN2B subunit of the NMDA receptor

Background and purpose: N-methyl-D-aspartate (NMDA) receptors represent an attractive drug target for the treatment of neurological and neurodegenerative disorders associated with glutamate-induced excitotoxicity. The aim of this study was to map the bind

Synthesis, molecular modeling and evaluation of novel N′-2-(4- benzylpiperidin-/piperazin-1-yl)acylhydrazone derivatives as dual inhibitors for cholinesterases and Aβ aggregation

To develop new drugs for treatment of Alzheimer's disease, a group of N′-2-(4-Benzylpiperidin-/piperazin-1-yl)acylhydrazones was designed, synthesized and tested for their ability to inhibit acetylcholinesterase, butyrylcholinesterase and aggregation of a

DESIGN, SYNTHESIS AND EVALUATION OF PROCASPASE ACTIVATING COMPOUNDS AS PERSONALIZED ANTI-CANCER DRUGS

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed that have lower neurotoxicity effects than other compounds.

Procaspase-3 activation as an anti-cancer strategy: Structure-activity relationship of procaspase-activating compound 1 (PAC-1) and its cellular co-localization with caspase-3

A goal of personalized medicine as applied to oncology is to identify compounds that exploit a defined molecular defect in a cancerous cell. A compound called procaspase-activating compound 1 (PAC-1) was reported that enhances the activity of procaspase-3 in vitro and induces apoptotic death in cancer cells in culture and inmouse xenograft models. Experimental evidence indicates that PAC-1 activates procaspase-3 in vitro through chelation of inhibitory zinc ions. Described herein is the synthesis and biological activity of a family of PAC-1 derivativeswhere key functional groups have been systematically altered. Analysis of these compounds reveals a strong correlation between the in vitro procaspase-3 activating effect and their ability to induce death in cancer cells in culture. Importantly, we also show that a fluorescently labeled version of PAC-1 co-localizes with sites of caspase-3 activity in cancer cells. The data presented herein further bolster the hypothesis that PAC-1 induces apoptosis in cancer cells through the direct activation of procaspase-3, has implications for the design and discovery of next-generation procaspase-3 activating compounds, and sheds light on the anti-apoptotic role of cellular zinc.

COMPOSITIONS AND METHODS INCLUDING CELL DEATH INDUCERS AND PROCASPASE ACTIVATION

Compositions and methods are disclosed in embodiments relating to induction of cell death such as in cancer cells. Compounds and related methods for synthesis and use thereof, including the use of compounds in therapy for the treatment of cancer and selective induction of apoptosis in cells are disclosed. Compounds are disclosed in connection with modification of procaspases such as procaspase-3. In embodiments, compositions are capable of activation of procaspase-3.

NR2B-Selective N-Methyl-D-aspartate Antagonists: Synthesis and Evaluation of 5-Substituted Benzimidazoles

Two classes of 5-substituted benzimidazoles were identified as potent antagonists of the NR2B subtype of the N-methyl-D-aspartate (NMDA) receptor. Selected compounds show very good selectivity versus the NR2A, NR2C, and NR2D subtypes of the NMDA receptor as well as versus hERG-channel activity and α1-adrenergic binding. Benzimidazole 37a shows excellent activity in the carrageenan-induced mechanical hyperalgesia assay in rats as well as good pharmacokinetic behavior in dogs.

2-[(4-BENZYL)-1-PIPERIDINYL)METHYL]BENZIMIDAZOLE-5-OL DERIVATIVES AS NR2B RECEPTOR ANTAGONISTS

2-[(4-Benzyl)-1-piperidinyl)-methyl]benzimidazole-5-ol derivatives are NMDA NR2B receptor antagonists useful in the treatment of pain and other NMDA mediated diseases.

Design of selective peptidomimetic agonists for the human orphan receptor BRS-3

New tool substances may help to unravel the physiological role of the human orphan receptor BRS-3 and its possible use as a drug target for the treatment of obesity and cancer. In continuation of our work on BRS-3, the solid- and solution-phase synthesis of a library of low molecular weight peptidomimetic agonists based on the recently developed short peptide agonist 4 is described. Functional potencies of the compounds were determined measuring calcium mobilization in a fluorometric imaging plate reader (FLIPR) assay. Focusing on the N-terminus, the D-Phe-Gln moiety of 4 was modified in a combinatorial SAR-oriented medicinal chemistry approach. With the incorporation of N-arylated glycine and alanine building blocks azaglycine, piperazine, or piperidine and the synthesis of semicarbazides and semicarbazones, a number of highly potent and selective compounds with a reduced number of peptide bonds were obtained, which also should have enhanced metabolic stability.

NON-PEPTIDIC BRS-3 AGONISTS

The invention relates to novel compounds having a selective BRS-3 agonistic action and corresponding to general formula (I) wherein A1, A2, A3, R1, R2, R3, Ar1, Ar2, Ar3, m and n have the designations cited in the description. The invention also relates to pharmaceuticals containing said compounds and to methods for producing compounds of formula (I).

Design, synthesis, and structure-activity relationships of a series of 3-[2-(1-benzylpiperidin-4-yl)ethylamino]pyridazine derivatives as acetylcholinesterase inhibitors

Starting from the 3-[2-(1-benzylpiperidin-4-yl)ethylamino]-6-phenylpyridazine 1, we performed the design, the synthesis, and the structure-activity relationships of a series of pyridazine analogues acting as AChE inhibitors. Structural modifications were achieved on four different parts of compound 1 and led to the following observations: (i) introduction of a lipophilic environment in the C-5 position of the pyridazine ring is favorable for the AChE-inhibitory activity and the AChE/BuChE selectivity; (ii) substitution and various replacements of the C-6 phenyl group are possible and led to equivalent or slightly more active derivatives; (iii) isosteric replacements or modifications of the benzylpiperidine moiety are detrimental to the activity. Among all derivatives prepared, the indenopyridazine derivative 4g was found to be the more potent inhibitor with an IC50 of 10 nM on electric eel AChE. Compared to compound 1, this represents a 12-fold increase in potency. Moreover, 3-[2-(1-benzylpiperidin-4-yl)ethylamino]-5-methyl-6-phenylpyridazine 4c, which showed an IC50 of 21 nM, is 100-times more selective for human AChE (human BuChE/AChE ratio of 24) than the reference compound tacrine.