584-45-2

Usage

InChI:InChI=1/C10H8O4/c11-9(12)8(10(13)14)6-7-4-2-1-3-5-7/h1-6H,(H,11,12)(H,13,14)

Upstream product

• 64-17-5 ethanol 
• 141-82-2 malonic acid 
• 581-55-5 benzylidene 1,1-diacetate 
• 100-52-7 benzaldehyde 
• 64-19-7 acetic acid 
• 105-53-3 diethyl malonate 
• 92-29-5 hydrobenzamide 
• 67-56-1 methanol 
• 698-88-4 (2,2-dichlorovinyl)benzene 
• 201230-82-2 carbon monoxide 
• 705-54-4 (Z)-α-chlorocinnamic acid 
• 705-55-5 (E)-2-chloro-3-phenylacrylic acid 
• 56264-83-6 N-(α-ethoxy-benzyl)-acetanilide 
• 68687-36-5 4-Oxo-2,6-diphenyl-1-oxa-cyclohexane-3,5-ethyl dicarboxylate 

Downstream Products

• 621-82-9 Cinnamic acid 
• 473-90-5 acetonedicarboxylic acid 
• 140-10-3 (E)-3-phenylacrylic acid 
• 140-10-3 cis-cinnamic acid 
• 32046-40-5 benzylidenemalonyl dichloride 
• 538-56-7 cinnamic acid anhydride 
• 3646-50-2 3-Amino-3-phenylpropionic acid 
• 616-75-1 2-benzylmalonic acid 
• 100-52-7 benzaldehyde 
• 65-85-0 benzoic acid 
• 588-64-7 benzaldehyde phenylhydrazone 
• 7345-79-1 2-bromocinnamic acid 
• 124-38-9 carbon dioxide 
• 141-82-2 malonic acid 

Relevant academic research and scientific papers

Exploring the Promiscuous Enzymatic Activation of Unnatural Polyketide Extender Units in Vitro and in Vivo for Monensin Biosynthesis

The incorporation of new-to-nature extender units into polyketide synthesis is an important source for diversity yet is restricted by limited availability of suitably activated building blocks in vivo. We here describe a straightforward workflow for the biogenic activation of commercially available new-to-nature extender units. Firstly, the substrate scope of a highly flexible malonyl co-enzyme A synthetase from Streptomyces cinnamonensis was characterized. The results were matched by in vivo experiments in which the said extender units were accepted by both the polyketide synthase and the accessory enzymes of the monensin biosynthetic pathway. The experiments gave rise to a series of predictable monensin derivatives by the exploitation of the innate substrate promiscuity of an acyltransferase and downstream enzyme functions.

Development of the First Two-Pore Domain Potassium Channel TWIK-Related K+ Channel 1-Selective Agonist Possessing in Vivo Antinociceptive Activity

The TWIK-related K+ channel, TREK-1, has recently emerged as an attractive therapeutic target for the development of a novel class of analgesic drugs, suggesting that activation of TREK-1 could result in pain inhibition. Here, we report the synthesis of a series of substituted acrylic acids (1-54) based on our previous work with caffeate esters. The analogues were evaluated for their ability to modulate TREK-1 channel by electrophysiology and for their in vivo antinociceptive activity (acetic acid-induced writhing and hot plate assays), leading to the identification of a series of novel molecules able to activate TREK-1 and displaying potent antinociceptive activity in vivo. Furyl analogue 36 is the most promising of the series.

Indium(III)-catalyzed knoevenagel condensation of aldehydes and activated methylenes using acetic anhydride as a promoter

The combination of a catalytic amount of InCl3 and acetic anhydride remarkably promotes the Knoevenagel condensation of a variety of aldehydes and activated methylene compounds. This catalytic system accommodates aromatic aldehydes containing a variety of electron-donating and -withdrawing groups, heteroaromatic aldehydes, conjugate aldehydes, and aliphatic aldehydes. Central to successfully driving the condensation series is the formation of a geminal diacetate intermediate, which was generated in situ from an aldehyde and an acid anhydride with the assistance of an indium catalyst.

Synthesis of arylidene propanedioic acids by Knoevenagel condensation for use in ceramic sols

This paper is primarily concerned with the synthesis of arylidene propanedioic acids by Knoevenagel condensation. Generally organic bases pyridine and piperidine are used as catalyst in Knoevenagel condensation which are costly and health hazard. In this research work, Knoevenagel condensation of various aromatic aldehydes (benzaldehyde, salicylaldehyde and p-chlorobenzaldehyde) and active methylenes (malonic acid and ethyl acetoacetate) was carried out in the presence of amino acids (glycine, lysine, hippuric acid, methionine and leucine) as catalyst. Using salicylaldehyde gave coumarin-3-carboxylic acid, a solvent free synthesis. These products were isolated and purified and were characterized through melting points, TLC, IR, mass and 1H NMR. These acids are synthesized for eventual development of organically modified ceramic nano powders.

Synthesis of a new urea derivative: A dual-functional organocatalyst for Knoevenagel condensation in water

A phenylalanine-urea compound-catalyzed Knoevenagel condensation in water is reported. Various aldehydes and active methylene compounds undergo condensation at room temperature to give the desired products in high yields. The mechanism of the condensation of aldehydes with Meldrum's acid catalyzed by the novel urea derivative is also disclosed.

Identification of cinnamic acid derivatives as novel antagonists of the prokaryotic proton-gated ion channel GLIC

Pentameric ligand gated ion channels (pLGICs) mediate signal transduction. The binding of an extracellular ligand is coupled to the transmembrane channel opening. So far, all known agonists bind at the interface between subunits in a topologically conserved "orthosteric site" whose amino acid composition defines the pharmacological specificity of pLGIC subtypes. A striking exception is the bacterial proton-activated GLIC protein, exhibiting an uncommon orthosteric binding site in terms of sequence and local architecture. Among a library of Gloeobacter violaceus metabolites, we identified a series of cinnamic acid derivatives, which antagonize the GLIC proton-elicited response. Structure-activity analysis shows a key contribution of the carboxylate moiety to GLIC inhibition. Molecular docking coupled to site-directed mutagenesis support that the binding pocket is located below the classical orthosteric site. These antagonists provide new tools to modulate conformation of GLIC, currently used as a prototypic pLGIC, and opens new avenues to study the signal transduction mechanism.

Polycarbosilane-supported titanium(IV) catalyst for Knoevenagel condensation reaction

Polycarbosilane (PCS) was synthesized by the polycondensation of trichloromethylsilane and trimethoxyvinylsilane in the presence of sodium metal. PCS has a highly crosslinked structure, high ceramic yield and high surface area. Titanium metal ion was attached to the polycarbosilane and its catalytic activity was investigated. The Knoevenagel condensation reaction catalysed by titanium-incorporated polycarbosilane is reported. The titanium-incorporated PCS catalysed the reaction well and with a diverse set of substrates the reaction proceeded with good yield. PCS-supported transition metal catalysts have been prepared for the first time and used successfully in the Knoevenagel condensation reaction. Copyright

β-alanine-DBU: A highly efficient catalytic system for knoevenagel-doebner reaction under mild conditions

A mild and efficient Knoevenagel-Doebner reaction from malonic acid and a wide range of aldehydes was catalyzed by a catalytic system consisting of β-alanine and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), affording the corresponding (E)-α,β-unsaturated carboxylic acids in good to excellent yields and with high stereoselectivity. The advantage of the method is that the reaction could proceed smoothly at ambient temperature so that it can tolerate a variety of functional groups and avoid unnecessary side reactions. Copyright

Selection, synthesis, and anti-inflammatory evaluation of the arylidene malonate derivatives as TLR4 signaling inhibitors

Inhibition of TLR4 signaling is an important therapeutic strategy for intervention in the etiology of several pro-inflammatory diseases. There has been intensive research in recent years aiming to explore this strategy, and identify small molecule inhibitors of the TLR4 pathway. However, the recent failure of a number of advanced drug candidates targeting TLR4 signaling (e.g., TAK242 and Eritoran) prompted us to continue the search for novel chemical scaffolds to inhibit this critical inflammatory response pathway. Here we report the identification of a group of new TLR4 signaling inhibitors through a cell-based screening. A series of arylidene malonate analogs were synthesized and assayed in murine macrophages for their inhibitory activity against LPS-induced nitric oxide (NO) production. The lead compound 1 (NCI126224) was found to suppress LPS-induced production of nuclear factor-kappaB (NF-κB), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) in the nanomolar-low micromolar range. Taken together, this study demonstrates that 1 is a promising potential therapeutic candidate for various inflammatory diseases.

Knoevenagel condensation catalyzed by chemo-selective Ni-nanoparticles in neutral medium

Recyclable Ni-nanoparticles provides an efficient, economic and rapid method for catalyzing Knoevenagel condensation of aldehydes with an active methylene compound at room temperature. The method offers high yield preferably in case of aromatic aldehydes and proceed well in neutral medium. This method provides a wide range of substrate applicability and simple workup procedure. The products need no further purification and the process is environmentally benign.