3099-31-8Relevant academic research and scientific papers
Synthesis and antitumor activity of novel pyridinium fullerene derivatives
Yasuno, Takumi,Ohe, Tomoyuki,Ikeda, Hitomi,Takahashi, Kyoko,Nakamura, Shigeo,Mashino, Tadahiko
, p. 6325 - 6337 (2019/08/28)
Purpose: We have previously reported that some cationic fullerene derivatives exhibited anticancer activity, and they are expected to be a potential lead compound for an anti-drug resistant cancer agent. However, they are bis-adducts and a mixture of multiple regioisomers, which cannot be readily separated due to the variability of substituent positions on the fullerene cage. To overcome this issue, we evaluated the antiproliferative activities of a set of mono-adduct derivatives and examined their structure-activity relationship. In addition, the in vivo antitumor activity of selected derivatives was also examined. Methods: Nineteen pyridinium fullerene derivatives were newly designed and synthesized in this study. Their antiproliferative activities were evaluated using several cancer cell lines including drug-resistant cells. Furthermore, in vivo antitumor activity of several derivatives was investigated in mouse xenograft model of human lung cancer. Results: The derivatives inhibited the proliferation of cancer cell lines, including cisplatin-resistant cells and doxorubicin-resistant cells. It was also shown that compound 10 (10 μM), 13 (10 μM) and cis-14 (10 μM) induced the intracellular oxidative stress. In addition, compound 13 (20 mg/kg) and cis-14 (15 mg/kg) significantly exhibited antitumor activity in mouse xenograft model of human lung cancer. Conclusion: We synthesized a novel set of mono-adduct fullerene derivatives functionalized with pyridinium groups and found that most of them show potent antiproliferative activities against cancer cell lines and some of them show significant antitumor activities in vivo. We propose that these fullerene derivatives serve as the lead compounds for a novel type of antitumor agents.
Improved Electrocatalytic CO2 Reduction with Palladium bis(NHC) Pincer Complexes Bearing Cationic Side Chains
Deluca, Emile E.,Xu, Zhen,Lam, Jasper,Wolf, Michael O.
supporting information, p. 1330 - 1343 (2019/03/28)
Stabilizing interactions between charged electrocatalytic intermediates and a series of cationic residues were explored through the synthesis and characterization of six palladium bis(N-heterocyclic carbene) (NHC) complexes bearing unique onium functionalities. The presence of a positively charged, pendant substituent was found to mediate electrode kinetics and facilitate CO2 coordination to the catalytic center in a systematic fashion. The introduction of cationic moieties into this system is shown to enhance catalytic selectivity for the conversion of CO2 to CO by as much as 5 times that of an alkyl-bearing analog. A combination of electrochemical experiments and computational analysis demonstrates that catalyst performance benefits most from a bulky onium unit tethered to the catalyst through a flexible linker. This behavior was interpreted as a preference for a wide, hydrophobic reaction pocket that allows for the unhindered formation of catalytic intermediates and mediated interaction with the solution.
A 2 - chloro -5 - nitrapyrin preparation method
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Paragraph 0031-0032, (2019/03/15)
The invention discloses a 2 - chloro - 5 - trichloromethyl pyridine method, comprises the following steps: (1) the 3 - methyl pyridine is mixed with a solvent, the vaporization of the drops in the vaporization vessel, then in order to inert gas as a carrier gas, to form raw material steam; (2) dry Cl respectively2 The raw material and the steam is sent to the quartz tube catalyst [...] generating vapor phase chlorination reaction, reaction material after the condensation, rectification to obtain 2 - chloro - 5 - trichloromethyl pyridine. The invention relates to a 2 - chloro - 5 - trichloromethyl pyridine method, with raw materials are easy, low cost, easy to operate, simple process and the like.
NMP-mediated chlorination of aliphatic alcohols with aryl sulfonyl chloride for the synthesis of alkyl chlorides
Zheng, Dagui,Mao, Liu-Liang,Zhu, Xian-Hong,Zhou, An-Xi
supporting information, p. 2793 - 2800 (2018/11/06)
NMP-mediated chlorination of aliphatic alcohols has been developed for the synthesis of alkyl chlorides. This facile, efficient and practical approach used simple and readily available aryl sulfonyl chlorides as the chlorination reagent for the construction of C–Cl bond in good to excellent yields with mild conditions and broad substrate scope.
Potent and Selective Human Neuronal Nitric Oxide Synthase Inhibition by Optimization of the 2-Aminopyridine-Based Scaffold with a Pyridine Linker
Wang, Heng-Yen,Qin, Yajuan,Li, Huiying,Roman, Linda J.,Martásek, Pavel,Poulos, Thomas L.,Silverman, Richard B.
supporting information, p. 4913 - 4925 (2016/06/13)
Neuronal nitric oxide synthase (nNOS) is an important therapeutic target for the treatment of various neurodegenerative disorders. A major challenge in the design of nNOS inhibitors focuses on potency in humans and selectivity over other NOS isoforms. Here we report potent and selective human nNOS inhibitors based on the 2-aminopyridine scaffold with a central pyridine linker. Compound 14j, the most promising inhibitor in this study, exhibits excellent potency for rat nNOS (Ki = 16 nM) with 828-fold n/e and 118-fold n/i selectivity with a Ki value of 13 nM against human nNOS with 1761-fold human n/e selectivity. Compound 14j also displayed good metabolic stability in human liver microsomes, low plasma protein binding, and minimal binding to cytochromes P450 (CYPs), although it had little to no Caco-2 permeability.
Antimalarial and structural studies of pyridine-containing inhibitors of 1-deoxyxylulose-5-phosphate reductoisomerase
Xue, Jian,Diao, Jiasheng,Cai, Guobin,Deng, Lisheng,Zheng, Baisong,Yao, Yuan,Song, Yongcheng
supporting information, p. 278 - 282 (2013/03/29)
1-Deoxy-d-xylulose-5-phosphate reductoisomerase (DXR) in the nonmevalonate isoprene biosynthesis pathway is a target for developing antimalarial drugs. Fosmidomycin, a potent DXR inhibitor, showed safety as well as efficacy against Plasmodium falciparum malaria in clinical trials. On the basis of our previous quantitative structure-activity relationship (QSAR) and crystallographic studies, several novel pyridine-containing fosmidomycin derivatives were designed, synthesized, and found to be highly potent inhibitors of P. falciparum DXR (PfDXR) having Ki values of 1.9-13 nM, with the best one being ～11× more active than fosmidomycin. These compounds also potently block the proliferation of multidrug resistant P. falciparum with EC 50 values as low as 170 nM. A 2.3 A? crystal structure of PfDXR in complex with one of the inhibitors is reported, showing that the flexible loop of the protein undergoes conformational changes upon ligand binding and a hydrogen bond and favorable hydrophobic interactions between the pyridine group and the PfDXR account for the enhanced activity.
Discovery of highly potent and selective D4 ligands by interactive SAR study
Abdelfattah, Mohamed A.O.,Lehmann, Jochen,Abadi, Ashraf H.
supporting information, p. 5077 - 5081 (2013/09/12)
A series of thienylmethylphenylpiperazins was synthesized and tested for affinity towards the five subtypes of dopaminergic receptors. Compound 5f showed more than 1000 folds selectivity to D4 receptors; analogue 5e showed the highest affinity to D4 receptors with Ki 3.9 nM. An interactive SAR approach was adopted and lead to compound 14a with Ki (D4) as low as 0.03 nM. Molecular docking studies showed a potential, first to report arene cation interaction between the D4 unique residue Arg-186 and the ligands' arene moiety, explaining the importance of having a strong negative electrostatic potential at this area of the compound structure.
Molecular tectonics: Pyridyl containing thiacalix[4]arene based tectons for the generation of 2- and 3-D silver coordination networks
Ovsyannikov,Lang,Ferlay,Solovieva,Antipin,Konovalov,Kyritsakas,Hosseini
, p. 116 - 126 (2013/02/22)
Three new organic tectons (2-4) based on the p-tert-butylthiacalix[4]arene backbone, blocked in the 1,3-alternate conformation, bearing four pyridyl coordinating moieties, have been synthesised and characterised in the solid state. The ligands are positional isomers and differ by the position of the N atom on the pyridyl unit (ortho for 2, meta for 3 and para for 4). Their combination with the Ag+ cation leads, reproducibly, to the formation of 2- and 3-D infinite silver coordination networks. Independent of the nature of the anion, the combination of 2 offering four (N,S) type chelates with the Ag+ cation affords an unprecedented diamond type 3D network. Both 3 and 4, behaving as tetrakis monodentate ligands, lead to the formation of 2-D architectures. The Royal Society of Chemistry 2013.
Efficient synthesis of a new series of piperidine ring-modified analogs of (±)-threo-methyl phenyl(piperidin-2-yl)acetate
Ojo, Babatunde
experimental part, p. 1731 - 1745 (2012/06/29)
A series of novel piperidine ring modified analogs of (±)-threo- methyl phenyl (piperidin-2-yl)acetate was synthesized by direct alkylation and reductive amination procedure, using sodium borohydride over molecular sieves. The chemical structures of these compounds were established based on mass spectra, 1H NMR spectra, and CHN elemental analysis data. Several significant modifications in the literature methodologies were made to make the reaction more efficient, and good yields were generally obtained. Copyright Taylor & Francis Group, LLC.
Treatment of alcohols with tosyl chloride does not always lead to the formation of tosylates
Ding, Rui,He, Yong,Wang, Xiao,Xu, Jingli,Chen, Yurong,Feng, Man,Qi, Chuanmin
experimental part, p. 5665 - 5673 (2011/09/20)
Treatment of substituted benzyl alcohols with tosyl chloride resulted in the formation of the corresponding chlorides, not the usual tosylates. A series of experiments demonstrated that it was possible to predict whether chlorination or tosylation would occur for substituted benzyl alcohols and pyridine methanols. Treatment of electron withdrawing group-substituted benzyl alcohols with tosyl chloride gave the corresponding chlorides in moderate yields under mild conditions, which provided a simple way to directly prepare chlorides from alcohols.
