3822-28-4

Upstream product

• 446-52-6 2-Fluorobenzaldehyde 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 20912-79-2 4-methoxyphenacylidene dimethylsulphurane 
• 90555-36-5 N′-(2-fluorobenzylidene)-4-methylbenzenesulfonohydrazide 

Downstream Products

• 1403750-54-8 (2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(2-fluorophenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)methanone 
• 1403750-39-9 (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)(5-(2-fluorophenyl)-3-(4-methoxybenzyl)-4,5-dihydro-1H-pyrazol-1-yl)methanone 
• 610277-61-7 C₁₆H₁₅FN₂O 

Relevant academic research and scientific papers

Alkene Synthesis by Photo-Wolff-Kischner Reaction of Sulfur Ylides and N-Tosylhydrazones

A visible-light-driven and room temperature photo-Wolff-Kischner reaction of sulfur ylides and N-tosylhydrazones has been developed for the first time to provide modular access to alkene synthesis. The high functional group tolerance and broad substrate scope were demonstrated by more than 60 examples. Both E- and Z-olefinic stereochemistry in the products could be controlled with excellent stereoselectivity. A series of mechanistic studies support that the reaction should proceed through a radical-carbanion crossover pathway, specifically involving addition of photo-generated sulfur ylide radical cations to N-tosylhydrazones to form carbanions and subsequent Wolff-Kischner process.

Design, synthesis and antiproliferative activity evaluation of fluorine-containing chalcone derivatives

A series of new chalcones containing fluoro atom at B ring have been designed, synthesized, and evaluated to be antiproliferative activity against a panel of human tumor cell lines. Some of the analogs (8, 9, 12, 45, 46 and 48) displayed powerful antiproliferative effects to certain human tumor cells, but all of them were devoid of any cytotoxicity towards the normal HEK 293. Acridine orange staining data supported that the cytotoxic and antiproliferative effects of the synthesized analogs on tumor cells are mediated through apoptosis. The compounds 12 and 46 manifested concentration-dependent antiproliferative activity in human hepatocellular carcinoma cell lines using an xCELLigence assay. The structures and antiproliferative activity relationship were further supported by in silico molecular docking study of the compounds against tubulin protein which suggests our compounds interference to cell division. Communicated by Ramaswamy H. Sarma.

4-Fluoro-3′,4′,5′-trimethoxychalcone as a new anti-invasive agent. From discovery to initial validation in an in vivo metastasis model

Invasion and metastasis are responsible for 90% of cancer-related mortality. Herein, we report on our quest for novel, clinically relevant inhibitors of local invasion, based on a broad screen of natural products in a phenotypic assay. Starting from micromolar chalcone hits, a predictive QSAR model for diaryl propenones was developed, and synthetic analogues with a 100-fold increase in potency were obtained. Two nanomolar hits underwent efficacy validation and eADMET profiling; one compound was shown to increase the survival time in an artificial metastasis model in nude mice. Although the molecular mechanism(s) by which these substances mediate efficacy remain(s) unrevealed, we were able to eliminate the major targets commonly associated with antineoplastic chalcones.

Development of fluorinated methoxylated chalcones as selective monoamine oxidase-B inhibitors: Synthesis, biochemistry and molecular docking studies

A series of methoxylated chalcones with fluoro and trifluoromethyl derivatives were synthesized and investigated for their ability to inhibit human monoamine oxidase A and B. The chemical structures of the compounds have been characterized by means of the

Synthesis of a series of unsaturated ketone derivatives as selective and reversible monoamine oxidase inhibitors

We have synthesized three categories of α,β-unsaturated carbonyl derivatives and evaluated their MAO-A and MAO-B inhibitory activities. Among them, compound 10b including α,β-unsaturated ketone group showed the most potent and selective MAO-B inhibitory activity (IC50 human MAO-B 16 nM, >6000-fold selective vs MAO-A) and compound 10b exhibited good reversibility compared with selegiline, a well-known irreversible MAO-B inhibitor. However, both α,β-unsaturated amide and ester derivatives exhibited weaker MAO-B inhibition potencies. The docking studies provided insights into the possible binding modes and the key interaction sites of the synthesized MAO-B inhibitors.

Synthesis and crystal structure of chalcones as well as on cytotoxicity and antibacterial properties

A series of chalcones derivatives were synthesized and evaluated for cytotoxic and antibacterial activities in vitro. These modifications changed their bioactivity profile and indicated a combination of SAR analysis toward the substituents in rings A and

Design, modification and 3D QSAR studies of novel 2,3-dihydrobenzo[b][1,4] dioxin-containing 4,5-dihydro-1H-pyrazole derivatives as inhibitors of B-Raf kinase

Two series of novel 2,3-dihydrobenzo[b][1,4]dioxin-containing 4,5-dihydro-1H-pyrazole derivatives C1-C15 and D1-D15 have been synthesized and evaluated for their B-Raf inhibitory and anti-proliferation activities. Compound C14 ((3-(4-bromophenyl)-5-(2-fluorophenyl)-4,5-dihydro-1H-pyrazol-1-yl)(2,3- dihydrobenzo[b][1,4]dioxin-6-yl)methanone) showed the most potent biological activity against B-RafV600E (IC50 = 0.11 μM) and WM266.4 human melanoma cell line (GI50 = 0.58 μM), being comparable with the positive control Erlotinib and more potent than our previous best compound, while D10 ((2,3-dihydrobenzo[b][1,4]dioxin-2-yl)(5-(3- fluorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)methanone) performed the best in the D series (IC50 = 1.70 μM; GI50 = 1.45 μM). The docking simulation was performed to analyze the probable binding models and poses and the QSAR model was built for reasonable design of B-Raf inhibitors in future. The introduction of 2,3-dihydrobenzo[b][1,4]dioxin structure reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity.

Evaluation and discovery of novel synthetic chalcone derivatives as anti-inflammatory agents

Major anti-inflammatory agents, steroids and cyclooxygenase, were proved to have serious side effects. Here, a series of chalcone derivatives were synthesized and screened for anti-inflammatory activities. QSAR study revealed that the presence of electron-withdrawing groups in B-ring and electron-donating groups in A-ring of chalcones was important for inhibition of LPS-induced IL-6 expression. Further, compounds 22, 23, 26, 40, and 47 inhibited TNF-α and IL-6 release in a dose-dependent manner and decreased LPS-induced TNF-α, IL-1β, IL-6, IL-12, and COX-2 mRNA production. Mechanistically, compounds 23 and 26 interfered with JNK/NF-κB signaling and dose-dependently prevented ERK and p38 activation. In addition, 23 and 26 exhibited a significant protection against LPS-induced death and were able to block high glucose-activated cytokine profiles in macrophages. Together, these data show a series of anti-inflammatory chalcones with potential therapeutic effects in inflammatory diseases.

Solution-phase parallel synthesis of substituted chalcones and their antiparasitary activity against Giardia lamblia

A library of 25-membered chalcones was prepared by parallel synthesis. Substituted acetophenones and benzaldehydes were condensed using the Claisen-Schmidt base-catalyzed aldol condensation. Several chalcones showed in vitro antiparasitic activity against Giardia lamblia. The highest activity observed for the IC50 values were 12.72, 15.05 and 15.31 μg/mL, respectively; these are potential leads for the development of antigiardial compounds.

Discovery of fluorescent cyanopyridine and deazalumazine dyes using small molecule macroarrays

Small molecule macroarrays of cyanopyridines and deazalumazines were generated in high purities via spatially addressed synthesis on planar cellulose supports. Examination of the spectral properties of the heterocycles both on and off of the planar suppor