22535-53-1

Upstream product

• 99-92-3 p-aminobenzophenone 
• 814-68-6 acryloyl chloride 
• 121-44-8 triethylamine 

Downstream Products

• 86523-82-2 N-(4-acetylphenyl)-3-<4-(2-pyridinyl)-1-piperazinyl>propanamide 
• 86523-83-3 N-<4-(1-hydroxyethyl)phenyl>-3-<4-(2-pyridinyl)-1-piperazinyl>propanamide 
• 104373-62-8 N-(4-acetylphenyl)-3-<4-(5-bromo-2-pyridinyl)-1-piperazinyl>propanamide monohydrobromide 
• 7470-51-1 propionic acid-(4-acetyl-anilide) 

Relevant academic research and scientific papers

Synthesis of 4-Trifluoromethylated 1,3-Butadienes via Palladium Catalyzed Heck Reaction

1,3-Butadiene plays a key role in modern synthetic chemistry and biochemistry because it is a key intermediate in the synthesis of many drugs. A new and effective method for the synthesis of 4-trifluoromethylated 1,3-butadiene through the fluorinated Heck reaction catalyzed by Pd(0) is described. Without additives, 1-chloro-3,3,3-trifluoropropene (an inexpensive CF3 structural unit that is harmless to ozone) reacts with enamide to synthesize 4-trifluoromethylated 1,3-butadienes with good yield, high regioselectivity and chemical selectivity, and strong tolerance of substrate functional groups such as alkynes, aldehyde, and ester groups.

Discovery of a new tetramethylpyrazine based chalcone with α, β-unsaturated ketone moiety as a potential anticancer agent

In this study, a new ligustrazine-based chalcone molecule has been synthesized that contains an extra α, β-Unsaturated ketone moiety along with α, the β-Unsaturated carbonyl group of chalone. A new tetramethylpyrazine (TMP) based aldehyde was synthesized to make the TMP (ligustrazine) as part of chalcone and then it was reacted with newly synthesized ketone containing additional α, β-Unsaturated ketone moiety. After characterization, this new compound was evaluated for its effect on different types of cancer cell lines and very promising results were obtained. The growth of these cancer cells was inhibited by newly designed and synthesized compounds, especially for colon and pancreatic cancer cells with IC50 0.04-0.05 μM.

COMPOSITONS AND METHODS FOR MODULATING UBA5

Disclosed herein, inter alia, are compositions and methods useful for inhibiting ubiquitin-like modifier activating enzyme 5.

COMPOSITIONS AND METHODS FOR MODULATING PPP2R1A

Disclosed herein, inter alia, are compositions and methods useful for modulating PPP2R1 A and for the treatment of cancer.

COMPOSITIONS AND METHODS FOR INHIBITING RETICULON 4

Disclosed herein, inter alia, are compositions and methods useful for inhibiting reticulon 4(RTN4).

Novel oxime-palladacycle supported on clay composite as an efficient heterogeneous catalyst for Sonogashira reaction

A novel supported catalyst formed by an oxime-derived palladacycle supported on clay OxPdCy@clay is synthesized and characterized. This palladium composite promotes the Sonogashira reaction of aryl iodides, bromides and chlorides with terminal alkynes in polyethylene glycol200 at 85 or 130 °C using 0.05–0.1 mol% of palladium loading under copper and phosphine free conditions. This supported palladacycle, OxPdCy@clay, showed a superior catalytic activity than dimeric oxime-palladacycles. Mechanistic studies about the heterogeneous or homogeneous nature of the catalyst show that catalyst is working mainly under heterogeneous conditions. This supported palladacycle OxPdCy@clay can be recycled by simple centrifugation and reused for at least nine consecutive runs with small decrease in activity.

Design, synthesis, and evaluation of chalcone analogues incorporate α,β-Unsaturated ketone functionality as anti-lung cancer agents via evoking ROS to induce pyroptosis

Chalcone, a natural structure, demonstrates many pharmacological activities including anticancer, and one promising mechanism is to modulate the generation of ROS. It has been known that pyroptosis is associated with anticancer effects, whereas there is fewer researches about ROS-mediated pyroptosis triggered by chemotherapy drugs. Moreover, incorporation of a α,β-unsaturated ketone unit into chalcone may be an effective strategy for development of chemotherapy drugs. Hence, a number of chalcone analogues bearing a α,β-unsaturated ketone were synthesized from chalcone analogues 1 with modest anticancer activities as the lead compound. Structure-activity relationship (SAR) studies confirmed the function of α,β-unsaturated ketone to improve anticancer activity. Notably, compound 8, bearing a α,β-unsaturated ketone, is the most potent inhibitor of cancer, with IC50 values on NCI-H460, A549 and H1975 cells of 2.3 ± 0.3, 3.2 ± 0.0 and 5.7 ± 1.4 μM, respectively. Besides, 8 showed antiproliferative ability against NCI-H460 cells in a time- and concentration-dependent manner through modulating ROS to induce caspase-3-mediated pyroptosis, and displayed a better safety profile in vivo. Overall, these results demonstrated that compound 8 is a candidate agent and a potential lead compound for development of chemotherapy drugs, and can be used as a probe to further examine the mechanism of ROS-dependent pyroptosis.

Chemoproteomics-enabled covalent ligand screen reveals a cysteine hotspot in reticulon 4 that impairs ER morphology and cancer pathogenicity

Chemical genetics has arisen as a powerful approach for identifying novel anti-cancer agents. However, a major bottleneck of this approach is identifying the targets of lead compounds that arise from screens. Here, we coupled the synthesis and screening of fragment-based cysteine-reactive covalent ligands with activity-based protein profiling (ABPP) chemoproteomic approaches to identify compounds that impair colorectal cancer pathogenicity and map the druggable hotspots targeted by these hits. Through this coupled approach, we discovered a cysteine-reactive acrylamide DKM 3-30 that significantly impaired colorectal cancer cell pathogenicity through targeting C1101 on reticulon 4 (RTN4). While little is known about the role of RTN4 in colorectal cancer, this protein has been established as a critical mediator of endoplasmic reticulum tubular network formation. We show here that covalent modification of C1101 on RTN4 by DKM 3-30 or genetic knockdown of RTN4 impairs endoplasmic reticulum and nuclear envelope morphology as well as colorectal cancer pathogenicity. We thus put forth RTN4 as a potential novel colorectal cancer therapeutic target and reveal a unique druggable hotspot within RTN4 that can be targeted by covalent ligands to impair colorectal cancer pathogenicity. Our results underscore the utility of coupling the screening of fragment-based covalent ligands with isoTOP-ABPP platforms for mining the proteome for novel druggable nodes that can be targeted for cancer therapy.

Efficient cu-catalyzed atom transfer radical addition reactions of fluoroalkylsulfonyl chlorides with electron-deficient alkenes induced by visible light

Fluoroalkylsulfonyl chlorides, RfSO2Cl, in which Rf=CF3, C4F9, CF2H, CH2F, and CH2CF3, are used as a source of fluorinated radicals to add fluoroalkyl groups to electron-deficient, unsaturated carbonyl compounds. Photochemical conditions, using Cu mediation, are used to produce the respective α-chloro-β-fluoroalkylcarbonyl products in excellent yields through an atom transfer radical addition (ATRA) process. Facile nucleophilic replacement of the α-chloro substituent is shown to lead to further diverse functionalization of the products.

Direct Photoredox-Catalyzed Reductive Difluoromethylation of Electron-Deficient Alkenes

Photoredox-catalyzed reductive difluoromethylation of electron-deficient alkenes was achieved in one step under tin-free, mild and neutral conditions. This protocol affords a facile method to introduce RCF2 (R=H, Ph, Me, and CH2N3) groups at sites β to electron-withdrawing groups. It was found that TTMS (tris(trimethylsilyl)silane) served nicely as both the H-atom donor and the electron donor in the catalytic cycle. Experimental and DFT computational results provided evidence that RCF2 (R=H, Ph, Me) radicals are nucleophilic in nature.