55022-82-7

Usage

Uses

Used in Pharmaceutical Research:
2-(1-benzylpiperidin-4-ylidene)acetonitrile is used as a potential drug candidate for the treatment of various neurological disorders and conditions. Its application is based on its potential to act as a central nervous system depressant and its capacity to interact with neurotransmitter receptors in the brain, which may contribute to its therapeutic effects.
Used in Medicinal Chemistry:
In the field of medicinal chemistry, 2-(1-benzylpiperidin-4-ylidene)acetonitrile is utilized for its chemical structure and pharmacological activity. The presence of the piperidine ring, benzyl group, and nitrile functional group are crucial for its interaction with biological targets, making it a valuable compound for the development of new medications aimed at treating neurological conditions.

Upstream product

• 41979-39-9 4-piperidone hydrochloride 
• 100-39-0 benzyl bromide 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 2537-48-6 diethyl 1-cyanomethylphosphonate 

Downstream Products

• 78056-67-4 1-(phenylmethyl)-4-piperidineacetonitrile 
• 86945-25-7 4-(2-aminoethyl)-1-(phenylmethyl)piperidine 
• 785783-14-4 [1-benzyl-4-(butylamino)piperidin-4-yl]acetonitrile 
• 1332498-42-6 2-(1-benzyl-piperidin-4-yl)-N-hydroxy-acetamidine 
• 1332498-43-7 N-[2-(1-benzyl-piperidin-4-yl)-1-hydroxyimino-ethyl]-3-(3,4-dimethoxy-phenyl)acrylamide 
• 1332498-44-8 1-benzyl-4-{5-[2-(3,4-dimethoxy-phenyl)-vinyl]-[1,2,4]oxadiazol-3-ylmethyl}piperidine 
• 1332498-45-9 4-{2-[3-(1-benzyl-piperidin-4-ylmethyl)-[1,2,4]oxadiazol-5-yl]-vinyl}-benzene-1,2-diol 
• 1333326-27-4 1-benzyl-4-[2-(3-thienylcarbonylamino)ethyl]piperidine 
• 1609078-45-6 N-[2-(1-benzylpiperidin-4-yl)ethyl]prop-2-yn-1-amine 
• 1609078-39-8 5-(((2-(1-benzylpiperidin-4-yl)ethyl)(prop-2-ynyl)amino)methyl)quinolin-8-ol 
• 120014-32-6 (1-benzylpiperidin-4-yl)acetaldehyde 
• 1609078-46-7 3-(1-benzylpiperidin-4-yl)-2-(prop-2-yn-1-ylamino)propanenitrile 
• 1609078-40-1 3-(1-benzylpiperidin-4-yl)-2-(((8-hydroxyquinolin-5-yl)methyl)(prop-2-ynyl)amino)propanenitrile 

Relevant academic research and scientific papers

Rhodium-Catalyzed 1,1-Hydroacylation of Thioacyl Carbenes with Alkynyl Aldehydes and Subsequent Cyclization

A rhodium-catalyzed 1,1-hydroacylation of thioacyl carbenes with alkynyl and alkenyl aldehydes and subsequent 6-endo-trig/dig cyclization are realized, giving structurally diverse 4H-thiopyran-4-ones and 2,3-dihydro-4H-thiopyran-4-ones in moderate to good yields. The oxidative addition of Rh(I) to aldehydes is proposed to be the turnover-limiting step. Manipulations of estrones demonstrate the applications of our formal (3 + 3) transannulations in the structural modifications of natural products.

Donepezil-like multifunctional agents: Design, synthesis, molecular modeling and biological evaluation

Currently available drugs against Alzheimer's disease (AD) are only able to ameliorate the disease symptoms resulting in a moderate improvement in memory and cognitive function without any efficacy in preventing and inhibiting the progression of the pathology. In an effort to obtain disease-modifying anti-Alzheimer's drugs (DMAADs) following the multifactorial nature of AD, we have recently developed multifunctional compounds. We herein describe the design, synthesis, molecular modeling and biological evaluation of a new series of donepezil-related compounds possessing metal chelating properties, and being capable of targeting different enzymatic systems related to AD (cholinesterases, ChEs, and monoamine oxidase A, MAO-A). Among this set of analogues compound 5f showed excellent ChEs inhibition potency and a selective MAO-A inhibition (vs MAO-B) coupled to strong complexing properties for zinc and copper ions, both known to be involved in the progression of AD. Moreover, 5f?exhibited moderate antioxidant properties as found by in?vitro assessment. This compound represents a novel donepezil–hydroxyquinoline hybrid with DMAAD profile paving the way to the development of a novel class of drugs potentially able to treat AD.

Multi-target-oriented protective agent neurocyte

PROBLEM TO BE SOLVED: To provide a promising multi target direction type pharmaceutical candidate molecule which is promising for treatments of Alzheimer-type dementia (AD), which is a molecule having good cell membrane permeability including blood brain barrier.SOLUTION: A compound designed by a conjunction method with which a benzylpiperidine part of an acetylcholine esterase (AChE) inhibitor, donepezil is connected through an oligomethylene linker and combined with a propargyl part having a monoamine oxidase(MAO) inhibition activity and 8-hydroxy-5-methylaminoquinoline functional group, i.e. a center nitrogen atom substituted by a pro-chelator motif of a biochemical metal, interacts with AChE and butyrylcholinesterase(BuChE), further MAOA and B.

Neuroprotective multi-target directed drugs

A new family of multitarget molecules able to interact with acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), as well as with monoamino oxidase (MAO) A and B, has been synthesized. Novel compounds have been designed using a conjunctive approach that combines the benzylpiperidine moiety of the AChE inhibitor donepezil, connected through an oligomethylene linker, to a central nitrogen atom substituted with the propargyl moiety responsible for the MAO inhibition, and a 8-hydroxy-5-methylaminoquinoline functional group, the biometal pro-chelator motif. Overall, the results suggest that the new compounds are promising multitarget drug candidates with potencial impact for AD therapy.

Donepezil + propargylamine + 8-hydroxyquinoline hybrids as new multifunctional metal-chelators, ChE and MAO inhibitors for the potential treatment of Alzheimer's disease

The synthesis, biochemical evaluation, ADMET, toxicity and molecular modeling of novel multi-target-directed Donepezil + Propargylamine + 8-Hydroxyquinoline (DPH) hybrids 1-7 for the potential prevention and treatment of Alzheimer's disease is described. The most interesting derivative was racemic α-aminotrile4-(1-benzylpiperidin-4-yl)-2-(((8-hydroxyquinolin-5-yl) methyl)(prop-2-yn-1-yl)amino) butanenitrile (DPH6) [MAO A (IC50 = 6.2 ± 0.7 μM; MAO B (IC50 = 10.2 ± 0.9 μM); AChE (IC50 = 1.8 ± 0.1 μM); BuChE (IC50 = 1.6 ± 0.25 μM)], an irreversible MAO A/B inhibitor and mixed-type AChE inhibitor with metal-chelating properties. According to docking studies, both DPH6 enantiomers interact simultaneously with the catalytic and peripheral site of EeAChE through a linker of appropriate length, supporting the observed mixed-type AChE inhibition. Both enantiomers exhibited a relatively similar position of both hydroxyquinoline and benzyl moieties with the rest of the molecule easily accommodated in the relatively large cavity of MAO A. For MAO B, the quinoline system was hosted at the cavity entrance whereas for MAO A this system occupied the substrate cavity. In this disposition the quinoline moiety interacted directly with the FAD aromatic ring. Very similar binding affinity values were also observed for both enantiomers with ChE and MAO enzymes. DPH derivatives exhibited moderate to good ADMET properties and brain penetration capacity for CNS activity. DPH6 was less toxic than donepezil at high concentrations; while at low concentrations both displayed a similar cell viability profile. Finally, in a passive avoidance task, the antiamnesic effect of DPH6 was tested on mice with experimentally induced amnesia. DPH6 was capable to significantly decrease scopolamine-induced learning deficits in healthy adult mice.

Synthesis and evaluation of multi-target-directed ligands against Alzheimer's disease based on the fusion of donepezil and ebselen

A novel series of compounds obtained by fusing the cholinesterase inhibitor donepezil and the antioxidant ebselen were designed as multi-target-directed ligands against Alzheimer's disease. An in vitro assay showed that some of these molecules did not exhibit highly potent cholinesterase inhibitory activity but did have various other ebselen-related pharmacological effects. Among the molecules, compound 7d, one of the most potent acetylcholinesterase inhibitors (IC50 values of 0.042 μM for Electrophorus electricus acetylcholinesterase and 0.097 μM for human acetylcholinesterase), was found to be a strong butyrylcholinesterase inhibitor (IC50 = 1.586 μM), to possess rapid H2O2 and peroxynitrite scavenging activity and glutathione peroxidase-like activity (ν0 = 123.5 μM min-1), and to be a substrate of mammalian TrxR. A toxicity test in mice showed no acute toxicity at doses of up to 2000 mg/kg. According to an in vitro blood-brain barrier model, 7d is able to penetrate the central nervous system.

OXADIAZOLE COMPOUNDS, THEIR PREPARATION AND USE

The present invention relates to oxadiazole compounds in all their stereoisomeric and tautomeric forms and mixtures thereof in all ratios; and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable prodrugs and pharmaceutically acceptable polymorphs. The invention also relates to processes for the manufacture of the oxadiazole compounds and to pharmaceutical compositions containing them. The said compounds and their pharmaceutical compositions are useful in the treatment of cancer, particularly chronic myeloid leukemia (CML). The present invention further provides a method of treatment of cancer by administering a therapeutically effective amount of said compounds or their pharmaceutical compositions, to a mammal in need thereof.

Synthesis of 1-benzyl-4-[2-(3-thienylcarbonylamino)ethyl]piperidine as a novel potential cholinesterase inhibitor

Potentiating of cholinergic activity which increases the acetylcholine level in the brain has been regarded as an approach for the palliative treatment of alzheimer's disease. Accordingly, inhibition of the acetyl cholinesterase enzyme is considered to be a viable and attractive therapeutic strategy for alzheimer's disease patients. In an attempt to find a new acetyl cholinesterase inhibitor (AChEI), 1-benzylpiperidin- 4-yl-ethylamine has been reacted with thiophen-3-carbonylchloride to prepare 1-benzyl-4-[2-(3-thienylcarbonyl-amino) ethyl]piperidine, as potential acetyl cholinesterase inhibitor. The structure of target compound was confirmed by mass, NMR and IR spectra.

Aminopyridazines as acetylcholinesterase inhibitors

Following the discovery of the weak, competitive and reversible acetylcholinesterase (AChE)-inhibiting activity of minaprine (3c) (IC50 = 85 μM on homogenized rat striatum AChE), a series of 3-amino-6- phenylpyridazines was synthesized and tested for inhibition of AChE. A classical structure-activity relationship exploration suggested that, in comparison to minaprine, the critical elements for high AChE inhibition are as follows: (i) presence of a central pyridazine ring, (ii) necessity of a lipophilic cationic head, (iii) change from a 2- to a 4-5-carbon units distance between the pyridazine ring and the cationic head. Among all the derivatives investigated, 3-[2-(1-benzylpiperidin-4-yl)ethylamino]-6- phenylpyridazine (3y), which shows an IC50 of 0.12 μM on purified AChE (electric eel), was found to be one of the most potent anti-AChE inhibitors, representing a 5000-fold increase in potency compared to minaprine.