50720-05-3Relevant articles and documents
Synthesis of phidianidines A and B
Lin, Hong-Yu,Snider, Barry B.
, p. 4832 - 4836 (2012)
Reaction of a substituted indole-3-acetyl chloride with N-5-azidopentyl-N′-hydroxyguanidine generated a substituted 3-(5-azidopentylamino)-5-((indol-3-yl)methyl)-1,2,4-oxadiazole. Reduction of the azide with zinc and ammonium formate afforded the amine, which was elaborated to the guanidine, completing short and efficient syntheses of the cytotoxic natural products phidianidines A and B in 19% overall yield by a convergent route that will make analogues readily available for biological evaluation. Initial screening in the NCI 60 cell line at 10-5 M indicated that the bromine on the indole is necessary for activity and that the amine precursor to phidianidine A is more potent than phidianidine A.
First practical and efficient synthesis of 3-phosphorylated β-carboline derivatives using the Pictet-Spengler reaction
Viveros-Ceballos, Jos Luis,Sayago, Francisco J.,Cativiela, Carlos,Ordez, Mario
, p. 1084 - 1091 (2015)
We report here the first practical and efficient synthesis of the diethyl 1,2,3,4-tetrahydro-β-carboline-3-phosphonates 3 and 4 as well as diethyl 9H-β-carboline-3-phosphonates 5 and 6. The target compounds were prepared in good yields by application of t
Concise total synthesis of phidianidine A and B
Buchanan, Jacob C.,Petersen, Brandon P.,Chamberland, Stephen
, p. 6002 - 6004 (2013)
The shortest total synthesis of cytotoxic indole alkaloids phidianidine A and B is described. Rapid assembly of the 1,2,4-oxadiazole core from a novel N-hydroxyguanidine and the corresponding indole-3-acetic acid chloride led to formal syntheses of phidianidine A and B in only three steps from known compounds. Deprotection under standard conditions provided the trifluoroacetate salts of phidianidine A and B in quantitative yield.
Synthesis of Novel N,N-Disubstituted Ethyl P-[2-(1 H-Indol-3-YL)Acetyl]Phosphoramidates and Their Biological Activity
Venkata Ramana,Madhava,Ravendra Babu,Subbarao,Hema Kumar,Naga Raju
, p. 2013 - 2022 (2015)
A series of novel N,N-disubstituted ethyl P-[2-(1H-indol-3-yl)acetyl]phosphoramid-ates were synthesized. All title compounds were characterized by IR, NMR (1H, 13C, 31P) spectra, mass spectra, and C, H, N analysis. The anticancer activity of the title compounds was evaluated in two human cell lines MCF-7 (breast cancer) and HeLa (Cervical cancer) cell lines by the use of the MTT assay, and the IC50 values were determined. The derivatives with substituted piperazines exhibited significant cytotoxicity against the tested cell lines at 5 μM and displayed low IC50 values in the region of 5.8-8.8 μM for MCF-7 cell lines and 14.8-16.4 μM for HeLa cell lines when compared with the standard doxorubicin (5.4 and 14.2 μM).
Observations arising from a Beckmann rearrangement-Mannich cyclization approach to the azepinobisindole alkaloid iheyamine A
Lindsay, Ashley C.,Sperry, Jonathan
, p. 4355 - 4362 (2017)
An overview of an iterative Beckmann rearrangement-Mannich cyclization approach to the azepinobisindole alkaloid iheyamine A is described. In a preliminary model study, the (E)-oxime 10 underwent Beckmann rearrangement to give the bisindolylacetamide 4 followed by an intramolecular Mannich cyclization affording 2-(indolin-2-yl)indole 5 containing the heterocyclic framework of the iheyamine alkaloids. However, the 2-(indolin-2-yl)indole 5 could not be converted into the azepinobisindole core of iheyamine A. When the same Beckmann-Mannich approach was applied toward the natural product itself, a result was obtained that contrasted the model study. The (E)-oxime 3 did not undergo Beckmann rearrangement, but instead an intramolecular Mannich cyclization whereby the electron rich C4 site attacked the intermediate iminum ion, generating the 4-(indolin-2-yl)indole 25 bearing the heterocyclic framework of the slime mould pigment arcyriacyanin A. Although this route did not result in the synthesis of iheyamine A being accomplished, some interesting observations related to the venerable Beckmann rearrangement and Mannich cyclization reactions are described.
Design, synthesis, and antitumor activity of novel benzoheterocycle derivatives as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase
Ding, Yangyang,Liu, Kai,Zhao, Xinyu,Lv, Yingtao,Yu, Rilei,Kang, Congmin
, p. 286 - 294 (2020/01/28)
The vascular endothelial growth factor receptor-2 signaling pathway promotes the formation of new blood vessels, and vascular endothelial growth factor receptor-2 tyrosine kinase exists in both active and inactive conformations. Novel indole–benzimidazole and indole–benzothiazole derivatives joined by different linkers are designed and synthesized as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. All the synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines (HeLa, HT29, A549, and MDA-MB-435) and human umbilical vein endothelial cell. Meanwhile, the inhibitory activities against vascular endothelial growth factor receptor-2 are estimated in vitro and the binding interactions with dual conformations of vascular endothelial growth factor receptor-2 tyrosine kinase are evaluated by molecular docking. Compounds 5a–c and 14 show inhibitory activity against vascular endothelial growth factor receptor-2 tyrosine kinase and promising cytotoxicity, specifically with IC50 values ranging between 0.1 and 1 μM, which imply broad-spectrum antitumor activity. These results provide a deep insight into potential structural modifications for developing potent vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.
Development of [18F]Maleimide-Based Glycogen Synthase Kinase-3β Ligands for Positron Emission Tomography Imaging
Hu, Kongzhen,Patnaik, Debasis,Collier, Thomas Lee,Lee, Katarzyna N.,Gao, Han,Swoyer, Matthew R.,Rotstein, Benjamin H.,Krishnan, Hema S.,Liang, Steven H.,Wang, Jin,Yan, Zhiqiang,Hooker, Jacob M.,Vasdev, Neil,Haggarty, Stephen J.,Ngai, Ming-Yu
supporting information, p. 287 - 292 (2017/03/17)
Dysregulation of glycogen synthase kinase-3β (GSK-3β) is implicated in the pathogenesis of neurodegenerative and psychiatric disorders. Thus, development of GSK-3β radiotracers for positron emission tomography (PET) imaging is of paramount importance, because such a noninvasive imaging technique would allow better understanding of the link between the activity of GSK-3β and central nervous system disorders in living organisms, and it would enable early detection of the enzyme’s aberrant activity. Herein, we report the synthesis and biological evaluation of a series of fluorine-substituted maleimide derivatives that are high-affinity GSK-3β inhibitors. Radiosynthesis of a potential GSK-3β tracer [18F]10a is achieved. Preliminary in vivo PET imaging studies in rodents show moderate brain uptake, although no saturable binding was observed in the brain. Further refinement of the lead scaffold to develop potent [18F]-labeled GSK-3 radiotracers for PET imaging of the central nervous system is warranted.
Use of indole compounds in radix isatidis, and derivatives thereof in preparation of anti-influenza virus medicines
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Paragraph 0514; 0516, (2017/09/21)
The invention discloses an application of indole compounds extracted from radix isatidis and represented by general formula (I), and derivatives and pharmaceutically acceptable salts thereof in the preparation of anti-influenza virus medicines or healthcare products, and discloses a preparation method of the compounds, and an application of medicinal compositions containing the compounds in the preparation of the anti-influenza virus medicines or healthcare products.
Indole compound with antivirus activity in radix isatidis and derivative of indole compound
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Paragraph 0516, (2017/09/29)
The invention discloses an indole compound extracted from radix isatidis shown in a general formula (I) and a derivative of the indole compound, as well as a salt acceptable on pharmacy, a preparation method of the compound, and a medicinal composite. The compound has apparent HIV-resisting activity and influenza virus-resisting activity, and can be used for preparing drugs or healthcare products for resisting HIV or influenza viruses. (The formula is shown in the description.).
Design, synthesis and activity evaluation of some novel indole derivatives
He, Dian,Yang, Zhu-Qing,Hou, Meng
, p. 1729 - 1734 (2015/03/04)
A series of novel indole derivatives as CDK4 inhibitors were designed and synthesized though the condensation reaction between the indolic acid and the corresponding substituted amine. The key step of our synthetic process is the efficient condensation reaction conducted by two different methods. The MTT and kinase assays were conducted used to assess the antitumor activity and cyclin-dependent kinases (CDKs) inhibitory activity. The most active compound 8b has an IC50 of 10-25 μM for the inhibition of four different tumor cells and CDK4. The higher activities of 8b were influenced by more conformational freedom resulted form the non-planar structure and by the stronger hydrogen bonding capability. Thus, the strategy we adapt to design potent, non-toxic CDK4 inhibitors is successful.
