76733-91-0

Upstream product

• 110-89-4 piperidine 
• 66110-15-4 (2E,4E)-5-(4-methoxyphenyl)-1-(piperidine-1-yl)penta-2,4-dien-1-one 
• 3626-69-5 N-crotonoylpiperidine 
• 74189-56-3 4-(tetrahydropyran-2-yloxy)benzaldehyde 
• 123-08-0 4-hydroxy-benzaldehyde 
• 50838-22-7 1-crotonoylpiperidine 
• 76743-25-4 (E)-4-bromo-1-(piperidin-1-yl)but-2-en-1-one 
• 597549-91-2 5-(4-methoxymethoxyphenyl)-2E,4E-butadienoic acid 
• 597549-90-1 methyl 5-(4-methoxymethoxyphenyl)-2E,4E-butadienoate 
• 6515-21-5 4-methoxymethoxy-benzaldehyde 
• 597549-92-3 N-5-(4-methoxymethoxyphenyl)-2E,4E-butadienoylpiperidine 
• 76733-92-1 N-5-(4-benzyloxyphenyl)-2E,4E-pentadienoyl piperidine 

Relevant academic research and scientific papers

Quorum sensing and nf-κb inhibition of synthetic coumaperine derivatives from piper nigrum

Bacterial communication, termed Quorum Sensing (QS), is a promising target for virulence attenuation and the treatment of bacterial infections. Infections cause inflammation, a process regulated by a number of cellular factors, including the transcription Nuclear Factor kappa B (NF-κB); this factor is found to be upregulated in many inflammatory diseases, including those induced by bacterial infection. In this study, we tested 32 synthetic derivatives of coumaperine (CP), a known natural compound found in pepper (Piper nigrum), for Quorum Sensing Inhibition (QSI) and NF-κB inhibitory activities. Of the compounds tested, seven were found to have high QSI activity, three inhibited bacterial growth and five inhibited NF-κB. In addition, some of the CP compounds were active in more than one test. For example, compounds CP-286, CP-215 and CP-158 were not cytotoxic, inhibited NF-κB activation and QS but did not show antibacterial activity. CP-154 inhibited QS, decreased NF-κB activation and inhibited bacterial growth. Our results indicate that these synthetic molecules may provide a basis for further development of novel therapeutic agents against bacterial infections.

Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/keap1 pathway

Parkinson's disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson's disease treatment.

Piperine derivative as well as preparation method and application thereof

The invention provides a piperine derivative as well as a preparation method and an application thereof. The piperine derivative is a compound shown as a formula (I), or a salt thereof, or a stereoisomer thereof, or a hydrate thereof. The compound provided by the invention can effectively protect nerve cells and improve the survival rate of the nerve cells, so that the compound provided by the invention can effectively treat neurodegenerative diseases and can be used for preparing medicines for treating the neurodegenerative diseases.

Design, synthesis and identification of novel coumaperine derivatives for inhibition of human 5-LOX: Antioxidant, pseudoperoxidase and docking studies

5-Lipoxygenase (5-LOX) is a key enzyme involved in the biosynthesis of pro-inflammatory leukotrienes, leading to asthma. Developing potent 5-LOX inhibitors especially, natural product based ones, are highly attractive. Coumaperine, a natural product found in white pepper and its derivatives were herein developed as 5-LOX inhibitors. We have synthesized twenty four derivatives, characterized and evaluated their 5-LOX inhibition potential. Coumaperine derivatives substituted with multiple hydroxy and multiple methoxy groups exhibited best 5-LOX inhibition. CP-209, a catechol type dihydroxyl derivative and CP-262-F2, a vicinal trihydroxyl derivative exhibited, 82.7% and 82.5% inhibition of 5-LOX respectively at 20 μM. Their IC50 values are 2.1 ± 0.2 μM and 2.3 ± 0.2 μM respectively, and are comparable to zileuton, IC50 = 1.4 ± 0.2 μM. CP-155, a methylenedioxy derivative (a natural product) and CP-194, a 2,4,6-trimethoxy derivative showed 76.0% and 77.1% inhibition of 5-LOX respectively at 20 μM. Antioxidant study revealed that CP-209 and 262-F2 (at 20 μM) scavenged DPPH radical by 76.8% and 71.3% respectively. On the other hand, CP-155 and 194 showed very poor DPPH radical scavenging activity. Pseudo peroxidase assay confirmed that the mode of action of CP-209 and 262-F2 were by redox process, similar to zileuton, affecting the oxidation state of the metal ion in the enzyme. On the contrary, CP-155 and 194 probably act through some other mechanism which does not involve the disruption of the oxidation state of the metal in the enzyme. Molecular docking of CP-155 and 194 to the active site of 5-LOX and binding energy calculation suggested that they are non-competitive inhibitors. The In-Silico ADME/TOX analysis shows the active compounds (CP-155, 194, 209 and 262-F2) are with good drug likeliness and reduced toxicity compared to existing drug. These studies indicate that there is a great potential for coumaperine derivatives to be developed as anti-inflammatory drug.

Synthesis of coumaperine derivatives: Their NF-κB inhibitory effect, inhibition of cell migration and their cytotoxic activity

Coumaperine (an amide alkaloid, present in white piper) and its derivatives were synthesized and investigated for their cytotoxicity against L428 and A549 cells and their NF-κB inhibitory activity. It was found that the coumaperine derivatives CP-9 and CP-38 suppress NF-κB subunits p50 and p65 in nuclear fractions by western blot and by NF-κB luciferase reporter gene assay in a dose dependent manner. Confirmation of these results was obtained by confocal microscopy. CP-9, CP-32 and CP-38 also exhibited dose dependent cell cytotoxicity in a L428?cells expressing constitutively active NF-κB and in A549?cells, with an IC50 value of 43.25?μg/ml, 0.39?μg/ml and 16.85?μg/ml respectively against L428?cells and 57.15?μg/ml, 69.1?μg/ml and 63.2?μg/ml respectively against A549?cells. In addition, the coumaperine derivatives show remarkable inhibitory activity on the cancer cell migration assay against A549 lung adenocarcinoma cells at the concentrations of 5?μg/ml, 10?μg/ml, and 5?μg/ml of CP-9, CP-32 and CP-38 respectively. Aromatic substituents and number of olefinic double bond in coumaperine derivatives found to influence the inhibitory activity. In luciferase reporter gene assay, di-olefin conjugated coumaperine derivatives, CP-38, CP-32 and PIP exhibited higher inhibitory activity than their corresponding tri-olefin conjugated coumaperine derivatives, CP-102, CP-146 and PIP-155 respectively. CP-32 with a stronger electron donating group (-N(CH3)2) showed better inhibitory activity in luciferase reporter gene assay and in cell proliferation of L428?cells. Simple coumaperine derivative (CP-9, with no substituent) effectively inhibited A549?cells proliferation and migration than the other coumaperine derivatives. CP-9 and CP-38 diminish significantly the NF-κB subunits (p50 and p65) of L428?cells in nuclear fractions at the dosage of 10?μg/ml and 30?μg/ml respectively. Which clearly shows that CP-9 and CP-38 inactivate the NF-κB pathway in?vitro.

Peroxisome Proliferator-Activated Receptor Ligand

An object of the present invention is to provide a peroxisome proliferator-activated receptor γ (PPARγ) ligand derived from a natural product and to provide a composition for prevention or improvement of insulin resistant syndrome, diabetes mellitus, obes

Novel and efficient method for esterification, amidation between carboxylic acids and equimolar amounts of alcohols, and amines utilizing Me2NSO2Cl and N,N-dimethylamines; Its application to the synthesis of coumaperine, a natural chemopreventive dieneamide

Various carboxylic esters or amides were prepared in good to excellent yield between carboxylic acids and equimolar amounts of alcohols or amines under very mild conditions (0-45°C; within 3 h) using dimethylsulfamoyl chloride (Me2NSO2Cl; 1) combined with N,N-dimethylamines (Me2NR: 2a; R=Me, 2b; R=Bu). The choice of the sulfamoyl chloride and the amine is crucial for the reaction; that is, sterically uncrowded amines accelerated the present esterification and amidation. This agent had some advantages over methanesulfonyl chloride (3)/amines as for the atom-economy, avoidance of side reactions, and had very high chemoselectivity toward the carboxyl group vs the hydroxyl group; the experiment was performed by the addition of 1 to the mixture of carboxylic acids and alcohols. Application of this method to the synthesis of coumaperine, a chemopreventive natural product, was performed using the present amidation as a key step.

Structures and Syntheses of Two Phenolic Amides from Piper nigrum L.

Two phenolic amides were isolated from the fruits of white pepper (Piper nigrum L.) and identified to be N-trans-feruloyl tyramine (2a) and N-5-(4-hydroxyphenyl)-2E,4E-pentadienoyl piperidine (6a) on the basis of chemical and spectral evidence.Both compounds were synthesized.