- Synthesis, antioxidant activity and SAR study of novel spiro-isatin-based Schiff bases
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Abstract: A new series of 21 Schiff bases of spiro-isatin was synthesized, and their DPPH, CUPRAC and ABTS cation radical scavenging abilities were investigated for antioxidant activity. The results showed that all the synthesized compounds exhibited anti
- Sonmez, Fatih,Gunesli, Zuhal,Kurt, Belma Zengin,Gazioglu, Isil,Avci, Davut,Kucukislamoglu, Mustafa
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Read Online
- Design, synthesis and biological evaluation of novel 1,5-disubstituted isatin derivatives as antitumor agents
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Isatin (1H-indole-2,3-dione) was reported to possess anticancer activities through its effect on tumor proliferation, apoptosis, and metastasis in vitro and in vivo. Here, we described the synthesis of a novel series of 1,5-disubstituted isatin derivative
- Zhuo, Huijun,Zhang, Zhen,Liu, Yang,Zhang, Jingya,Zhao, Guisen
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Read Online
- Discovery of Isatin-Based Carbohydrazones as Potential Dual Inhibitors of Fatty Acid Amide Hydrolase and Monoacylglycerol Lipase
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Using ligand-based design strategy, a set of isatin-3-carbohydrazones was designed, synthesized and evaluated for dual fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) inhibition properties. Compound 5-chloro-N′-(5-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 b) emerged as a potent MAGL inhibitor with nanomolar activity (IC50=3.33 nM), while compound 5-chloro-N′-(1-(4-fluorobenzyl)-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 j) was the most potent selective FAAH inhibitor (IC50=37 nM). Compound 5-chloro-N′-(6-chloro-2-oxoindolin-3-ylidene)-2-hydroxybenzohydrazide (13 c) showed dual FAAH-MAGL inhibitory activity with an IC50 of 31 and 29 nM respectively. Enzyme kinetics studies revealed that the isatin-based carbohydrazones are reversible inhibitors for both FAAH and MAGL. Further, blood-brain permeability assay confirmed that the lead compounds (13 b, 13 c, 13 g, 13 m and 13 q) are suitable as CNS candidates. Molecular dynamics simulation studies revealed the putative binding modes and key interactions of lead inhibitors within the enzyme active sites. The lead dual FAAH-MAGL inhibitor 13 c showed significant antioxidant activity and neuroprotection in the cell-based cytotoxicity assay. In summary, the study yielded three potent FAAH/MAGL inhibitor compounds (13 b, 13 c and 13 j) with acceptable pharmacokinetic profile and thus can be considered as promising candidates for treating neurological and mood disorders.
- Jaiswal, Shivani,Ayyannan, Senthil Raja
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- Microwave-Assisted Synthesis, Molecular Docking Studies and Biological Evaluation of Benzothiazole Containing Novel Indole Derivatives
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The synthesis of novel indole derivatives 4a-o using a microwave assisted method via Schiff’s base and Mannich base reaction mechanism was described. Compounds 3a-c were synthesized via reaction of 2-amino benzothiazole with substituted isatin by Schiff base reaction mechanism. Also, indole derivatives 4a-o were synthesized via reaction of compounds 3a-c with substituted benzaldehydes by Mannich base reaction. The biological potentials of the newly synthesized indole derivatives were evaluated for their anthelmintic activity and in vitro anticancer activity by MTT assay. The anticancer activity results suggested that indole derivatives 4c-o have activity against MCF-7 and SKOV3 cells in comparison with doxorubicin as standard drug. Furthermore, the molecular docking studies of these novel derivatives of indole showed good agreement with the biological results when their binding pattern and affinity towards the active site of EGFR was also investigated.
- Pandian, P.,Rajkamal, B.,Sultana, Shaheen
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p. 2755 - 2761
(2021/10/25)
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- Novel isatin derivative nitration method
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The invention belongs to the technical field of chemical pharmacy and fine chemical engineering preparation, and particularly discloses a novel isatin derivative nitration method. Trifluoroacetic acidis adopted to replace traditional sulfuric acid, so tha
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Paragraph 0023-0027
(2021/03/31)
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- Isoxazole formamido-4 (3H)-quinazolinone derivative as well as synthesis method and application thereof
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The invention relates to a 6-(isoxazolyl-3-formamido)-4 (3H)-quinazolinone derivative as well as a synthesis method and application thereof, belongs to the technical field of medicines, and relates to a general formula (I) in which R1, R2 and R3 are different substituent groups. The invention discloses structures and synthesis methods of the compounds, inhibitory activity of acetylcholin esterase and inhibitory activity of protein tyrosine phosphatase, and the compounds can be further developed into drugs for treating Alzheimer's disease.
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Paragraph 0020-0023
(2021/06/06)
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- 1-benzylisatin derivative as well as synthesis method and application thereof
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The invention relates to a 1-benzylisatin derivative as well as a synthesis method and application thereof, belongs to the technical field of medicines, and relates to a general formula (I) in which R1, R2 and R3 are different substituents. The invention discloses structures of the compounds, a synthesis method of the compounds, inhibitory activity of acetylcholin esterase and inhibitory activityof histone deacetylase 6; and the compounds can be further developed into drugs for treating Alzheimer's disease.
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Paragraph 0017-0018; 0023-0025
(2020/10/20)
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- Diketoindole compound containing urea structure as well as preparation method and application of diketoindole compound
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The invention relates to a diketoindole compound containing a urea structure as well as a preparation method and application of the diketoindole compound. The compound has a structure shown as a formula I in the specification. The invention also relates t
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Paragraph 0054-0058
(2021/01/11)
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- 2,3-diketone indole compound, preparation method and applications thereof
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The invention discloses a 2,3-diketone indole compound, a preparation method and applications thereof, wherein the compound has a structure represented by the following general formula (I) or (II). The invention further relates to a pharmaceutical composi
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Paragraph 0126-0128
(2020/02/10)
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- Synthesis and evaluation of isatin derivatives as antifungal agents
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Various types of isatin derivatives were synthesized by reacting isatin with different reagents viz substituted acetophenones, sodium nitrate, hydroxylamine hydrochloride and hydrazine hydrate. Characterization of the synthesized compounds was done by using various spectral techniques such as IR,1HNMR,13CNMR, elemental analysis and mass spectrometry. Synthesized compounds were further evaluated for their antifungal activity against Helminthosporium oryzae, Rhizoctonia solani and Fusarium moniliforme using poison food technique. 3-(2-Oxo-2-phenylethylidene) indolin-2-one showed significant mycelium inhibition against all tested rice fungi.
- Dawar, Monika,Kaur, Komalpreet,Rani, Ritu,Utreja, Divya
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p. 199 - 205
(2020/02/29)
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- Synthesis, anti-proliferative activity, theoretical and 1H NMR experimental studies of Morita–Baylis–Hillman adducts from isatin derivatives
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Abstract: Quaternary or spirocyclic 3-substituted-3-hydroxy-2-oxindole is considered a privileged scaffold. In other words, it is a molecular core present on several compounds with a wide spectrum of biological activities. Among its precursors, activated ketones (isatin nucleus) can be used as interesting starting points to Morita–Baylis–Hillman adducts derivatives, a class of compounds with good cytotoxic potential. In this paper, we present the synthesis, anti-proliferative activity against lung cancer cell line and a theoretical conformational study of 21 of Morita–Baylis–Hillman adducts from isatin derivatives, by DFT quantum chemical calculations, followed by a SAR and QSAR analysis. Besides, an efficient synthetic protocol and good biological activity profile were highlighted interesting observations about 1H NMR experimental spectra, molecular modeling results and crystallographic data available. Graphical abstract: [Figure not available: see fulltext.]
- Alencar-Filho, Edilson B.,Araújo, Edigenia C. C.,Brito, Vinicius B. M.,Lima-Júnior, Claudio G.,Martins, Felipe T.,Milit?o, Gardenia C. G.,Oliveira, Boaz G.,Santos, Gilmar F.,Silva, Fábio P. L.,Silva, Thiago D. S.,Souza, Júlia L. C.,Vasconcellos, Mário L. A. A.
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p. 265 - 281
(2019/09/16)
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- Design and synthesis of novel isatin derivatives as potent analgesic, anti-inflammatory and antimicrobial agents
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Abstract: A powerful analgesic, anti-inflammatory and antimicrobial drug was developed by synthesizing a set of new indole-2,3-dione derivatives. The chemical structures of the synthesized derivatives were confirmed by spectroscopic and elemental analyses
- Lahari, Kosaraju,Sundararajan, Raja
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- Synthesis and Cytotoxicity of Quinazolin-4(3H)-one Based Peptides
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Abstract: A novel series of quinazolin-4(3H)-one derivatives has been synthesized in high yields using the multicomponent Ugi reaction and characterized by IR, NMR and mass spectral data. The products have been tested for their cytotoxic activity against HeLa cells. Two tested compounds have shown potent activity compared to standard drug Doxorubicin. The in silico docking studies of the compounds against quinone reductase-2 (4ZVM) enzyme have also supported their activity.
- Bhavani, A. K. D.,Kumar, A. Kishore,Ramakrishna, K.,Shankaraiah, P.
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p. 720 - 724
(2020/07/02)
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- Organocatalytic Synthesis of Benzazetidines by Trapping Hemiaminals with Protecting Groups
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Benzazetidines are highly strained and inherently unstable heterocycles. There are only few methodologies for assembling these compounds. Here, a protocol is presented to trap an elusive cyclic, four-membered hemiaminal structure. This method affords several benzazetidines in moderate to good yields (up to 81%), and it uses inexpensive materials and does not require catalysts based on transition metals. The high ring strain energy of these benzazetidine systems was estimated by density functional theory calculations to be about 32 kcal mol-1. This synthesis can be applied also on gram scale with reaction yield essentially unchanged.
- Salvio, Riccardo,Placidi, Simone,Sinibaldi, Arianna,Di Sabato, Antonio,Buscemi, Dario C.,Rossi, Andrea,Antenucci, Achille,Malkov, Andrei,Bella, Marco
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p. 7395 - 7404
(2019/06/07)
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- Facile synthesis of isatins by direct oxidation of indoles and 3-iodoindoles using NIS/IBX
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A facile one-pot access to a broad range of isatins by direct oxidation of indoles using NIS/IBX reagent in DMSO at 25 °C in very good isolated yields is reported. It is shown by mechanistic investigations that a number of substituted indoles react rapidly with NIS in DMSO to produce intermediary 3-iodoindoles, which undergo oxidation subsequently to isatins with IBX.
- Chandra, Ajeet,Yadav, Navin R.,Moorthy, Jarugu Narasimha
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supporting information
p. 2169 - 2174
(2019/03/04)
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- Synthesis and Ameliorative Effect of Isatin–Mesalamine Conjugates on Acetic Acid-induced Colitis in Rats
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A series of new isatin–mesalamine conjugates (9a–g) were synthesized via conjugation of isatin (3a) and its derivatives (3b–3d, 4, 5, and 6) with mesalamine (7) by using chloroacetyl chloride as a bifunctional linker. Compounds 3a–3d were prepared by employing Sandmeyer reaction. Compounds 4, 5, and 6 were obtained from isatin (3a) via previously reported methods. The synthesized compounds were characterized by IR, mass, 1H NMR, and 13C NMR spectral techniques. Synthesized compounds (3a–d, 4, 5, 6, and 9a–g) were evaluated for in vitro antioxidant activity by DPPH assay method using ascorbic acid as standard. Hybrids 9b (IC50?=?368.6?±?3.5?μM) and 9f (IC50?=?335.1?±?2.9?μM) showed better antioxidant activity than its parent compounds such as 3a (IC50?=?556.8?±?2.9?μM), 5 (IC50?=?511.9?±?3.6?μM), and 7 (IC50?=?768.9?±?2.7?μM). Acetic acid-induced ulcerative colitis in rat model was chosen to examine the antioxidant potential of the synthesized hybrids (9b and 9f) in the amelioration of ulcerative colitis. Colonic myeloperoxidase and malondialdehyde enzymes were used as biomarkers of anti-ulcerative colitis activity. In the present study, hybrids 9b and 9f reduced the levels of colonic myeloperoxidase and malondialdehyde enzymes significantly (p??0.05) when compared with control (colitic), at a dose (0.03?mM/12.5?mg/kg b.w. p.o.) (50%) less than that of its parent moieties mesalamine (0.16?mM/25?mg/kg) and isatin (0.16?mM/25?mg/kg). Thus, the molecular hybridization was proved to be significant in enhancing the activity of hybrids 9b and 9f by reducing the dose.
- Panga, Shyam,Podila, Naveen Kumar,Ciddi, Veeresham
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p. 956 - 967
(2019/02/14)
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- Design, synthesis and biological evaluation of novel 2,3-indolinedione derivatives against mantle cell lymphoma
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2,3-Indolinedione derivatives have been identified as a novel class of promising agents for cancer treatment. In this study, eighteen 2,3-indolinedione derivatives were designed and synthesized, and their anticancer activities against mantle cell lymphoma (MCL) cells were evaluated. Most of them exhibited significant antiproliferative activity against the tested cell lines, and compound K5 was the most potent (MCL cellular IC50 = 0.4–0.7 μM). Further, compound K5 could induce cell apoptosis and cell cycle arrest in G2/M phase. Additionally, the results of drug-likeness analysis demonstrated that these novel 2,3-indolinedione derivatives could have potential as novel treatment strategies for MCL.
- Yu, Shengping,Liu, Yang,Zhang, Zhen,Zhang, Jingya,Zhao, Guisen
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p. 3319 - 3327
(2019/06/21)
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- A Facile Synthesis of Novel Isatinspirooxazine Derivatives and Potential in vitro Anti-Proliferative Activity
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Novel isatinspirooxazine derivatives were designed and synthesized as potential anti-proliferative agents. The new compounds were obtained from aldol condensation reactions between isatin and 3-(hydroxyimino)butan-2-one in the presence of an organic base in order to generate an aldol adduct, followed by cyclization in trifluoroacetic acid, providing the desired isatinspirooxazines in 30 to 80percent yield. All the synthesized compounds, including the starting material and the synthetic intermediates, were tested for in vitro anti-proliferative activity against cell lines MCF-7 and MDA-MB231 (breast cancer) and A549 (lung cancer), highlighting the compound 4-methyl,5'-methyl-spiro[(5-aza-4-eno-3-one-cyclohexane)-1,3'-(1H-indol-one)] with an IC50 (half maximal inhibitory concentration) = 0.34 μM, more potent than the reference drug, doxorubicin (IC50 = 1.88 μM), in breast cancer line MDA-MB231.
- Santos, Iara S.,Guerra, Fabiana S.,Bernardino, Lucas F.,Fernandes, Patrícia D.,Hamerski, Lidilhone,Silva, Bárbara V.
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p. 198 - 209
(2018/12/13)
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- Design, Synthesis, Characterization, and In Vitro Evaluation of Isatin-Pomalidomide Hybrids for Cytotoxicity against Multiple Myeloma Cell Lines
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Inspired by the concept of molecular hybridization, a series of new isatin-pomalidomide hybrids (9a–9g) were designed, synthesized, characterized, and evaluated for in vitro cytotoxic activity against U266B1 and RPMI 8226 multiple myeloma cell lines. Sandmeyer methodology and N-halomethylketo alkylation reaction are the two important reactions involved in the synthesis of isatin-pomalidomide hybrids (9a–9g). All the synthesized compounds (3a–3d, 4, 5, 6, and 9a–9g) were characterized by using IR, mass, 1H-NMR, and 13C-NMR spectral techniques. The efficacy of all the synthesized compounds was tested against the aforementioned cell lines by employing MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) standard protocols while using pomalidomide as a standard. The test concentrations used in the MTT assay were 1, 10, 20, 30, and 40?μM, and the period of incubation was 24?h. All the synthesized compounds were found to have moderate to greater cytotoxic activity against the aforementioned cell lines. Among them, synthesized hybrids 9f (IC50, U266B1?=?5.15?±?0.72?μM, RPMI8226?=?11.66?±?0.79?μM) and 9g (IC50, U266B1?=?2.50?±?0.37?μM, RPMI8226?=?6.70?±?0.55?μM) displayed better cytotoxic activity against both the cell lines used in the present study.
- Panga, Shyam,Podila, Naveen Kumar,Ciddi, Veeresham
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p. 2919 - 2928
(2018/10/26)
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- NaI-mediated divergent synthesis of isatins and isoindigoes: A new protocol enabled by an oxidation relay strategy
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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.
- 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
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supporting information
p. 8265 - 8268
(2018/07/29)
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- Synthesis of Indoline-2,3-diones by Radical Coupling of Indolin-2-ones with tert-Butyl Hydroperoxide
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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.
- Ying, Wei-Wei,Zhu, Wen-Ming,Liang, Hongze,Wei, Wen-Ting
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supporting information
p. 215 - 218
(2017/09/28)
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- Method for preparing indole-2,3-dione derivatives by catalytic oxidation of microwave copper/peroxyacetic acid
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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.
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Paragraph 0024; 0046
(2018/09/08)
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- Convenient and Clean Synthesis of Isatins by Metal-Free Oxidation of Oxindoles
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A metal-free synthesis of isatins was achieved through the oxidative reactions of oxindoles with molecular oxygen in the presence of tert -butyl nitrite as an additive. This strategy provides a convenient and simple synthetic route to the construction of C=O bonds without the need for any catalyst or base. The attractive features of this reaction include its convenient procedure and mild reaction conditions.
- Wei, Wen-Ting,Ying, Wei-Wei,Zhu, Wen-Ming,Wu, Yi,Huang, Yi-Ling,Cao, Yi-Qi,Wang, Yi-Ning,Liang, Hongze
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supporting information
p. 2307 - 2310
(2017/10/06)
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- Preparation method of indoledione compound
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The invention provides a preparation method of an indoledione compound. The method comprises the following steps: reacting an arylalkynyl compound of formula (I) with amine in an organic solvent in the presence of an oxidant, a catalyst and a ligand to obtain an acetaldehyde amide compound, and preparing the indoledione compound from the acetaldehyde amide under the action of hydrochloric acid. The method has the advantages of realization of high-yield synthesis of the indoledione compound, good application prospect and good industrial production potential.
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Paragraph 0036
(2017/08/30)
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- Assessment of 5-substituted Isatin as Surface Recognition Group: Design, Synthesis, and Antiproliferative Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors
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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.
- Singh, Avineesh,Raghuwanshi, Kamlesh,Patel, Vijay K,Jain, Deepak K,Veerasamy, Ravichandran,Dixit, Anshuman,Rajak, Harish
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p. 366 - 374
(2017/09/27)
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- Oxindole-based intraocular pressure reducing agents
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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.
- Zaryanova, Ekaterina V.,Lozinskaya, Nataly A.,Beznos, Olga V.,Volkova, Maria S.,Chesnokova, Nataly B.,Zefirov, Nikolay S.
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supporting information
p. 3787 - 3793
(2017/07/27)
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- New (E)-1-alkyl-1H-benzo[d]imidazol-2-yl)methylene)indolin-2-ones: Synthesis, in vitro cytotoxicity evaluation and apoptosis inducing studies
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A new series of (E)-benzo[d]imidazol-2-yl)methylene)indolin-2-one derivatives has been synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines of prostate (PC-3 and DU-145) and breast (BT-549, MDA-MB-231, MCF-7, 4T1), non-small lung (A549) and gastric (HGC) cancer cells along with normal breast epithelial cells (MCF10A). Among the tested compounds, 8l showed significant cytotoxic activity against MDA-MB-231 and 4T1 cancer cells with IC50values of 3.26 ± 0.24 μM and 5.96 ± 0.67 μM respectively. The compounds 8f, 8i, 8l and 8o were also screened on normal human breast epithelial cells (MCF10A) and found to be safer with lesser cytotoxicity. The treatment of MDA-MB-231 cells with 8l led to inhibition of cell migration ability through disruption of F-actin protein assembly. The flow-cytometry analysis reveals that the cells arrested in G0/G1 phase of the cell cycle. Further, the compound 8l induced apoptosis of MDA-MB-231 cells was characterized by different staining techniques such as Acridine Orange/Ethidium Bromide (AO/EB), DAPI, annexin V-FITC/PI, Rhodamine-123 and MitoSOX red assay. Western blot studies demonstrated that the compound 8l treatment led to activation of caspase-3, increased expression of cleaved PARP, increased expression of pro-apoptotic Bax and decreased expression of anti-apoptotic Bcl-2 in MDA-MB-231 cancer cells.
- Sharma, Pankaj,Thummuri, Dinesh,Reddy, T. Srinivasa,Senwar, Kishna Ram,Naidu,Srinivasulu, Gannoju,Bharghava, Suresh K.,Shankaraiah, Nagula
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p. 584 - 600
(2016/07/22)
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- Facile and efficient synthesis and biological evaluation of 4-anilinoquinazoline derivatives as EGFR inhibitors
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Series of 4-anilinoquinazoline derivatives were conveniently and efficiently synthesized and their antitumor activities were evaluated by MTT assay in three human cancer cell lines: H1975, HepG2 and SMMC-7721. New compounds 19a-19h were designed and synthesized to seek for powerful EGFR inhibitors and to explore whether methyl group at C-2 position of quinazoline ring has a positive effect on EGFR inhibition. All the compounds of 19a-19h were found potent against all three cell lines and five compounds (19c, 19d, and 19f-19h) were found more potent against H1975 than gefitinib. SAR studies revealed that methyl group at C-2 position of quinazoline ring could significantly improve the antitumor potency of 4-anilinoquinazolines. The same conclusion was also drawn according to the results of Western blotting analysis. Among all the tested compounds, 19g exhibited extremely potent against H1975 with an IC50 value of 0.11 μM, remarkably lower than that of gefitinib (1.23 μM). The results of western blotting analysis showed that compounds 19c and 19g could notably inhibit the expression of phosphorylated EGFR, especially 19g, almost inhibited completely.
- Wang, Zheng,Wu, Xue,Wang, Li,Zhang, Jiao,Liu, Jianli,Song, Zhongxing,Tang, Zhishu
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supporting information
p. 2589 - 2593
(2016/05/09)
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- 1,3-substituted-5-acetyl indole ketone compound, and its application in anti-tumour drug
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The invention relates to 1,3-substituted-5-acetaminoindolone compounds and an application thereof to anti-tumor drugs. The compounds are 1-methyl-5-acetamino-2-indolinone, 1-(4-bromobenzyl)-5-acetamino-2-indolinone, 1-(4-methylbenzyl)-3-oxime-5-acetaminoi
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Paragraph 0053-0054
(2016/11/24)
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- 6-amino-4(3H)-quinazolinone derivatives and their synthesis method and use
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The invention discloses 6-amino-4(3H)-quinazolinone derivatives and their synthesis method and use and belongs to the technical field of drug synthesis. The invention also relates to a use of the 6-amino-4(3H)-quinazolinone derivatives with a general formula (I) and its synthesis method in medical science, wherein in the general formula (I), X represents (CH2)n-1, n=1 to 10 and R1, R2 and R3 represent different substituents. The invention discloses the compound structures and their synthesis method and external acetylcholinesterase inhibition activity. The 6-amino-4(3H)-quinazolinone derivatives can be further studied and developed to form novel drugs for treating Alzheimer disease.
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Paragraph 0023; 0024
(2016/12/22)
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- Design, synthesis and preliminary biological evaluation of indoline-2,3-dione derivatives as novel HDAC inhibitors
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Histone deacetylases (HDACs) are zinc-dependent or NAD+ dependent enzymes and play a critical role in the process of tumor development. Herein a series of indoline-2,3-dione derivatives have been designed and synthesized as potential HDACs inhibitors. The preliminary biological evaluation showed that most compounds synthesized have exhibited moderate Hela cell nuclear extract inhibitory activities, among which compound 25a (IC50 = 10.13 nM) has shown the best efficacy. The anti-proliferative activities of some of these compounds were also discussed.
- Jin, Kang,Li, Shanshan,Li, Xiaoguang,Zhang, Jian,Xu, Wenfang,Li, Xuechen
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p. 4728 - 4736
(2015/08/03)
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- Synthesis of isatin derivatives under metal free conditions using hypervalent iodine
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Hypervalent iodine(III)/TEMPO-mediated C(sp3), C(sp2) C-H bond oxidation of different oxindole and indole derivatives to their corresponding isatin derivatives was successfully achieved with excellent yields at room temperature. This metal-free method provides a direct access to potential synthon isatin that could be applied in the total synthesis of several biologically active natural products.
- Sai Prathima, Parvathaneni,Bikshapathi, Raktani,Rao, Vaidya Jayathirtha
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p. 6385 - 6388
(2015/11/16)
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- Synthesis, Biological, and Computational Evaluation of Novel 1,3,5-Substituted Indolin-2-one Derivatives as Inhibitors of Src Tyrosine Kinase
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Several substituted indolin-2-one derivatives were synthesized and evaluated for their activities against Src kinase. Several compounds showed activity against Src, with IC50 values in the low micromolar range. Among them, compound 2f showed the most significant activity with an IC50 value of 1.02 μM. Molecular docking studies have been performed for evaluation of the binding modes of compound 2f into the Src active site. The docking structure of compound 2f disclosed that the indole NH forms a hydrogen bond with the carbonyl of Met341. These results suggest that our novel compound 2f is a promising compound for the further development of indole-based drugs targeting Src kinase. A novel series of indole-2-one derivatives were synthesized and evaluated for their Src inhibitory activities. Compound 2f was found as the most promising compound with an IC50 value of 1.02 μM. Molecular docking studies were performed to disclose the binding mode for compound 2f.
- Kilic-Kurt, Zühal,Bakar, Filiz,?lgen, Süreyya
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p. 715 - 729
(2015/10/12)
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- Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors
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The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CLpro. 3CLpro plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CL pro inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CLpro. Structure-activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k1 showed most potent inhibitory activity against 3CLpro (IC50 = 1.04 μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.
- Liu, Wei,Zhu, He-Min,Niu, Guo-Jun,Shi, En-Zhi,Chen, Jie,Sun, Bo,Chen, Wei-Qiang,Zhou, Hong-Gang,Yang, Cheng
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p. 292 - 302
(2014/01/17)
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- A novel strategy to the synthesis of 4-anilinoquinazoline derivatives
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A novel approach to prepare 4-anilinoquinazoline derivatives based on the transformation of indoline-2,3-dione to formamidine was developed. The processes with this approach are simple, efficient, and environmentally friendly. The efficiency of this approach was evaluated by synthesizing 17 4-anilinoquinazolines and comparing the obtained yields with those achievable through conventional synthetic methods. It was the first time that compounds 8d, 8e, 8h, and 13b-f were synthesized. The characteristics of the IR and the UV spectra of these compounds and the effects of their substituents on the spectra were observed.
- Wang, Zheng,Wang, Cuiling,Sun, Yanni,Zhang, Ning,Liu, Zhulan,Liu, Jianli
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p. 906 - 913
(2014/01/23)
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- Structure-based design, synthesis, andanticonvulsant activity of isatin-1-N-phenylacetamide derivatives
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In an effort to develop the potent anticonvulsant agents, a series of novel isatin-1-N-phenylacetamide derivatives was synthesized and screened for their in vivo anticonvulsant activity against maximal electroshock test and evaluated for their neurotoxicity by the rotarod test at the same dose levels. Ten compounds exhibited the anticonvulsant activity. 2-(5-Methyl-2,3-dioxoindolin-1- yl)-N-phenylacetamide (4b) was found to be the most potent compound of the series with an ED50 of 91.3 mg/kg, TD50 of >1,000 mg/kg, a higher protective index (PI = TD50/ED50, >11) was gained than the reference drug phenobarbital and carbamazepine. The essential structural features responsible for interaction with receptor site are established within a suggested pharmacophore. Springer Science+Business Media 2013.
- Xie, Chao,Tang, Li-Ming,Li, Fu-Nan,Guan, Li-Ping,Pan, Cheng-Yan,Wang, Si-Hong
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p. 2161 - 2168
(2014/05/06)
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- Novel 1-(4-substituted benzylidene)-4-(1-(substituted methyl)-2,3- dioxoindolin-5-yl)semicarbazide derivatives for use against Mycobacterium tuberculosis H37Rv (ATCC 27294) and MDR-TB strain
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A series of eighteen new 1-(4-substituted benzylidene)-4-(1-(substituted methyl)-2,3-dioxoindolin-5-yl)semicarbazide derivatives were designed, synthesized and characterized by spectral and elemental analyses. The derivatives were screened in vitro for an
- Raja, Sundararajan,Prakash, Chinnasamy Rajaram
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p. 411 - 422
(2013/07/19)
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- Synthesis of novel MT3 receptor ligands via an unusual Knoevenagel condensation
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New 5-acetamido-substituted melatonin derivatives were efficiently synthesized in excellent yields via Knoevenagel condensation. The relative binding affinity of new synthesized compounds to MT3 receptor was tested via enzymatic assays and the X-ray struc
- Volkova, Maria S.,Jensen, Katherine C.,Lozinskaya, Natalia A.,Sosonyuk, Sergey E.,Proskurnina, Marina V.,Mesecar, Andrew D.,Zefirov, Nikolay S.
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p. 7578 - 7581
(2013/02/22)
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- AlCl3/PCC-SiO2-promoted oxidation of azaindoles and indoles
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A simple and efficient method is described for the oxidation of 7-azaindoles and indoles to 7-azaisatins and isatins using pyridinium chlorochromate-silica gel (PCC-SiO2) with the aid of Lewis acid catalyst aluminium chloride (AlCl3) in dichloroethane. Simplicity of the reaction conditions, easy workup procedure, and good yields are the key features of this protocol.
- Sriram, Rekulapally,Sesha Sai Pavan Kumar, Chebolu Naga,Raghunandan, Nerella,Ramesh, Vadla,Sarangapani, Manda,Rao, Vaidya Jayathirtha
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experimental part
p. 3419 - 3428
(2012/09/22)
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- Design and synthesis of 4-(1-(4-chlorobenzyl)-2,3-dioxoindolin-5-yl)-1-(4- substituted/unsubstituted benzylidene) semicarbazide: Novel agents with analgesic, anti-inflammatory and ulcerogenic properties
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A new series of isatin semicarbazide derivatives (7a-7j) were synthesized and characterized by spectroscopic means and elemental analysis. Analgesic and anti-inflammatory screening was performed using tail-flick technique and the carrageenan-induced foot
- Prakash, Chinnasamy Rajaram,Raja, Sundararajan,Saravanan, Govindaraj
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scheme or table
p. 541 - 544
(2012/07/28)
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- Anticonvulsant Activity of Novel 1-(Substituted Benzylidene)-4-(1-(Morpholino/Piperidino Methyl)-2,3-Dioxoindolin-5-yl) Semicarbazide Derivatives in Mice and Rats Acute Seizure Models
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A series of novel 1-(substituted benzylidene)-4-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) semicarbazides 6a-6t was designed and synthesized on the basis of semicarbazide-based pharmacophoric model to meet the structural requirements necessa
- Prakash, Chinnasamy Rajaram,Raja, Sundararajan,Saravanan, Govindaraj
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p. 524 - 532
(2012/11/07)
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- Synthesis of novel triazol compounds containing isatin as potential antibacterial and antifungal agents by microwave and conventional methods
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Microwave irradiation has been used to accelerate the conversion of isatin (1a) and 5-nitroisatin (1b) into their Schiff bases 3-[5′-aryl(alkyl)- 2′,4′-dihydro-1′,2′,4′-triazol-3′-on- 4′-yl]iminoisatin (3a-g) and 3-[5′-aryl(alkyl)-2′,4′- dihydro-1′,2′,4′-triazol-3′-on-4′-yl] imino-5-nitroisatin (4a-g), respectively. Reaction was achieved by microwave-induced technique, which reduced the reaction time drastically and improved the yield when compared to conventional heating. The newly synthesised bases showed moderate antimicrobial activity against the standard bacterial and fungal organisms tested.
- Oezil, Musa,Mentese, Emre,Yilmaz, Fatih,Islamoglu, Fatih,Kahveci, Bahittin
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scheme or table
p. 268 - 271
(2011/10/05)
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- Design, synthesis and antiepileptic properties of novel 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl)urea derivatives
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Twenty new 1-(substituted benzylidene)-3-(1-(morpholino/piperidino methyl)-2,3-dioxoindolin-5-yl) urea derivatives were designed and synthesized. Antiepileptic screening was performed using MES and scPTZ seizures tests. The neurotoxicity was determined by
- Prakash, Chinnasamy Rajaram,Raja, Sundararajan
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experimental part
p. 6057 - 6065
(2012/01/06)
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- Synthesis and anticonvulsant properties of 1-(amino-N-arylmethanethio)-3- (1-substituted benzyl-2, 3-dioxoindolin-5-yl) urea derivatives
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Various 1-(amino-N-arylmethanethio)-3-(1-substituted benzyl-2, 3-dioxoindolin-5-yl) urea (5a-p) were designed keeping in view the structural requirements suggested in the pharmacophore model for anticonvulsant activity. Their in vivo anticonvulsant screenings were performed by two most adopted seizure models, maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ). Compound 5f was found active in MES screening while compounds 5h, 5i, 5k and 5l showed significant anticonvulsant activity in both the screenings and were devoid of any neurotoxicity. Compound 5h and 5i showed marked protection at 300 mg/kg against MES and scPTZ screening. Compound 5i also showed protection against MES screening at the dose of 100 mg/kg. In 6 Hz screening these two compounds showed significant protection and emerged as lead compounds for future investigations.
- Siddiqui, Nadeem,Alam, M. Shamsher,Stables, James P.
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experimental part
p. 2236 - 2242
(2011/06/21)
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- H-β zeolite: An efficient, reusable catalyst for one-pot synthesis of isatins from anilines
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We describe a simple and highly efficient procedure for the single-step preparation of isatins from the commercially available anilines using H-β zeolite as a truly heterogeneous catalyst. H-β zeolite is readily separated from reaction mixture by simple filtration and reused several times without considerable loss of activity.
- Victor Paul Raj,Shaikh, Tanveer Mahamadali,Sudalai, Arumugam
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experimental part
p. 466 - 469
(2010/08/07)
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- Use of pyridinium chlorochromate and reusable polyaniline salt catalyst combination for the oxidation of indoles
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A novel method is described herein for the simple, convenient and efficient oxidation of indoles to isatins using pyridinium chlorochromate with the aid of polyaniline salt catalyst at room temperature or at reflux in dichloroethane. Interestingly, oxidation of 3-alkyl indoles by this procedure gave 3-hydroxy 3-alkyl oxindoles. On the other hand, indol-3-alkanols gave mixtures of isatins and 3-formyl indoles. This is the first example of use of polyaniline as a catalyst in oxidation reaction.
- Kumar, Chebolu Naga Sesha Sai Pavan,Devi, Chebrolu Lavanya,Rao, Vaidya Jayathirtha,Palaniappan, Srinivasan
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scheme or table
p. 2023 - 2027
(2009/04/07)
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- Indium(III) chloride/2-iodoxybenzoic acid: A novel reagent system for the conversion of indoles into isatins
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Indoles and azaindoles undergo smooth oxidation with 2-iodoxybenzoic acid (IBX) in the presence of indium(III) chloride at 80°C to afford the corresponding isatins in excellent yields. This method is very useful for the direct preparation of isatins from indoles. The reaction proceeds smoothly in aqueous media and the products are obtained in excellent yields. Georg Thieme Verlag Stuttgart.
- Yadav,Subba Reddy,Reddy, Ch. Suresh,Krishna
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p. 693 - 696
(2007/12/29)
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- 5′-Phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2)
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5′-Phenyl-3′H-spiro[indoline-3,2′-[1,3,4]thiadiazol]-2-one inhibitors of ADAMTS-5 (Aggrecanase-2) have been prepared via commercially available starting materials. Selected compounds 23, 33-35 show sub-micromolar ADAMTS-5 potency and strong SAR trends with selectivity over the related metalloproteases ADAMTS-4 (Aggrecanase-1), MMP12, and MMP13. This series of compounds represents progress toward a selective ADAMTS-5 inhibitor as a disease modifying osteoarthritis drug.
- Bursavich, Matthew G.,Gilbert, Adam M.,Lombardi, Sabrina,Georgiadis, Katy E.,Reifenberg, Erica,Flannery, Carl R.,Morris, Elisabeth A.
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p. 5630 - 5633
(2008/03/14)
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- In vitro cytotoxicity evaluation of some substituted isatin derivatives
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A range of substituted 1H-indole-2,3-diones (isatins) were synthesized using standard procedures and their cytotoxicity evaluated against the human monocyte-like histiocytic lymphoma (U937) cell line in vitro. SAR studies identified C5, C6
- Vine, Kara L.,Locke, Julie M.,Ranson, Marie,Benkendorff, Kirsten,Pyne, Stephen G.,Bremner, John B.
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p. 931 - 938
(2007/10/03)
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- Study of some biorelevant complexes of manganese(II) with active imines
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Some new manganese(II) complexes of biologically relevant ligands, hydrazinecarboxamide and hydrazinecarbothioamide of 5-nitro-indol-2,3-dione and 6-nitro-indol-2,3-dione of the composition [MnCl(N∩X)H 2O] and [Mn(N∩X)2] have been isolated, where N ∩X = donor system of the ligand and X is oxygen or sulphur. The complexes have been characterized by the elemental analysis, molar conductance, magnetic measurements, molecular weight determinations, IR and ESR spectral studies. On the basis of spectroscopic studies, it has been inferred that the manganese(II) complexes are consistent with the tetrahedral geometry. The magnetic measurements reveal that the manganese(II) complexes are high spin in nature. All the ligands and their corresponding complexes have been screened for their antifungal and antibacterial activities.
- Garg, Rekha,Saini, Mahesh Kumar,Fahmi, Nighat,Singh
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p. 2433 - 2438
(2007/10/03)
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