608-05-9Relevant articles and documents
Study on synthesis of some substituted N-propargyl isatins by propargylation reaction of corresponding isatins using potassium carbonate as base under ultrasound- and microwave-assisted conditions
Tri, Nguyen Minh,Thanh, Nguyen Dinh,Ha, Luong Ngoc,Anh, Dang Thi Tuyet,Toan, Vu Ngoc,Giang, Nguyen Thi Kim
, p. 4793 - 4801 (2021/05/31)
Substituted N-propargyl isatins were synthesized by SN2 reaction of corresponding substituted isatins with propargyl bromide in the presence of anhydrous K2CO3 as base. We reported about study on systematically synthesis of these compounds using heating procedures under different reaction conditions, including microwave-assisted heating conditions at power of 100?W (Procedure A), conventional heating conditions in water bath at 50?°C in acetonitrile (Procedure B), and conventional heating conditions in water bath at 50?°C in DMF (procedure C). The best procedure A was deduced based on the investigations on the reaction conditions. Almost all substituted N-propargyl isatins were new, except compounds with R of H, 5-Me, 5-Cl and 5-Br substituents. The structures of the obtained compounds were confirmed by the modern spectroscopic methods.
Microwave-Assisted Synthesis, Molecular Docking Studies and Biological Evaluation of Benzothiazole Containing Novel Indole Derivatives
Pandian, P.,Rajkamal, B.,Sultana, Shaheen
, p. 2755 - 2761 (2021/10/25)
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.
Further Studies on Triazinoindoles as Potential Novel Multitarget-Directed Anti-Alzheimer's Agents
Patel, Dushyant V.,Patel, Nirav R.,Kanhed, Ashish M.,Teli, Divya M.,Patel, Kishan B.,Gandhi, Pallav M.,Patel, Sagar P.,Chaudhary, Bharat N.,Shah, Dharti B.,Prajapati, Navnit K.,Patel, Kirti V.,Yadav, Mange Ram
, p. 3557 - 3574 (2020/11/18)
The inadequate clinical efficacy of the present anti-Alzheimer's disease (AD) drugs and their low impact on the progression of Alzheimer's disease in patients have revised the research focus from single targets to multitarget-directed ligands. A novel series of substituted triazinoindole derivatives were obtained by introducing various substituents on the indole ring for the development of multitarget-directed ligands as anti-AD agents. The experimental data indicated that some of these compounds exhibited significant anti-AD properties. Among them, 8-(piperidin-1-yl)-N-(6-(pyrrolidin-1-yl)hexyl)-5H-[1,2,4]triazino[5,6-b]indol-3-amine (60), the most potent cholinesterase inhibitor (AChE, IC50 value of 0.32 μM; BuChE, IC50 value of 0.21 μM), was also found to possess significant self-mediated Aβ1-42 aggregation inhibitory activity (54% at 25 μM concentration). Additionally, compound 60 showed strong antioxidant activity. In the PAMPA assay, compound 60 exhibited blood-brain barrier penetrating ability. An acute toxicity study in rats demonstrated no sign of toxicity at doses up to 2000 mg/kg. Furthermore, compound 60 significantly restored the cognitive deficits in the scopolamine-induced mice model and Aβ1-42-induced rat model. In the in silico ADMET prediction studies, the compound satisfied all the parameters of CNS acting drugs. These results highlighted the potential of compound 60 to be a promising multitarget-directed ligand for the development of potential anti-AD drugs.
Bicyclic heteroaryl compound with PAR4 antagonistic activity and application thereof
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Paragraph 00740076; 0078, (2020/08/02)
The invention discloses a bicyclic heteroaryl compound with PAR4 antagonistic activity and application thereof. The invention provides the bicyclic heteroaryl compound with PAR4 antagonistic activity,and the bicyclic heteroaryl compound has remarkable antagonistic activity on PAR4 in an in-vitro anti-platelet aggregation experiment, so that platelet aggregation is effectively inhibited, and the bicyclic heteroaryl compound can be used for preparing medicines for preventing or treating various thromboembolic diseases.
Visible-Light-Mediated Dearomatisation of Indoles and Pyrroles to Pharmaceuticals and Pesticides
Schilling, Waldemar,Zhang, Yu,Riemer, Daniel,Das, Shoubhik
supporting information, p. 390 - 395 (2019/12/15)
Dearomatisation of indole derivatives to the corresponding isatin derivatives has been achieved with the aid of visible light and oxygen. It should be noted that isatin derivatives are highly important for the synthesis of pharmaceuticals and bioactive compounds. Notably, this chemistry works excellently with N-protected and protection-free indoles. Additionally, this methodology can also be applied to dearomatise pyrrole derivatives to generate cyclic imides in a single step. Later this methodology was applied for the synthesis of four pharmaceuticals and a pesticide called dianthalexin B. Detailed mechanistic studies revealed the actual role of oxygen and photocatalyst.
1-benzylisatin derivative as well as synthesis method and application thereof
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Paragraph 0052-0056, (2020/10/20)
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.
A rhodium(ii) catalysed domino synthesis of azepino fused diindoles from isatin tethered: N -sulfonyl-1,2,3-triazoles and indoles
Kahar, Nilesh,Jadhav, Pankaj,Reddy, R. V. Ramana,Dawande, Sudam
supporting information, p. 1207 - 1210 (2020/02/04)
An efficient and convenient protocol for the synthesis of a novel class of azepino fused diindoles from isatin tethered N-sulfonyl-1,2,3-triazoles and indoles has been disclosed. The reaction proceeds via denitrogenative aza-vinyl rhodium carbene formation to give a carbonyl ylide, which with indole results in 1,3-dipolar cycloaddition followed by sequential semipinacol rearrangement/ring expansion/oxidation to produce azepino fused diindoles. The reaction shows a broad substrate scope giving up to 81% yield. Furthermore, reversible catalytic hydrogenation and photophysical studies were carried out to demonstrate the application of these molecules.
Design and development of Isatin-triazole hydrazones as potential inhibitors of microtubule affinity-regulating kinase 4 for the therapeutic management of cell proliferation and metastasis
Aneja, Babita,Khan, Nashrah Sharif,Khan, Parvez,Queen, Aarfa,Hussain, Afzal,Rehman, Md. Tabish,Alajmi, Mohamed F.,El-Seedi, Hesham R.,Ali, Sher,Hassan, Md. Imtaiyaz,Abid, Mohammad
, p. 840 - 852 (2019/01/04)
Microtubule affinity-regulating kinase 4 (MARK4) is a potential drug target as the same is found to be over expressed in several types of cancers. In search of effective MARK4 inhibitors, we have synthesized and characterized Isatin-triazole hydrazones (9a-i) and evaluated their inhibitory potential. Of all the compounds, 9g showed better binding affinity and enzyme inhibition potential in sub micromolar range. Human serum albumin (HSA) binding assay suggested an easy transportation of 9g in blood stream due to its binding affinity. In vitro anticancer studies performed on MCF-7, MDA-MB-435s and HepG2 cells using 9g showed inhibition of cell proliferation and cell migration. Further, 9g induces apoptosis in these cancerous cells, with IC50 values of 6.22, 9.94 and 8.14 μM, respectively. Putatively, 9g seems to cause oxidative stress resulting in apoptosis. Functional assay of 9g with a panel of 26 kinases showed MARK4 specific profile. In conclusion, 9g seems to possess an effective inhibitory potential towards MARK4 adding an additional repertoire to anticancer therapeutics.
A Facile Synthesis of Novel Isatinspirooxazine Derivatives and Potential in vitro Anti-Proliferative Activity
Santos, Iara S.,Guerra, Fabiana S.,Bernardino, Lucas F.,Fernandes, Patrícia D.,Hamerski, Lidilhone,Silva, Bárbara V.
, p. 198 - 209 (2018/12/13)
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.
Facile synthesis of isatins by direct oxidation of indoles and 3-iodoindoles using NIS/IBX
Chandra, Ajeet,Yadav, Navin R.,Moorthy, Jarugu Narasimha
supporting information, p. 2169 - 2174 (2019/03/04)
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.
