214783-17-2

Upstream product

• 495-76-1 piperonol 
• 7664-93-9 sulfuric acid 
• 1026651-89-7 (1,3-benzodioxol-5-yl)methyl 4-methylbenzenesulfonate 
• 2606-51-1 3,4-Methylenedioxybenzyl bromide 
• 20850-43-5 5-(chloromethyl)-1,3-benzodioxole 
• 2620-50-0 1,3-benzodioxol-5-ylmethyl amine 
• 78358-16-4 1,3-benzodioxol-5-ylmethyl methanesulfonate 

Downstream Products

• 68291-93-0 N-[3,4-(methylenedioxy)benzyl]propylamine 
• 1227780-03-1 1-(2-((1-(benzo[d][1,3]dioxol-5-ylmethyl)-1H-1,2,3-triazol-4-yl)methylamino)-6-(3,5-dimethoxyphenyl)pyrido[2,3-d]pyrimidin-7-yl)-3-tert-butylurea 
• 4421-09-4 piperonylonitrile 
• 120-57-0 piperonal 
• 2620-50-0 1,3-benzodioxol-5-ylmethyl amine 
• 15205-27-3 N-methylpiperonylamine 
• 58995-64-5 1-(N,N-dimethylaminomethyl)-3,4-(methylenedioxy)benzene 
• 2620-49-7 3,4-methylenedioxybenzylamine hydrochloride 

Relevant academic research and scientific papers

The development of a versatile trifunctional scaffold for biological applications

We describe the synthesis of a trifunctional scaffold constructed from a planar core of trimesic acid derivatized with three propargylamine moieties. The scaffold was attached to a solid-phase resin through the carboxylic group of a fluorinated alkyl spacer arm. The orthogonal protection of two of the alkyne groups with triethylsilyl and triisopropylsilyl moieties enabled modular and efficient derivatization of the scaffold with three different azides by using solid-phase synthesis on amphiphilic ChemMatrix resin. We showed that a fluorine label can be used to quantify the content of fluorine-containing compounds by 19F NMR spectroscopic analysis after cleavage from the resin. We have thus designed a versatile and convenient tool that could be useful for simple and rapid solid-phase syntheses of combinatorial libraries of the scaffold-based compounds, for example as new protein binders. The development of a trifunctional scaffold derivatized with three orthogonally protected alkyne moieties that is useful for the solid-phase synthesis of combinatorial libraries is described.

ROMP copolymers for orthogonal click functionalizations

The ring-opening metathesis polymerization using ruthenium carbene initiators developed by Grubbs et al. is one of the most functional group tolerant living polymerization methods known. One of the most used postpolymerization functionalization methods used today is the copper-catalyzed 1,3-dipolar cycloaddition between alkynes and organic azides. Organic azides are, however, not tolerated by ruthenium carbene initiators, and nonprotected alkynes have been shown to slow down the propagation reaction or react with the propagating species leading to broad molecular weight distributions. Here we report the copolymer synthesis of three orthogonally functionalizable monomers: one carrying an activated pentafluorophenyl ester, one a maleimide unit, and a third one a trialkylsilyl-protected alkyne. From these monomers, statistical terpolymers as well as diblock copolymers were synthesized with different molecular weights and monomer compositions or block ratios, respectively. Excellent control over molecular weight and molecular weight distribution could be achieved using Grubbs' first-generation ruthenium carbene initiator. Herein we present the synthesis and orthogonal triple postpolymerization functionalization of these copolymers.

Synthesis of 1,2,3-triazole benzophenone derivatives and evaluation of in vitro sun protection, antioxidant properties, and antiproliferative activity on HT-144 melanoma cells

Benzophenones display several biological activities, including antioxidant, anticancer, and photoprotective. Furthermore, antioxidants can minimize both ultraviolet absorption and tumor development. In the present investigation, a series of twenty-six 1,2

Synthesis of 1,2,3-triazole derivatives of hydnocarpic acid isolated from carpotroche brasiliensis seed oil and evaluation of antiproliferative activity

Carpotroche brasiliensis is a tree native to Brazil, belonging to the family Flacurtiaceae, whose seeds contain a group of cyclopentenyl fatty acids: Gorlic (12%), chaulmugric (27%), and hydnocarpic (48.7%). These compounds are considered the main therapeutic agents in the treatment of leprosy. In the present study, a series of novel triazole compounds were obtained by conjugation between hydnocarpic acid and functionalized azides via copper(I)-catalyzed azidealkyne cycloaddition reaction (CuAAC). Hydnocarpic acid and its derivatives were tested against estrogen-positive breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and non-small cell lung cancer (A549) cell lines. The (R)-(1-(pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl-11-(cyclopent-2-en-1-yl)undecanoate (8) displayed promising antiproliferative activity against A549 cells. We demonstrated that this compound selectively inhibited the viability of A549 cell cultures. Furthermore, compound 8 inhibited the clonogenic capacity of A549 cells, and this effect was associated to its ability to inhibit cell cycle progression at G1 phase. These findings indicate that 8 is a promising antitumor agent on A549 cells and support further studies to evaluate the molecular mechanisms underlying its antiproliferative activity. In addition, hydnocarpic acid should be considered as a promising chemical prototype to obtain novel antineoplastic agents.

A caffeic acid-ferulic acid hybrid compound attenuates lipopolysaccharide-mediated inflammation in BV2 and RAW264.7 cells

In the present study, we synthesized and evaluated the anti-inflammatory effects of the two component hybrids, caffeic acid (CA)-ferulic acid (FA), FA-Tryptamine (Trm), CA-Piperonyl Triazol (PT) and FA-PT. Of these five hybrids, CA-FA had the most potent

Sustainable organophosphorus-catalysed Staudinger reduction

A highly efficient and sustainable catalytic Staudinger reduction for the conversion of organic azides to amines in excellent yields has been developed. The reaction displays excellent functional group tolerance to functionalities that are otherwise prone to reduction, such as sulfones, esters, amides, ketones, nitriles, alkenes, and benzyl ethers. The green nature of the reaction is exemplified by the use of PMHS, CPME, and a lack of column chromatography.

Selective synthesis of mono- and di-methylated amines using methanol and sodium azide as C1 and N1 sources

A Ru(ii) complex mediated synthesis of various N,N-dimethyl and N-monomethyl amines from organic azides using methanol as a methylating agent is reported. This methodology was successfully applied for a one-pot reaction of bromide derivatives and sodium azide in methanol. Notably, by controlling the reaction time several N-monomethylated and N,N-dimethylated amines were synthesized selectively. The practical applicability of this tandem process was revealed by preparative scale reactions with different organic azides and synthesis of an anti-vertigo drug betahistine. Several kinetic experiments and DFT studies were carried out to understand the mechanism of this transformation.

Small Molecule Microarray Based Discovery of PARP14 Inhibitors

Poly(ADP-ribose) polymerases (PARPs) are key enzymes in a variety of cellular processes. Most small-molecule PARP inhibitors developed to date have been against PARP1, and suffer from poor selectivity. PARP14 has recently emerged as a potential therapeutic target, but its inhibitor development has trailed behind. Herein, we describe a small molecule microarray-based strategy for high-throughput synthesis, screening of >1000 potential bidentate inhibitors of PARPs, and the successful discovery of a potent PARP14 inhibitor H10 with >20-fold selectivity over PARP1. Co-crystallization of the PARP14/H10 complex indicated H10 bound to both the nicotinamide and the adenine subsites. Further structure–activity relationship studies identified important binding elements in the adenine subsite. In tumor cells, H10 was able to chemically knockdown endogenous PARP14 activities.

Fused Bicyclic Caspase-1 Inhibitors Assembled by Copper-Free Strain-Promoted Alkyne–Azide Cycloaddition (SPAAC)

Challenges exist in the development of potent and selective small-molecule inhibitors against caspase-1. Herein, by making use of the copper-free strain-promoted alkyne–azide cycloaddition (SPAAC) reaction between difluorinated cyclooctynes (DIFOs) and va

Triazole substitution of a labile amide bond stabilizes pantothenamides and improves their antiplasmodial potency

The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo. In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC50s) of ～50 nM, and three others have submicromolar IC50s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [14C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase.