613-54-7Relevant academic research and scientific papers
New (arylalkyl)azole derivatives showing anticonvulsant effects could have VGSC and/or GABAAR affinity according to molecular modeling studies
Sari, Suat,Karakurt, Arzu,Uslu, Harun,Kaynak, F. Betül,?al??, ünsal,Dalkara, Sevim
, p. 407 - 416 (2016)
(Arylalkyl)azoles (AAAs) emerged as a novel class of antiepileptic agents with the invention of nafimidone and denzimol. Several AAA derivatives with potent anticonvulsant activities have been reported so far, however neurotoxicity was usually an issue. We prepared a set of ester derivatives of 1-(2-naphthyl)-2-(1H-1,2,4-triazol-1-yl)ethanone oxime and evaluated their anticonvulsant and neurotoxic effects in mice. Most of our compounds were protective against maximal electroshock (MES)- and/or subcutaneous metrazol (s.c. MET)-induced seizures whereas none of them showed neurotoxicity. Nafimidone and denzimol have an activity profile similar to that of phenytoin or carbamazepine, both of which are known to inhibit voltage-gated sodium channels (VGSCs) as well as to enhance γ-aminobutiric acid (GABA)-mediated response. In order to get insights into the effects of our compounds on VGSCs and A-type GABA receptors (GABAARs) we performed docking studies using homology model of Na+channel inner pore and GABAAR as docking scaffolds. We found that our compounds bind VGSCs in similar ways as phenytoin, carbamazepine, and lamotrigine. They showed strong affinity to benzodiazepine (BZD) binding site and their binding interactions were mainly complied with the experimental data and the reported BZD binding model.
A practical synthesis of α-bromo/iodo/chloroketones from olefins under visible-light irradiation conditions
Wang, Zhihui,Wang, Lei,Wang, Zhiming,Li, Pinhua,Zhang, Yicheng
supporting information, p. 429 - 432 (2020/02/29)
A practical synthesis of α-bromo/iodo/chloroketones from olefins under visible-light irradiation conditions has been developed. In the presence of PhI(OAc)2 as promoter and under ambient conditions, the reactions of styrenes and triiodomethane undergo the transformation smoothly to deliver the corresponding α-iodoketones without additional photocatalyst in good yields under sunlight irradiation. Meanwhile, the reactions of styrenes with tribromomethane and trichloromethane generate the desired α-bromoketones and α-chloroketones in high yields by using Ru(bpy)3Cl2 as a photocatalyst under blue LED (450–455 nm) irradiation.
High Chemo-/Stereoselectivity for Synthesis of Polysubstituted Monofluorinated Pyrimidyl Enol Ether Derivatives
Kang, Lei,Wang, Fang,Zhang, Jinlong,Yang, Huameng,Xia, Chungu,Qian, Jinlong,Jiang, Gaoxi
supporting information, p. 1669 - 1674 (2021/03/08)
A novel intramolecular Smiles rearrangement of α-fluoro-β-keto-pyrimidylsulfones (usually used as a carbon nucleophile) was developed, providing a versatile avenue for synthesis of tri/tetra-substituted monofluorinated pyrimidyl enol ethers. Among these, diverse (Z)-monofluorovinylsulfones and sulfinates were efficiently assembled by adding extra electrophile and fine-tuning reaction conditions. The process is triggered by a keto-enol tautomerism from enol oxyanion to pyrimidine 2-carbon, completely different from the classical carbon nucleophilic addition reaction approach.
Base-Catalyzed Intramolecular Defluorination/O-Arylation Reaction for the Synthesis of 3-Fluoro-1,4-oxathiine 4,4-Dioxide
Kang, Lei,Zhang, Jinlong,Yang, Huameng,Qian, Jinlong,Jiang, Gaoxi
supporting information, p. 785 - 789 (2021/04/09)
A novel process involving base-catalyzed intramolecular defluorination/O-arylation of readily available α-fluoro-β-one-sulfones was realized and provided a series of 3-fluoro-1,4-oxathiine 4,4-dioxide derivatives in good to excellent yields. Unlike traditional defluorination reactions with stoichiometric base as the deacid reagent, this process is triggered by a catalytic amount of base (TMG: tetramethylguanidine) and molecular sieves serve as both an adsorbent to remove HF acid and an activator to assist C-F bond cleavage.
An umpolung oxa-[2,3] sigmatropic rearrangement employing arynes for the synthesis of functionalized enol ethers
Gaykar, Rahul N.,George, Malini,Guin, Avishek,Bhattacharjee, Subrata,Biju, Akkattu T.
supporting information, p. 3447 - 3452 (2021/05/04)
An oxa-[2,3] sigmatropic rearrangement involving arynes is reported featuring the umpolung of ketones, where the C=O bond polarity is reversed. The in situ-generated sulfur ylides from β-keto thioethers and arynes undergo efficient rearrangement allowing the facile and robust synthesis of functionalized enol ethers in high yields and excellent functional group compatibility. Preliminary mechanistic studies rule out the possibility of Pummerer-type rearrangement operating in this case.
Antifungal activity of 1,4-dialkoxynaphthalen-2-acyl imidazolium salts by inducing apoptosis of pathogenic candida spp.
Lee, Jisue,Kim, Jae-Goo,Lee, Haena,Lee, Tae Hoon,Kim, Ki-Young,Kim, Hakwon
, p. 1 - 20 (2021/03/16)
Even though Candida spp. are staying commonly on human skin, it is also an opportunistic pathogenic fungus that can cause candidiasis. The emergence of resistant Candida strains and the toxicity of antifungal agents have encouraged the development of new classes of potent antifungal agents. Novel naphthalen-2-acyl imidazolium salts (NAIMSs), especially 1,4-dialkoxy-NAIMS from 1,4-dihydroxynaphthalene, were prepared and evaluated for antifungal activity. Those derivatives showed prominent anti-Candida activity with a minimum inhibitory concentration (MIC) of 3.125 to 6.26 μg/mL in 24 h based on microdilution antifungal susceptibility test. Among the tested com-pounds, NAIMS 7c showed strongest antifungal activity with 3.125 μg/mL MIC value compared with miconazole which showed 12.5 μg/mL MIC value against Candida spp., and more importantly >100 μg/mL MIC value against C. auris. The production of reactive oxygen species (ROS) was increased and JC-1 staining showed the loss of mitochondrial membrane potential in C. albicans by treatment with NAIMS 7c. The increased release of ultraviolet (UV) absorbing materials suggested that NAIMS 7c could cause cell busting. The expression of apoptosis-related genes was induced in C. albicans by NAIMS 7c treatment. Taken together, the synthetic NAIMSs are of high interest as novel antifungal agents given further in vivo examination.
Novel Aryl-Substituted Pyrimidones as Inhibitors of 3-Mercaptopyruvate Sulfurtransferase with Antiproliferative Efficacy in Colon Cancer
Bantzi, Marina,Augsburger, Fiona,Loup, Jérémie,Berset, Yan,Vasilakaki, Sofia,Myrianthopoulos, Vassilios,Mikros, Emmanuel,Szabo, Csaba,Bochet, Christian G.
, p. 6221 - 6240 (2021/05/06)
The enzyme 3-mercaptopyruvate sulfurtransferase (3-MST) is one of the more recently identified mammalian sources of H2S. A recent study identified several novel 3-MST inhibitors with micromolar potency. Among those, (2-[(4-hydroxy-6-methylpyrimidin-2-yl)sulfanyl]-1-(naphthalen-1-yl)ethan-1-one) or HMPSNE was found to be the most potent and selective. We now took the central core of this compound and modified the pyrimidone and the arylketone sides independently. A 63-compound library was synthesized; compounds were tested for H2S generation from recombinant 3-MST in vitro. Active compounds were subsequently tested to elucidate their potency and selectivity. Computer modeling studies have delineated some of the key structural features necessary for binding to the 3-MST's active site. Six novel 3-MST inhibitors were tested in cell-based assays: they exerted inhibitory effects in murine MC38 and CT26 colon cancer cell proliferation; the antiproliferative effect of the compound with the highest potency and best cell-based activity (1b) was also confirmed on the growth of MC38 tumors in mice.
Chiral Bidentate Phosphoramidite-Pd Catalyzed Asymmetric Decarboxylative Dipolar Cycloaddition for Multistereogenic Tetrahydrofurans with Cyclic N-Sulfonyl Ketimine Moieties
Lv, Hao-Peng,Yang, Xiao-Peng,Wang, Bai-Lin,Yang, Hao-Di,Wang, Xing-Wang,Wang, Zheng
supporting information, p. 4715 - 4720 (2021/06/28)
An asymmetric [3 + 2] cycloaddition of vinyl ethylenecarbonates (VECs) and (E)-3-arylvinyl substituted benzo[d] isothiazole 1,1-dioxides has been developed using the Pd complex of a bidentate phosphoramidite (Me-BIPAM) as the catalyst, providing a wide variety of chiral multistereogenic vinyltetrahydrofurans in good yields with excellent diastereo- and enantioselectivities (up to >20:1 dr, 99% ee).
Nickel-catalyzed asymmetric arylative cyclization of N-alkynones: Efficient access to 1,2,3,6-tetrahydropyridines with a tertiary alcohol
He, Lin,Li, Ruihao,Li, Wendian,Lv, Hui,Tian, Jiangyan
supporting information, (2021/07/06)
Nickel/(S)-t-Bu-PHOX complex catalyzed asymmetric arylative cyclization of N-alkynones has been achieved, delivering 1,2,3,6-tetrahydropyridines containing a chiral tertiary alcohol in high yields and excellent enantioselectivities, which provides efficient access to chiral tetrahydropyridine and piperidine analogues.
Oxidation Potential-Guided Electrochemical Radical-Radical Cross-Coupling Approaches to 3-Sulfonylated Imidazopyridines and Indolizines
Kim, Wansoo,Kim, Hun Young,Oh, Kyungsoo
, p. 15973 - 15991 (2021/07/26)
Oxidation potential-guided electrochemical radical-radical cross-coupling reactions between N-heteroarenes and sodium sulfinates have been established. Thus, simple cyclic voltammetry measurement of substrates predicts the likelihood of successful radical-radical coupling reactions, allowing the simple and direct synthetic access to 3-sulfonylated imidazopyridines and indolizines. The developed electrochemical radical-radical cross-coupling reactions to sulfonylated N-heteroarenes boast the green synthetic nature of the reactions that are oxidant- and metal-free.
