62992-68-1

Usage

Uses

Used in Pharmaceutical Industry:
1-Benzylpiperidine-4-carboxyamide is used as a building block for the synthesis of various drug molecules due to its versatile chemical structure and potential pharmacological properties.
Used in Central Nervous System Stimulants:
1-Benzylpiperidine-4-carboxyamide is used as a central nervous system stimulant for its potential to enhance cognitive function and alertness, although further research is required to confirm its efficacy and safety in this application.
Used in Analgesics:
1-Benzylpiperidine-4-carboxyamide is used as an analgesic agent for its potential to provide pain relief, although more studies are needed to determine its effectiveness and appropriate dosages for this purpose.

Upstream product

• 3612-20-2 1-phenylmethyl-4-piperidone 
• 77287-34-4 formamide 
• 39546-32-2 4-carboxamidopiperidine 
• 100-39-0 benzyl bromide 
• 100-44-7 benzyl chloride 
• 10315-06-7 1-benzylpiperidine-4-carboxylic acid methyl ester 
• 498-94-2 isonipecotic acid 
• 7462-86-4 methyl piperidine-4-carboxylate hydrochloride 
• 584-08-7 potassium carbonate 

Downstream Products

• 50541-93-0 4-amino-1-benzylpiperidine 
• 62718-31-4 1-benzylpiperidine-4-carbonitrile 
• 88915-26-8 4-aminomethyl-1-benzylpiperidine 
• 86542-94-1 1-(piperidine-4-yl)-propan-1-one 
• 86542-97-4 Cyclohexyl-piperidin-4-yl-methanone 
• 88796-05-8 1-(1-Benzyl-piperidin-4-yl)-propan-1-one 
• 88796-07-0 1-(1-Benzyl-piperidin-4-yl)-pentan-1-one 
• 86542-84-9 (1-benzylpiperidin-4-yl)(cyclopentyl)methanone 
• 76315-69-0 [1-(phenylmethyl)-4-piperidinyl] (thien-2-yl)-methanone 
• 86543-30-8 N-(2-Cyano-4,5-dimethoxy-phenyl)-4-(1-hydroxy-pentyl)-piperidine-1-carboximidothioic acid methyl ester 
• 80030-66-6 N-(2-Cyano-4,5-dimethoxy-phenyl)-4-propionyl-piperidine-1-carboximidothioic acid methyl ester 
• 86543-23-9 4-(1-Hydroxy-pentyl)-piperidine-1-carbothioic acid (2-cyano-4,5-dimethoxy-phenyl)-amide 
• 86543-17-1 4-Propionyl-piperidine-1-carbothioic acid (2-cyano-4,5-dimethoxy-phenyl)-amide 
• 80030-67-7 N-(2-Cyano-4,5-dimethoxy-phenyl)-4-pentanoyl-piperidine-1-carboximidothioic acid methyl ester 

Relevant academic research and scientific papers

Synthesis method of N-benzyl-4-piperidine formaldehyde

The invention belongs to the technical field of medicine synthesis, and particularly relates to a synthesis method of N-benzyl-4-piperidine formaldehyde. According to the invention, 4-piperidinecarboxylic acid is used as a raw material; an esterification reaction is carried out to generate 4-methyl piperidinecarboxylate hydrochloride; an alkylation reaction is carried out on N-benzyl-4-methyl piperidinecarboxylate hydrochloride to generate N-benzyl-4-methyl piperidinecarboxylate; n-benzyl-4-methyl piperidinecarboxylate is hydrolyzed to obtain N-benzyl-4-piperidinecarboxylic acid, N-benzyl-4-piperidinecarboxylic acid is subjected to an acylation reaction to generate N-benzyl-4-piperidinecarboxamide, N-benzyl-4-piperidinecarboxamide is dehydrated to obtain 1-benzylpiperidine-4-nitrile, and 1-benzylpiperidine-4-nitrile is subjected to a reduction reaction to generate N-benzyl-4-piperidineformaldehyde. The method is mild in reaction condition, simple in aftertreatment and high in yield, N-benzyl-4-piperidinecarboxaldehyde can be obtained at the high yield at the temperature of 0 DEG C, column chromatography is not needed, and repeatability is high.

Design, synthesis, and evaluation of acetylcholinesterase and butyrylcholinesterase dual-target inhibitors against Alzheimer’s diseases

A series of novel compounds 6a–h, 8i–1, 10s–v, and 16a–d were synthesized and evaluated, together with the known analogs 11a–f, for their inhibitory activities towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The inhibitory activities of AChE and BChE were evaluated in vitro by Ellman method. The results show that some compounds have good inhibitory activity against AChE and BChE. Among them, compound 8i showed the strongest inhibitory effect on both AChE (eeAChE IC50 = 0.39 μM) and BChE (eqBChE IC50 = 0.28 μM). Enzyme inhibition kinetics and molecular modeling studies have shown that compound 8i bind simultaneously to the peripheral anionic site (PAS) and the catalytic sites (CAS) of AChE and BChE. In addition, the cytotoxicity of compound 8i is lower than that of Tacrine, indicating its potential safety as anti-Alzheimer’s disease (anti-AD) agents. In summary, these data suggest that compound 8i is a promising multipotent agent for the treatment of AD.

Benzylpiperidine-benzimidazole derivative or pharmaceutically acceptable salt thereof, and preparation method and application thereof

The invention discloses a benzylpiperidine-benzimidazole derivative with a structure as shown in a general formula (I) or a pharmaceutically acceptable salt thereof, and a preparation method and application thereof. The derivative disclosed by the invention has good cholinesterase inhibition activity, can be used for preparing cholinesterase inhibitors, and is of important significance to treatment of neurodegenerative diseases.

Design, synthesis, in vitro and in vivo evaluation of benzylpiperidine-linked 1,3-dimethylbenzimidazolinones as cholinesterase inhibitors against Alzheimer’s disease

Cholinesterase inhibitor plays an important role in the treatment of patients with Alzheimer’s disease (AD). Herein, we report the medicinal chemistry efforts leading to a new series of 1,3-dimethylbenzimidazolinone derivatives. Among the synthesised compounds, 15b and 15j showed submicromolar IC50 values (15b, eeAChE IC50 = 0.39 ± 0.11 μM; 15j, eqBChE IC50 = 0.16 ± 0.04 μM) towards acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Kinetic and molecular modelling studies revealed that 15b and 15j act in a competitive manner. 15b and 15j showed neuroprotective effect against H2O2-induced oxidative damage on PC12 cells. This effect was further supported by their antioxidant activity determined in a DPPH assay in vitro. Morris water maze test confirmed the memory amelioration effect of the two compounds in a scopolamine-induced mouse model. Moreover, the hepatotoxicity of 15b and 15j was lower than tacrine. In summary, these data suggest 15b and 15j are promising multifunctional agents against AD.

Highly potent and selective aryl-1,2,3-triazolyl benzylpiperidine inhibitors toward butyrylcholinesterase in Alzheimer's disease

Acetylcholinesterase (AChE) is the key enzyme targeted in Alzheimer's disease (AD) therapy, nevertheless butyrylcholinesterase (BuChE) has been drawing attention due to its role in the disease progression. Thus, we aimed to synthesize novel cholinesterases inhibitors considering structural differences in their peripheral site, exploiting a moiety replacement approach based on the potent and selective hAChE drug donepezil. Hence, two small series of N-benzylpiperidine based compounds have successfully been synthesized as novel potent and selective hBuChE inhibitors. The most promising compounds (9 and 11) were not cytotoxic and their kinetic study accounted for dual binding site mode of interaction, which is in agreement with further docking and molecular dynamics studies. Therefore, this study demonstrates how our strategy enabled the discovery of novel promising and privileged structures. Remarkably, compound 11 proved to be one of the most potent (0.17 nM) and selective (>58,000-fold) hBuChE inhibitor ever reported.

Synthesis of novel substituted pyrimidine derivatives bearing a sulfamide group and their in vitro cancer growth inhibition activity

The synthesis of two series of novel substituted pyrimidine derivatives bearing a sulfamide group have been described and their in vitro cancer growth inhibition activities have been evaluated against three human tumour cell lines (HT-29, M21, and MCF7). In general, growth inhibition activity has been enhanced by the introduction of a bulky substituent on the aromatic ring with the best compound having GI50??6?μM for all the human tumour cell lines. The MCF7 selective compounds were evaluated on four additional human invasive breast ductal carcinoma cell lines (MDA-MB-231, MDA-MB-468, SKBR3, and T47D) and were selective against T47D cell line in all cases except one, suggesting a potential antiestrogen activity.

Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer's Agents: Synthesis and Biological Evaluation

A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 ± 0.01 μM) for AChE and (1.84 ± 0.03 μM) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced Aβ1-42 aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing Aβ1-42-induced toxicity by attenuating abnormal levels of Aβ1-42, p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

Synthesis of Nitriles from Aldoximes and Primary Amides Using XtalFluor-E

The dehydration reaction of aldoximes and amides for the synthesis of nitriles using [Et2NSF2]BF4 (XtalFluor-E) is described. Overall, the reaction proceeds rapidly (normally 1 h) at room temperature in an environmentally benign solvent (EtOAc) with only a slight excess of the dehydrating agent (1.1 equiv). A broad scope of nitriles can be prepared, including chiral nonracemic ones. In addition, in a number of cases, further purification of the nitrile after the workup was not required.

Synthesis of isocyanides through dehydration of formamides using XtalFluor-E

The formation of isocyanides from formamides using XtalFluor-E, [Et2NSF2]BF4, is presented. A wide range of formamides can be used to produce the corresponding isocyanides in up to 99% yield. In a number of cases, the crude products showed good purity (generally >80% by NMR) allowing to be used directly in multi-component reactions.

NOVEL COMPOUNDS

This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.