330450-40-3

Upstream product

• 459-57-4 4-fluorobenzaldehyde 
• 41979-39-9 4-piperidone hydrochloride 
• 1379669-18-7 3,5-bis(4-fluorobenzylidene)piperidin-4-one hydrochloride 
• 41661-47-6 piperidin-4-one 

Downstream Products

• 330450-44-7 C₂₂H₁₇F₂NO₂ 

Relevant academic research and scientific papers

Synthesis, human topoisomerase IIα inhibitory properties and molecular modeling studies of anti-proliferative curcumin mimics

3,5-Bis(arylidene)-N-substituted-4-oxo-piperidine-1-carboxamides 24-51 were synthesized as curcumin mimics in a facile pathway through reaction of 3,5-bis(arylidene)-4-piperidones with the appropriate isocyanate in the presence of triethylamine. The 3E,5E′-stereochemical configuration was conclusively supported by single crystal X-ray studies of compounds 25 and 34. Most of the synthesized piperidinecarboxamides showed high anti-proliferative properties with potency higher than that of 5-fluorouracil (clinically approved drug against colon, breast and skin cancers) through in vitro MTT bio-assay. Some of them revealed anti-proliferative properties at sub-micromolar values (IC50 = 0.56-0.70 μM for compounds 29, 30 and 34-38 against HCT116; and IC50 = 0.64 μM for compound 30 against A431 cell lines) with promising inhibitory properties against human DNA topoisomerase IIα. The safe profile of the anti-proliferative active agents against the RPE1 normal cell line may prove their selectivity towards carcinoma cells. Robust molecular models (2D-QSAR, 3D-pharmacophore) supported the SAR and validated the observed bio-properties.

Synthesis, biological evaluation and molecular docking studies against EGFR tyrosine kinase of 3,5-bis(Substituted benzylidene)-1-ethylpiperidin-4-one analogues

Cancer is one of the leading causes of death. The aim of the present study was to syn-thesize and investigate the anticancer and antioxidant activities of some 3,5-bis(substituted benzyl-idene)-1-ethylpiperidin-4-one analogues (4a-g). The 3,5-bis(substituted benzylidene)-1-ethylpiperidin-4-one analogues (4a-g) were prepared from the precursor, piperidin-4-one hydrochloride (1). The initial step involved the synthesis of inter-mediates, 3,5-bis(substituted benzylidene)piperidin-4-one analogues (3a-g) followed by their eth-ylation with C2H5I in acetone and K2CO3 to obtain the title compounds (4a-g). The Fourier trans-form infrared (FTIR), nuclear magnetic resonance (1H &13C NMR), mass spectrometry and mi-croanalysis were used to characterize the title compounds (4a-g). All the compounds were further evaluated for their anticancer activity by SRB assay and NCI US protocol, while the antioxidant activity was evaluated by DPPH free radical assay. All the title compounds (4a-g) were subjected to molecular docking studies against EGRF tyrosine kinase, a potential target for anticancer agents, to study the possible mode of interaction of our compounds with the molecular target. The compound 4g showed significant anticancer activity with GI50 of 28.2 μM against MCF-7 (Breast cancer cell line). The antioxidant activity of compound 4g (IC50 = 14.98±0.91 μM) was found to be comparable to the standard drug ascorbic acid. The binding modes of compounds 4a-g against the molecular target EGFR tyrosine kinase were also studied. The structure-activity rela-tionship (SAR) was also studied. The compound 4g showed significant anticancer activity with GI50 of 28.2 μM against MCF-7 (Breast cancer cell line). The antioxidant activity of the compound, 4g was found to be comparable to the standard drug ascorbic acid, while its anticancer activity was found to be less than that of the standard drug adriamycin.

A one-pot three-component synthesis and investigation of the in vitro mechanistic anticancer activity of highly functionalized spirooxindole-pyrrolidine heterocyclic hybrids

With an aim to develop more effective and affordable anticancer agents possessing a unique mechanism of action, we designed and synthesized derivatives of spirooxindole-pyrrolidine heterocyclic hybrids in good yields through a one-pot three-component (3+2) cycloaddition strategy. The synthesized compounds were characterized thoroughly for the physicochemical properties by making use of FT-IR, NMR spectroscopy, and mass spectrometry. Further, these compounds have been evaluated for the influence of anticancer activity against HepG2 cells up to 200 μg/mL concentration. The highly active molecular scaffold was tested for the in-depth mechanistic studies, and it was found that the major pathway of cell death is apoptosis which occurs through the induction of reactive oxygen species followed by the involvement of caspases.

Design, synthesis, and biological evaluation of novel EF24 and EF31 analogs as potential IκB kinase β inhibitors for the treatment of pancreatic cancer

Given the important role that inhibitory kappa B (IκB) kinase β (IKKβ) plays in pancreatic cancer (PC) development and progression, inhibitors targeting IKKβ are believed to be increasingly popular as novel anti-PC therapies. Two synthetic molecules, named EF24 and EF31, exhibited favorable potential in terms of inhibition of both IKKβ activity and PC cell proliferation. Aiming to enhance their cellular efficacy and to analyze their structure-activity relationship, four series of EF24 and EF31 analogs were designed and synthesized. Through kinase activity and vitality screening of cancer cells, D6 displayed excellent inhibition of both IKKβ activity and PC cell proliferation. Additionally, multiple biological evaluations showed that D6 was directly bound to IKKβ and significantly suppressed the activation of the IKKβ/nuclear factor κB pathway induced by tumor necrosis factor-α, as well as effectively inducing cancer cell apoptosis. Moreover, molecular docking and molecular dynamics simulation analysis indicated that the dominant force between D6 and IKKβ comprised hydrophobic interactions. In conclusion, D6 may be a promising therapeutic agent for PC treatment and it also provides a structural lead for the design of novel IKKβ inhibitors.

Tumour-specific cytotoxicity and structure-activity relationships of novel 1-[3-(2-methoxyethylthio)propionyl]-3,5-bis(benzylidene)-4-piperidones

A series of 1-acyl-3,5-bis(benzylidene)-4-piperidones 3-7 were designed and synthesized as novel cytotoxic agents. These compounds displayed potent cytotoxic properties towards human Molt4/C8, CEM, HSC-2, HSC-3 and HSC-4 neoplasms and also to murine L1210

Curcumin borate derivatives and their preparation method and use

The invention relates to compounds shown in the general formula (I) or their pharmaceutically acceptable salts or solvates and also relates to a preparation method of the compounds and a use of the compounds in preparation of drugs as 19S proteasome inhibitors.

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.

Novel 3,5-bis(arylidene)-4-piperidone dimers: Potent cytotoxins against colon cancer cells

Two novel series of dimeric 3,5-bis(arylidene)-4-piperidones 7 and 8 were prepared as cytotoxic agents. A specific objective of this study was the discovery of novel compounds displaying potent anti-proliferative activities against colon cancers. Most of

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.