39755-95-8Relevant articles and documents
A Unified Catalytic Asymmetric (4+1) and (5+1) Annulation Strategy to Access Chiral Spirooxindole-Fused Oxacycles
Gao, Min,Gong, Xiangnan,Hu, Lin,Luo, Yanshu,Xia, Yuanzhi,Xu, Qianlan,Zhao, Yukun
supporting information, p. 19813 - 19820 (2021/08/03)
A unified catalytic asymmetric (N+1) (N=4, 5) annulation reaction of oxindoles with bifunctional peroxides has been achieved in the presence of a chiral phase-transfer catalyst (PTC). This general strategy utilizes peroxides as unique bielectrophilic four- or five-atom synthons to participate in the C?C and the subsequent umpolung C?O bond-forming reactions with one-carbon unit nucleophiles, thus providing a distinct method to access the valuable chiral spirooxindole-tetrahydrofurans and -tetrahydropyrans with good yields and high enantioselectivities under mild conditions. DFT calculations were performed to rationalize the origin of high enantioselectivity. The gram-scale syntheses and synthetic utility of the resultant products were also demonstrated.
Discovery of Novel Dual-Target Inhibitor of Bromodomain-Containing Protein 4/Casein Kinase 2 Inducing Apoptosis and Autophagy-Associated Cell Death for Triple-Negative Breast Cancer Therapy
Chen, Juncheng,Chiang, Cheng-Ming,He, Gu,Liu, Bo,Liu, Jie,Ouyang, Liang,Tang, Pan,Wang, Guan,Yang, Chengcan,Ye, Tinghong,Zhang, Jifa,Zhang, Jin,Zou, Ling
, p. 18025 - 18053 (2022/01/03)
Bromodomain-containing protein 4 (BRD4) is an attractive epigenetic target in human cancers. Inhibiting the phosphorylation of BRD4 by casein kinase 2 (CK2) is a potential strategy to overcome drug resistance in cancer therapy. The present study describes the synthesis of multiple BRD4–CK2 dual inhibitors based on rational drug design, structure–activity relationship, and in vitro and in vivo evaluations, and 44e was identified to possess potent and balanced activities against BRD4 (IC50 = 180 nM) and CK2 (IC50 = 230 nM). In vitro experiments show that 44e could inhibit the proliferation and induce apoptosis and autophagy-associated cell death of MDA-MB-231 and MDA-MB-468 cells. In two in vivo xenograft mouse models, 44e displays potent anticancer activity without obvious toxicities. Taken together, we successfully synthesized the first highly effective BRD4–CK2 dual inhibitor, which is expected to be an attractive therapeutic strategy for triple-negative breast cancer (TNBC).
Metal-free synthesis of benzimidazo[1,2-c]quinazolin-6-ones with indole and benzenediamine oxidized by I2/TBHP
Dai, Zhen,Li, Songhua,Li, Yunyi,Feng, Lei,Ma, Chen
supporting information, p. 2012 - 2017 (2019/02/20)
A variety of benzimidazo[1,2-c]quinazolin-6-ones derivatives can be accessed in moderate to good yields under simple and metal-free reaction conditions using indoles and o-benzenediamines oxidized by iodine and TBHP. This procedure works in reasonable yields for different indoles as well as o-benzenediamines thus may provide a good synthesis of quinazolinones. A TBHP oxidized ring expansion reaction mechanism that explains the synthesis of benzimidazo[1,2-c]quinazolin-6-ones were reported.
Method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid
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Paragraph 0024; 0053, (2018/09/08)
The invention discloses a method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid. The method comprises the following steps: a catalytic amount of catalyst copper iodide, indole, a derivative of the indole and peroxyacetic acid are added into a reaction vessel, wherein the indole, the derivative of the indole and the peroxyacetic acid are usedas raw materials, ethanol is used as a solvent, the reaction vessel is placed into a microwave reaction instrument, a reaction is performed at certain temperature and power, after a certain time, reduced-pressure concentration is performed, and a product is purified by column chromatography. The method provided by the invention is a method having novel raw materials, simple operation and high efficiency used for preparing a benzimidazole derivative; and compared with the prior art, the method provided by the invention has an obviously-accelerated reaction speed than that under conventional heating, mild reaction conditions, simple operation, a high yield, safety, low costs and environmental protection.
Synthesis and cytotoxic studies of novel 5-phenylisatin derivatives and their anti-migration and anti-angiogenic evaluation
Zhang, Qian,Teng, Yuou,Yuan, Yuan,Ruan, Tingting,Wang, Qi,Gao, Xing,Zhou, Yao,Han, Kailin,Yu, Peng,Lu, Kui
, p. 800 - 814 (2018/07/29)
A number of 5-arylisatin derivatives were synthesized in 5–6 steps from readily available starting materials. Their structures were confirmed by 1H NMR and 13C NMR as well as LC/MS. The cytotoxicity of these novel isatins against human leukemia K562 cells were evaluated by MTT assay in vitro. SAR studies indicated that the N-substituted benzyl and C-5 substituted phenyl groups greatly enhance their cytotoxic activity, whereas an intact carbonyl functionality on C-3 present in the parent ring is required to maintain such a potency. Particularly, N-(p-methoxybenzyl)-5-(p-methoxyphenyl)isatin (compound 2m) showed the highest antitumor activity against K562 cell lines (IC50 = 0.03 μM). Moreover, treatment with compound 2m significantly inhibited liver cancer HepG2 cells proliferation and migration, which could also reduce the human umbilical vein endothelial cells (HUVEC) tube formation. In conclusion, compound 2m exhibited very good cancer cells proliferation inhibition by angiogenesis responses in vitro, and 2m might be a promising angiogenesis inhibitor for cancer treatment.
An efficient synthesis of versatile synthon 3-chlorooxindoles with NaCl/oxone
Lakshmi Reddy, Vanammoole,Prathima, Parvathaneni Sai,Rao, Vaidya Jayathirtha,Bikshapathi, Raktani
, p. 20152 - 20155 (2018/12/13)
The present work describes an expedient approach for the direct conversion of indole-3-carboxaldehyde to 3-chlorooxindoles using a simple sustainable synthetic method. From an environmental perspective, a combination of NaCl/oxone in a CH3CN?:?H2O (1?:?1) system was developed for direct oxidative chlorination of a wide array of indole derivatives. This chlorination strategy is more viable, remarkably cheaper and provides easy access to potential 3-chlorooxindoles. In addition, this environmentally benign method can also be applicable for constructing isatin derivatives in good yields.
NaI-mediated divergent synthesis of isatins and isoindigoes: A new protocol enabled by an oxidation relay strategy
Zhang, Hong-Hua,Wang, Yong-Qiang,Huang, Long-Tao,Zhu, Long-Qing,Feng, Yi-Yue,Lu, Ying-Mei,Zhao, Quan-Yi,Wang, Xue-Qiang,Wang, Zhen
supporting information, p. 8265 - 8268 (2018/07/29)
A new approach for the synthesis of isatins and isoindigoes by an inexpensive and environmentally friendly NaI-mediated transformation is disclosed. The selectivity could be switched by simply varying the solvent, and isatins (using THF) and isoindigoes (using DMSO) could be obtained in moderate to excellent yields.
Synthesis of Indoline-2,3-diones by Radical Coupling of Indolin-2-ones with tert-Butyl Hydroperoxide
Ying, Wei-Wei,Zhu, Wen-Ming,Liang, Hongze,Wei, Wen-Ting
supporting information, p. 215 - 218 (2017/09/28)
A novel strategy has been developed for the synthesis of indoline-2,3-diones through a metal-free radical-coupling reaction. Alkyl radicals derived from indolin-2-ones through a radical-transfer reaction combine with the tert-butylhydroperoxy radical readily generated from commercially available tert-butyl hydroperoxide to afford 3-(tertbutylperoxy)indolin-2-one intermediates that can be further transformed into indoline-2,3-diones under air. This strategy provides a simple and e?cient route to the construction of a C=O bond without the use of any metal catalyst or base.
Oxindole-based intraocular pressure reducing agents
Zaryanova, Ekaterina V.,Lozinskaya, Nataly A.,Beznos, Olga V.,Volkova, Maria S.,Chesnokova, Nataly B.,Zefirov, Nikolay S.
supporting information, p. 3787 - 3793 (2017/07/27)
The study represents the new findings at the crossroads of chemistry and medicine, particularly between medicinal and organic chemistry and ophthalmology. In this work we describe how the chemical reactivity of indolinone scaffold may be used to create small molecule ligands with strong biological response comparable with and larger than that of endogenous hormone. The synthesis of oxindole-based melatonin and 5-methoxycarbonylamino-N-acetyltryptamine (5-MCA-NAT) analogues was proposed and their ability to influence intraocular pressure (IOP) was studied in vivo. Time-dependent study revealed the prolonged effect (more than 6?h) of the lead-compound. This effect in combination with high IOP reducing effect (41?±?6%) in low concentrations of the active compound (0.1?wt%) and with high water solubility represents a great potential of low-cost oxindole derivatives as potent antiglaucoma agents.
Assessment of 5-substituted Isatin as Surface Recognition Group: Design, Synthesis, and Antiproliferative Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors
Singh, Avineesh,Raghuwanshi, Kamlesh,Patel, Vijay K,Jain, Deepak K,Veerasamy, Ravichandran,Dixit, Anshuman,Rajak, Harish
, p. 366 - 374 (2017/09/27)
Histone deacetylase (HDAC) is a promising target for cancer treatment. HDAC inhibitors consist of three pharmacophoric features: an aromatic cap group, zinc binding group (ZBG), and a linker chain connecting cap group to ZBG. Herein, we report on (i) substituted isatin moiety as the cap group that recognizes the surface of active enzyme pocket and (ii) thiosemicarbazide moiety incorporated as linker group responsible for connecting the cap group to ZBG (hydroxamic acid). The synthesized compounds were evaluated for their antiproliferative activity and HDAC enzyme inhibition. The binding mode analysis of proposed compounds was evaluated by docking studies. Several analogs were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells, with GI50 values in the micromolar range. One compound (Vd) was found to have greater in vitro antiproliferative activity in comparison to other compounds.
