20766-31-8Relevant articles and documents
Polysubstituted Indole Synthesis via Palladium/Norbornene Cooperative Catalysis of Oxime Esters
Liu, Jiechun,Lin, Haojiang,Jiang, Huanfeng,Huang, Liangbin
supporting information, p. 484 - 489 (2022/01/20)
Polysubstituted indoles are prevalent in pharmaceuticals, agrochemicals, and organic materials. Presented herein is the fact that polyfunctionalized indoles can be efficiently constructed from easily accessible oxime esters and aryl iodides, involving a palladium/norbornene synergistic synthesis. The reaction is enabled by a unique class of electrophiles in palladium/norbornene cooperative catalysis, which are oxime esters derived from simple ketone. The broad substrate scope and high functional group tolerance could make this method attractive for the synthesis of polysubstituted indoles.
Novel substituted 5-methyl-4-acylaminoisoxazoles as antimitotic agents: Evaluation of selectivity to LNCaP cancer cells
Averina, Elena B.,Bunev, Alexander S.,Gracheva, Yulia A.,Grishin, Yuri K.,Kuznetsov, Sergei A.,Kuznetsova, Tamara S.,Milaeva, Elena R.,Palyulin, Vladimir A.,Radchenko, Eugene V.,Sadovnikov, Kirill S.,Shevtsov, Pavel N.,Shevtsova, Elena F.,Shtil, Alexander A.,Vasilenko, Dmitry A.,Vasilichin, Vladislav A.,Zefirov, Nikolay A.,Zefirova, Olga N.
, (2022/02/07)
A series of novel antimitotic agents was designed using the replacement of heterocyclic cores in two tubulin-targeting lead molecules with the acylated 4-aminoisoxazole moiety. Target compounds were synthesized via heterocyclization of β-aryl-substituted vinylketones by tert-butyl nitrite in the presence of water as a key step. 4-Methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1aa) was found to stimulate partial depolymerization of microtubules of human lung carcinoma A549 cells at a high concentration of 100 μM and to totally inhibit cell growth (IC50 = 0.99 μM) and cell viability (IC50 = 0.271 μM) in the nanomolar to submicromolar concentration range. These data provide evidence of the multitarget profile of the cytotoxic action of compound 1aa. The SAR study demonstrated that the 3,4,5-trimethoxyphenyl residue is the key structural parameter determining the efficiency both towards tubulin and other molecular targets. The cytotoxicity of 3-methyl-N-[5-methyl-3-(3,4,5-trimethoxyphenyl)isoxazol-4-yl]benzamide (1ab) to the androgen-sensitive human prostate adenocarcinoma cancer cell line LNCaP (IC50 = 0.301 μM) was approximately one order of magnitude higher than that to the conditionally normal cells lines WI-26 VA4 (IC50 = 2.26 μM) and human umbilical vein endothelial cells (IC50 = 5.58 μM) and significantly higher than that to primary fibroblasts (IC50 > 75 μM).
8-Hydroxyquinolin-2(1H)-one analogues as potential β2-agonists: Design, synthesis and activity study
Xing, Gang,Zhi, Zhengxing,Yi, Ce,Zou, Jitian,Jing, Xuefeng,Yiu-Ho Woo, Anthony,Lin, Bin,Pan, Li,Zhang, Yuyang,Cheng, Maosheng
, (2021/07/19)
β2-Agonists that bind to plasmalemmal β2-adrenoceptors causing cAMP accumulation are widely used as bronchodilators in chronic respiratory diseases. Here, we designed and synthesized a group of 8-hydroxyquinolin-2(1H)-one analogues and studied their β2-agonistic activities with a cellular cAMP assay. Compounds B05 and C08 were identified as potent (EC50 2-agonists among the compounds tested. They behaved as partial β2-agonists in non-overexpressed HEK293 cells, and possessed rapid smooth muscle relaxant actions and long duration of action in isolated guinea pig tracheal strip preparations. In summary, B05 and C08 are β2-agonists with potential applicability in chronic respiratory diseases.
Piperlongumine derivative as well as preparation method and application thereof
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Paragraph 0033; 0040; 0069-0072, (2021/01/28)
The invention discloses a Piperlongumine derivative as well as a preparation method and application thereof. The Piperlongumine derivative has the following structure: the Piperlongumine derivative provided by the invention contains a plurality of Michael addition receptor units, and the novel structure improves the electrophilicity, so that the Piperlongumine derivative has good protein targetingpotential, and the Piperlongumine derivative has a good inhibition effect on thioredoxin reductase; in an antitumor bioactive in-vitro screening experiment, the derivative also has a certain inhibition effect on the growth of tumor cells, and meanwhile, the derivative has an effect of promoting the generation of active oxygen in A549 human lung cancer cells.
Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs
He, Wenfei,Wang, Jingsong,Jin, Qiling,Zhang, Jiafeng,Liu, Yugang,Jin, Zewu,Wang, Hua,Hu, Linya,Zhu, Lu,Shen, Mengya,Huang, Lili,Huang, Shengwei,Li, Wulan,Zhuge, Qichuan,Wu, Jianzhang
, (2021/07/06)
Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure–activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.
Sequential Two-Step Stereoselective Amination of Allylic Alcohols through the Combination of Laccases and Amine Transaminases
Albarrán-Velo, Jesús,Lavandera, Iván,Gotor-Fernández, Vicente
, p. 200 - 211 (2019/12/03)
A sequential two-step chemoenzymatic methodology for the stereoselective synthesis of (3E)-4-(het)arylbut-3-en-2-amines in a highly selective manner and under mild reaction conditions is described. The approach consists of oxidation of the corresponding racemic alcohol precursors by the use of a catalytic system made up of the laccase from Trametes versicolor and the oxy-radical TEMPO, followed by the asymmetric reductive bio-transamination of the corresponding ketone intermediates. Optimisation of the oxidation reaction, exhaustive amine transaminase screening for the bio-transaminations and the compatibility of the two enzymatic reactions were studied in depth in search of a design of a compatible sequential cascade. This synthetic strategy was successful and the combinations of enzymes displayed a broad substrate scope, with 16 chiral amines being obtained in moderate to good isolated yields (29–75 %) and with excellent enantiomeric excess values (94 to >99 %). Interestingly, both amine enantiomers can be achieved, depending on the selectivity of the amine transaminase employed in the system.
One-pot two-step chemoenzymatic deracemization of allylic alcohols using laccases and alcohol dehydrogenases
Albarrán-Velo, Jesús,Gotor-Fernández, Vicente,Lavandera, Iván
, (2020/07/03)
A series of enantioenriched (hetero)aromatic secondary allylic alcohols has been synthesized through deracemization of the corresponding racemic mixtures combining a non-selective chemoenzymatic oxidation (laccase from Trametes versicolor and oxy-radical TEMPO) and a stereoselective biocatalyzed reduction (lyophilized cells of E. coli overexpressing an alcohol dehydrogenase, ADH). Both steps were performed in aqueous medium under very mild reaction conditions. After optimization, a sequential one-pot two-step protocol was set up, obtaining the corresponding chiral alcohols in moderate to high conversions (48–95%) and enantiomeric excess (65->99% ee). Depending on the ADH stereopreference, both antipodes from these valuable chiral synthons could be prepared, even at preparative scale (119?178 mg), in a straightforward manner.
Discovery and Characterization of Pure RhlR Antagonists against Pseudomonas aeruginosa Infections
Nam, SangJin,Ham, So-Young,Kwon, Hongmok,Kim, Han-Shin,Moon, Suhyun,Lee, Jeong-Hoon,Lim, Taehyeong,Son, Sang-Hyun,Park, Hee-Deung,Byun, Youngjoo
supporting information, p. 8388 - 8407 (2020/09/21)
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic human pathogen that forms biofilms and produces virulence factors via quorum sensing (QS). Blocking the QS system in P. aeruginosa is an excellent strategy to reduce biofilm formation and the production of virulence factors. RhlR plays an essential role in the QS system of P. aeruginosa. We synthesized 55 analogues based on the chemical structure of 4-gingerol and evaluated their RhlR inhibitory activities using the cell-based reporter strain assay. Comprehensive structure-activity relationship studies identified the alkynyl ketone 30 as the most potent RhlR antagonist. This compound displayed selective RhlR antagonism over LasR and PqsR, strong inhibition of biofilm formation, and reduced production of virulence factors in P. aeruginosa. Furthermore, the survival rate of Tenebrio molitor larvae treated with 30 in vivo greatly improved. Therefore, compound 30, a pure RhlR antagonist, can be utilized for developing QS-modulating molecules in the control of P. aeruginosa infections.
Iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes
Chen, Weifeng,Jiang, Kezhi,Xue, Yuntian,Yan, Yaolong,Yang, Lei
, p. 14720 - 14724 (2020/04/27)
The first iodine/water-mediated deprotective oxidation of allylic ethers to access α,β-unsaturated ketones and aldehydes was achieved. The reaction tolerates a wide range of functionalities. Furthermore, this protocol was found to be applicable to the oxidative transformation of allylic acetates. The proposed mechanism involves an oxygen transfer from solvent water to the carbonyl products.
Use of a switchable-hydrophilicity solvent as both a solvent and a catalyst in aldol condensation
Poole, Hailey,Gauthier, Jeremy,Vanderveen, Jesse R.,Jessop, Philip G.,Lee, Roland
supporting information, p. 6263 - 6267 (2019/12/03)
A switchable-hydrophilicity solvent, N,N-dimethylcyclohexylamine, was used as a recyclable catalyst and solvent for aldol condensation, giving >97% pure product in 94% isolated yield without the need for purification or additional solvents. CO2-triggered separation produced yields greater than conventional workup and allowed facile recycling of the amine.
