342808-40-6

Usage

Uses

Used in Pharmaceutical Industry:
3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone is used as a kinase inhibitor for its anticancer properties. 3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone targets specific kinases involved in cell signaling pathways that regulate cell growth, proliferation, and survival, thereby exhibiting potential therapeutic effects against various types of cancer. Its ability to inhibit these kinases can lead to the suppression of tumor growth and the prevention of cancer progression.
Additionally, 3,5-Bis[(2-fluorophenyl)Methylene]-4-piperidinone may be employed in combination therapies, where it can enhance the efficacy of existing chemotherapeutic agents or targeted therapies. This can be particularly beneficial in cases of drug resistance or when conventional treatments have limited effectiveness.

Upstream product

• 342808-24-6 3,5-bis(2-pyridinylmethylidene)-4-piperidone 
• 1217237-15-4 3,5-bis(2-fluorobenzylidene)-4-piperidone hydrochloride 
• 41979-39-9 4-piperidone hydrochloride 
• 446-52-6 2-Fluorobenzaldehyde 
• 41661-47-6 piperidin-4-one 
• 342808-41-7 3,5-bis-(2-fluorobenzylidene)-4-piperidone acetic acid 

Downstream Products

• 600637-08-9 4-[3,5-bis(2-fluorobenzylidene)-4-oxo-piperidin-1-yl]-4-oxo-butanoic acid 
• 896743-51-4 5-[3,5-bis-(2-fluorobenzylidene)-4-oxopiperidin-1-yl]-5-oxopentanoic acid 
• 1246964-13-5 3,5-bis(2-fluorobenzyl)-4-piperidone 
• 939343-12-1 N-acetyl-3,5-bis(2-fluorobenzylidene)-4-piperidone 
• 1437707-98-6 C₂₀H₁₇F₂N₃O 

Relevant academic research and scientific papers

Anti-inflammatory activity of ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives in vitro and in vivo

Curcumin was reported as an anti-inflammatory agent. However, curcumin's poor bioavailability limited its clinical utility. Here, thirty ortho-substituted mono-carbonyl curcumin derivatives, containing acetone, cyclopentanone, cyclohexanone or 4-piperidione (N—H, N-methyl or N-acrylyl) moieties replacing β-diketone moiety of curcumin, were investigated for anti-inflammatory activity. Two active ortho-trifluoromethoxy-substituted 4-piperidione-containing derivatives 22 and 24 owned good cell uptake ability, and displayed excellent anti-inflammatory activity in both lipopolysaccharide-induced Raw264.7 macrophages and a dextran sulfate sodium (DSS)-induced mouse model of colitis. They inhibited the production of nitric oxide, reactive oxygen species, malonic dialdehyde and cyclooxygenase-2; and the expression of pro-inflammatory cytokines interleukin-1β, tumor necrosis factor-α and myeloperoxidase; the phosphorylation of mitogen-activated protein kinases; and the nucleus translocation of p65. What's more, 22 or 24 oral administered reduced the severity of clinical symptoms of ulcerative colitis (body weight and disease activity index), and reduced obviously DSS-induced colonic pathological damage (the colon length and histopathology analysis). These results suggested that ortho-trifluoromethoxy-substituted 4-piperidione-containing mono-carbonyl curcumin derivatives 22 and 24 were potential anti-inflammatory agents; and offered the important information for design and discovery of more potent anti-inflammatory drug candidates.

Spirooxindole-pyrrolothiazole heterocyclic hybrids

The spirooxindole-pyrrolothiazole heterocyclic hybrids are compounds having the formula: wherein R is hydrogen and R′ is fluorine (compound 6a) or R is fluorine and R′ is hydrogen (compound 6b). The hybrids may be obtained using a chemical synthesis process involving 1,3-dipolar cycloaddition of 3,5-bis(4/2-fluoro-benzylidene) piperidin-4-ones with isatin and 4-thiazolidinecarboxylic acid in a suitable solvent, preferably 1-butyl-3-methyl-imidazolium bromide (“[bmim]Br”), and preferably under microwave irradiation. Both of these new hybrids demonstrate antimicrobial activity against both gram positive and gram negative drug resistant and non-resistant bacterial pathogens, although compound 6a exhibits more potent antibacterial activity than compound 6b.

3,5-Bis(2-fluorobenzylidene)-4-piperidone induce reactive oxygen species-mediated apoptosis in A549 cells

The presence of the substituents in the ortho position of the aromatic ring(s) is helpful to strenghen the biological activity, highlighting a so-called ortho effect. In this paper, we synthesized six mono-carbonyl curcumin analogs with the fluorine group

Design, synthesis, and antiproliferative activity assessment of non-ATP-competitive fibroblast growth factor receptor 1 inhibitors

Fibroblast growth factor receptor 1 (FGFR1) is considered a therapeutic target for multiple cancers, including gastric cancer. FGFR1 inhibitors, being ATP competitors, can prevent the kinase domain and the downstream signaling cascade from phosphorylation

Synthesis and discovery of highly functionalized mono- and bis-spiro-pyrrolidines as potent cholinesterase enzyme inhibitors

Novel mono and bis spiropyrrolidine derivatives were synthesized via an efficient ionic liquid mediated, 1,3-dipolar cycloaddition methodology and evaluated in vitro for their AChE and BChE inhibitory activities in search for potent cholinesterase enzyme

Microwave assisted synthesis, cholinesterase enzymes inhibitory activities and molecular docking studies of new pyridopyrimidine derivatives

A series of hitherto unreported pyrido-pyrimidine-2-ones/pyrimidine-2- thiones were synthesized under microwave assisted solvent free reaction conditions in excellent yields and evaluated in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes inhibitory activity. Among the pyridopyrimidine derivatives, 7e and 7l displayed 2.5- and 1.5-fold higher enzyme inhibitory activities against AChE as compared to standard drug, galanthamine, with IC50 of 0.80 and 1.37 μM, respectively. Interestingly, all the compounds except 6k, 7j and 7k displayed higher inhibitory potential against BChE enzyme in comparison to standard with IC50 ranging from 1.18 to 18.90 μM. Molecular modeling simulations of 7e and 7l was performed using three-dimensional structure of Torpedo californica AChE (TcAChE) and human butyrylcholinesterase (hBChE) enzymes to disclose binding interaction and orientation of these molecule into the active site gorge of respective receptors.

Anticancer Activity of an Imageable Curcuminoid 1-[2-Aminoethyl-(6-hydrazinopyridine-3-carbamidyl)-3,5-bis-(2-fluorobenzylidene)-4-piperidone (EFAH)

3,5-Bis(2-fluorobenzylidine)-4-piperidone or EF24 is a potent anticancer derivative of curcumin. Using an amine derivative of EF24, we synthesized a hydrazinonicotinic acid conjugate, EFAH, for Tc-99m radiolabelling and single photon emission tomography imaging. The aqueous solubility of EFAH (3.5mg/mL) was significantly more than that of EF24 (1.2mg/mL); the octanol/water partition coefficient of EFAH was estimated at log P=0.33. As an antiproliferative agent, EFAH was as effective as EF24 in suppressing the proliferation of H441, MiaPaCa-2 and Panc-1 cells. Daily intraperitoneal injection of EFAH (5μg) for 3weeks in mice carrying xenografts of Panc-1 pancreatic cancer showed a mean tumour volume reduction of 79%; the tumour weight decreased by 82% in the treated group. For imaging and biodistribution, EFAH was labelled with Tc-99m (98% RCY) and intravenously administered in rats. Approximately 23.7% and 14.3% of injected dose accumulated in liver and intestine, respectively, suggesting that EFAH is mostly eliminated by hepatobiliary route. The results indicate that HYNIC modification of EF24 for Tc-99m radiolabelling does not affect its antiproliferative efficacy. For the first time, a visual biodisposition of EF24 in a live animal model has been demonstrated. Such knowledge could be of benefit in developing therapeutic curcuminoids, such as EF24.

CLEFMA - An anti-proliferative curcuminoid from structure-activity relationship studies on 3,5-bis(benzylidene)-4-piperidones

3,5-Bis(benzylidene)-4-piperidones are being advanced as synthetic analogs of curcumin for anti-cancer and anti-inflammatory properties. We performed structure-activity relationship studies, by testing several synthesized 3,5-bis(benzylidene)-4-piperidones for anti-proliferative activity in lung adenocarcinoma H441 cells. Compared to the lead compound 1, or 3,5-bis(2-fluorobenzylidene)-4-piperidone, five compounds were found to be more potent (IC50 50 >50 μM). Based on the observations, we synthesized 4-[3,5-bis(2-chlorobenzylidene-4-oxo-piperidine-1-yl)-4-oxo-2- butenoic acid] (29 or CLEFMA) as a novel analog of 1. CLEFMA was evaluated for anti-proliferative activity in H441 cells, and was found to be several folds more potent than compound 1. We did not find apoptotic cell population in flow cytometry, and the absence of apoptosis was confirmed by the lack of caspase cleavage. The electron microscopy of H441cells indicated that CLEFMA and compound 1 induce autophagic cell death that was inhibited by specific autophagy inhibitor 3-methyladenine. The results suggest that the potent and novel curcuminoid, CLEFMA, offers an alternative mode of cell death in apoptosis-resistant cancers.

Curcumin analog cytotoxicity against breast cancer cells: exploitation of a redox-dependent mechanism

A series of novel curcumin analogs, symmetrical dienones, were previously shown to possess cytotoxic, anti-angiogenic and anti-tumor activities. Analogs 1 (EF24) and 2 (EF31) share the dienone scaffold and serve as Michael acceptors. We propose that the anti-cancer effects of 1 and 2 are mediated in part by redox-mediated induction of apoptosis. In order to support this concept, 1 and 2 were treated with l-glutathione (GSH) and cysteine-containing dipeptides under mild conditions to form colorless water-soluble adducts, which were identified by LC/MS. Comparison of the cytotoxic action of 1, 2 and the corresponding conjugates, 1-(GSH)2 and 2-(GSH)2, illustrated that the two classes of compounds exhibit essentially identical cell killing capabilities. Compared with the yellow, somewhat light sensitive and nearly water insoluble compounds 1 and 2, the glutathione conjugates represent a promising new series of stable and soluble anti-tumor pro-drugs.