4845-49-2Relevant academic research and scientific papers
Stereoselective Assembly of Multifunctional Spirocyclohexene Pyrazolones That Induce Autophagy-Dependent Apoptosis in Colorectal Cancer Cells
Li, Xiang,Chen, Fei-Yu,Kang, Jing-Wen,Zhou, Jin,Peng, Cheng,Huang, Wei,Zhou, Mu-Ke,He, Gu,Han, Bo
, p. 9138 - 9150 (2019)
Enantio- and diastereoselective synthesis of multifunctional spiropyrazolone scaffolds has been achieved using secondary amine-catalyzed [4 + 2] annulations of α,β,γ,δ-unsaturated pyrazolones with aldehydes. The pyrazolone substrates serve as C4 synthons to produce 6-membered, carbocycle-based, chiral spiropyrazolone derivatives. The synthesized chiral compounds showed potent toxicity against a panel of cancer cell lines. The most potent compound 3h-induced cell cycle arrest and macroautophagy in HCT116 colorectal cancer cells, triggering autophagy-dependent apoptotic cell death.
Palladium catalysed hydrolysis-free arylation of aliphatic nitriles for the synthesis of 4-arylquinolin-2-one/pyrazolone derivatives
Krishna Reddy, Singarajanahalli Mundarinti,Prasanna Kumari, Subramaniyan,Selva Ganesan, Subramaniapillai
, (2021/08/03)
Palladium catalysed addition of arylboronic acid to the readily available 2-cyano-(N-aryl)-acetamide or ethyl-2-cyanoacetate followed by subsequent reaction transform them into the biologically significant 4-arylquinolin-2-one or pyrazolone derivatives. The reaction conditions are robust enough to prevent the hydrolysis of ester/amide moiety during arylation. In addition, the unactivated nitrile moiety in the acetonitrile also converted to the corresponding acetophenone derivative.
Catalytic Asymmetric Addition of Diorganozinc Reagents to Pyrazole-4,5-Diones and Indoline-2,3-Diones
Wang, Rong-Hui,Li, Ya-Ling,He, Hong-Jiao,Xiao, You-Cai,Chen, Fen-Er
supporting information, p. 4302 - 4306 (2021/02/16)
The catalytic enantioselective diorganozinc additions to cyclic diketones including pyrazolin-4,5-diones and isatins have been developed. In the presence of morpholine-containing chiral amino alcohol ligand, the corresponding chiral cyclic tertiary alcohols were produced in good to excellent yields (up to 97 %) and enantioselectivities (up to 95 % ee). The notable feature of this protocol includes its mild reaction conditions, Lewis acid additives free and broad functional group tolerance.
Catalytic System-Controlled Divergent Reaction Strategies for the Construction of Diversified Spiropyrazolone Skeletons from Pyrazolidinones and Diazopyrazolones
Fang, Feifei,Han, Xu,Hu, Shulei,Li, Chunpu,Liu, Hong,Wang, Qian,Wang, Run,Zhou, Yu
supporting information, p. 21327 - 21333 (2021/08/20)
A catalytic system-controlled divergent reaction strategy was here reported to construct four types of intriguing spiroheterocyclic skeletons from simple and readily available starting materials via a precise chemical bond activation/[n+1] annulation cascade. The tetraazaspiroheterocyclic and trizazspiroheterocyclic scaffolds could be independently constructed by a selective N?N bond activation/[n+1] annulation cascade, a C(sp2)-H activation/[4+1] annulation and a novel tandem C(sp2)-H/C(sp3)?H bond activation/[4+1] annulation strategy, along with a broad scope of substrates, moderate to excellent yields and valuable transformations. More importantly, in these transformations, we are the first time to capture a N?N bond activation and a C(sp3)?H bond activation of pyrazolidinones under different catalytic system.
Rhodium-Catalyzed [4+2] Annulation of N-Aryl Pyrazolones with Diazo Compounds To Access Pyrazolone-Fused Cinnolines
Dhole, Sandip,Huang, Wan-Wen,Huang, Ying-Ti,Lin, Chih-Yu,Sun, Chung-Ming
supporting information, p. 4984 - 4992 (2021/09/28)
An efficient synthesis of novel dinitrogen-fused heterocycles such as pyrazolo[1,2-a]cinnoline derivatives have been accomplished by the rhodium(III)-catalyzed reaction of N-arylpyrazol-5-ones with α-diazo compounds. This reaction proceeds through a cascade C?H activation/intramolecular cyclization with a broad substrate scope. Furthermore, this protocol is successfully extended to the unusual phosphorus-containing α-diazo compounds and cyclic diazo compounds as the cross-coupling partners to deliver the two new kinds of pyrazolo[1,2-a]cinnolinones. The control experiments were performed to reveal insight into the mechanism of this reaction, involving reversible C?H activation, migratory insertion of the diazo compound, and cascade cyclization as the key steps of the transformation. Moreover, gram-scale synthesis and further transformation of the target product demonstrate the synthetic utility of the present protocol.
Electrochemical synthesis of versatile ammonium oxides under metal catalyst-, exogenous-oxidant-, and exogenous-electrolyte-free conditions
Yuan, Yong,Li, Liang-Sen,Zhang, Lin,Wang, Feng,Jiang, Lin,Zuo, Lin,Wang, Qi,Hu, Jian-Guo,Lei, Aiwen
, p. 2768 - 2771 (2021/03/23)
An electrochemical oxidative cross-coupling reaction between 2.5-substituted-pyrazolin-5-ones and ammonium thiocyanate has been developed, which resulted in a series of unprecedented cross-coupling products under metal catalyst-, exogenous-oxidant-, and exogenous-electrolyte-free conditions. It is worth noting that since the resulting cross-coupling products are nearly insoluble in MeCN, the pure product could be afforded without silica gel column purification. In addition, the prepared ammonium oxides are versatile building blocks for synthesizing functionalized pyrazole derivatives.
DMSO as a Methine Source in TFA-Mediated One-Pot Tandem Regioselective Synthesis of 3-Substituted-1-Aryl-1 H-Pyrazolo-[3,4- b]quinolines from Anilines and Pyrazolones
Yadav, Pushpendra,Awasthi, Annapurna,Gokulnath, Sabapathi,Tiwari, Dharmendra Kumar
, p. 2658 - 2666 (2021/02/01)
An acid-mediated and DMSO participant one-pot tandem synthesis of 3-substituted-1-aryl-1H-pyrazolo-[3,4- b]quinoline from readily available anilines and pyrazolones was achieved. This method enables regioselective construction of the valuable heterocycles under transition-metal and oxidant-free conditions in which DMSO acts as a methine source as well as solvent making this process an environmentally benign approach. A broad range of diversely substituted aryl amines and pyrazolines are successfully employed in this reaction to access a series of pyrazolo[4,3-c]quinolones through a novel cascade mechanism. Furthermore, the application and mechanistic studies of the present methodology also demonstrated.
Synthesis and cytotoxic evaluation of some substituted 5-pyrazolones and their urea derivatives
Erturk, Aliye Gediz,Omerustaoglu, Hilal
, (2020/02/22)
In this paper, a series of new substituted-5-pyrazolones were first synthesized, then formulated by the Vilsmeier–Haack reaction to obtain substituted-4-carbaldehyde-5-pyrazolones. In the final step, when urea was reacted with formulated pyrazolones, we found that, instead of the C=N bond in azomethine form, the compounds tautomerized to form a series of novel pyrazole-4ylidenemethylurea structures. The structures of these compounds were elucidated by FTIR, 1H, 13C NMR, LC-MS/MS, and elemental analysis methods. The cytotoxic and antioxidant effects of substituted 5-pyrazolones and their pyrazolone-urea derivatives were investigated in metastatic A431 and noncancerous HaCaT human keratinocytes by a mitochondrial activity test. The effects of the compounds on the migration of cancerous and noncancerous cell lines were investigated by using a cell scratch assay. The General Linear Model, Statistical Package for Social Sciences (SPSS v26) was used to determine if there was a statistically significant difference between the control and the treatment groups. Four of the nine compounds showed an antioxidant effect. All 5-pyrazolone-urea compounds showed higher toxicity (p 0.05) in cancerous A431 cells compared to noncancerous cells at all time points. All compounds also showed a biphasic hormetic effect. Four of the nine compounds inhibited cell migration.
"on water" palladium catalyzed diastereoselective boronic acid addition to structurally diverse cyclopropane nitriles
Das, Asish R.,Das, Dwaipayan,Mukherjee, Prasun
, p. 8886 - 8898 (2020/11/23)
An efficient palladium catalyzed diastereoselective addition of arylboronic acids to complex spirocyclopropyl dinitriles is developed in the presence of a catalytic amount of 4-dodecylbenzenesulphonic acid (DBSA) as a Br?nsted acid surfactant in aqueous media. The protocol is also found to be highly effective when different types of nitrile compounds and organo-boron compounds are used. The overall reaction has been found to be very cost efficient since it requires low catalyst loading, mild thermal energy and short reaction time. Wide substrate scope, operational simplicity, good to excellent product yield, and use of green solvents make the reaction a practical route to transform nitrile into a keto functionality in biorelevant heterocyclic scaffolds. The scale-up synthesis of the target scaffolds can also be achieved with ease which also signifies the practicability of this protocol. This journal is
Targeting fungal virulence factor by small molecules: Structure-based discovery of novel secreted aspartic protease 2 (SAP2) inhibitors
Dong, Guoqiang,Han, Guiyan,Li, Chenglan,Liu, Na,Liu, Yang,Sheng, Chunquan,Tu, Jie,Wu, Shanchao
supporting information, (2020/07/06)
Secreted aspartic protease 2 (SAP2), a kind of virulence factor, is an emerging new antifungal target. Using docking-based virtual screening and structure-based inhibitor design, a series of novel SAP2 inhibitors were successfully identified. Among them, indolone derivative 24a showed potent SAP2 inhibitory activity (IC50 = 0.92 μM). It blocked fungi biofilm and hypha formation by down-regulating the expression of genes SAP2, ECE1, ALS3 and EFG1. As a virulence factor inhibitor, compound 24a was inactive in vitro and showed potent in vivo efficacy in a murine model of invasive candidiasis. It represents a promising lead compound for the discovery of novel antifungal agents.
