- Novel spiro and fused heterocycles from the allylation of indigo
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The allylation of indigo results in the one-step synthesis of two unique complex heterocyclic systems: a spiroindoline-pyridoindolone arising from the addition of three allyl moieties and a fused pyridoindolo-azepinoindolone generated from the addition and subsequent cyclisation of two allyl moieties. The structures of these novel heterocycles are assigned unambiguously using extensive NMR experiments and by X-ray crystallographic analysis. The distribution of the products is influenced by the use of thermal versus microwave heating. Crown Copyright
- Abdel-Hamid, Mohammed K.,Bremner, John B.,Coates, Jonathan,Keller, Paul A.,Mil?nder, Celia,Torkamani, Yasmine S.,Skelton, Brian W.,White, Allan H.,Willis, Anthony C.
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- 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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- Rongalite-induced transition-metal and hydride-free reductive aldol reaction: a rapid access to 3,3′-disubstituted oxindoles and its mechanistic studies
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A transition-metal and hydride-free reductive aldol reaction has been developed for the synthesis of biologically active 3,3′-disubstituted oxindoles from isatin derivatives using rongalite. In this protocol, rongalite plays a dual role as a hydride-free
- Anugu, Naveenkumar,Golla, Sivaparwathi,Jalagam, Swathi,Kokatla, Hari Prasad
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p. 808 - 816
(2022/02/03)
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- Photoenolization/nucleophilic addition enables direct access to 3-alkyl-3-hydroxy-indolin-2-ones
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A light-driven, catalyst- and additive-free photoenolization/nucleophilic addition reaction for the synthesis of 3-benzyl-3-hydroxyindolin-2-ones is presented. In this reaction, 2-methylbenzophenones undergo light-induced enolization process to afford hydroxy-o-quinodimethanes (hydroxy-o-QDMs), which are then immediately captured by the electrophilic isatins. The reaction utilizes green and clean light energy to realize the C–H activation of the inert benzyl position of 2-methylbenzophenones. This method tolerates a wide scope of substrates and provides concise access to a series of novel 3-benzyl-3-hydroxyindolin-2-ones with 60–99% yields.
- Guan, Zhi,He, Yan-Hong,Tang, Li,Wang, Zhi-Lv,Zeng, Wei-Mei
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supporting information
(2022/03/27)
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- Organocatalytic Asymmetric Synthesis of Cyclic Acetals with Spirooxindole Skeleton
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An organocatalytic asymmetric synthesis of cyclic acetal with spirooxindole skeleton has been developed via a domino reaction between isatin and γ-hydroxy enones. Bifunctional squaramide catalyst with adamantyl motif was found to be the most effective for the cascade reaction. With 10 mol% of the catalyst, the desired products were obtained in 1.8:1 to 9:1 diastereo- and 86% to >99% enantioselectivities from a range of substituted isatins and γ-hydroxy enones. (Figure presented.).
- Shikari, Amit,Mandal, Koushik,Chopra, Deepak,Pan, Subhas Chandra
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supporting information
p. 58 - 63
(2021/11/09)
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- Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations
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In the current medical era, human health is experiencing numerous challenges, particularly the human malignancies. Therefore, the therapeutic arsenal for these malignancies is to be inexorably enhanced with new treatments that target tumor cells in a selective manner. In this regard, the present work aims at developing a new set of small molecules featuring the privileged isatin scaffold conjugated with a thiazolo[3,2-a]benzimidazole (TBI) motif through a cleavable hydrazide linker (7a-e and 10a-i) as potential anticancer CDK2 inhibitors. The large tricyclic TBI motif is anticipated to achieve a plethora of hydrophobic interactions within the CDK2 binding site. The growth of the two examined cell lines was significantly inhibited by most the prepared hybrids with IC50 ranges; (2.60 ± 1.47–20.90 ± 1.17 μM, against MDA-MB-231) and (1.27 ± 0.06–16.83 ± 0.95 μM, against MCF-7). In particular, hybrids 7a, 7d and 10a displayed potent dual activity against the examined cell lines, and thus selected for further investigations. They exerted a significance alteration in the cell cycle progression, in addition to an apoptosis induction within both MDA-MB-231 and MCF-7 cells. Furthermore, 7a, 7d and 10a displayed potent CDK2 inhibitory action (IC50 = 96.46 ± 5.3, 26.24 ± 1.4 and 42.95 ± 2.3 nM, respectively). The docking simulations unveiled, as expected, the ability of the TBI ring to well-accommodate and establish several hydrophobic interactions within a hydrophobic pocket in the CDK2 binding site. Also, the docking simulations highlighted the significance of incorporation of the hydrazide linker and isatin unsubstituted (NH) functionality in the H-bonding interactions. Interestingly, the most potent CDK2 inhibitor 7d achieved the best binding score (-11.2 Kcal/mole) and formed the most stable complex with CDK2 enzyme (RMSD = 1.24 ?) in a 100 ns MD simulation. In addition, the MM-PBSA calculations ascribed the lowest binding free energy to the 7d–CDK2 complex (?323.69 ± 15.17 kJ/mol). This could be attributed to an incorporation of the 5-OCH3 group that was engaged in an extra hydrogen bonding with key THR14 amino acid residue. Finally, these results suggested hybrid 7d as a good candidate for further optimization as promising breast cancer antitumor agent and CDK2 inhibitor.
- Eldehna, Wagdy M.,El Hassab, Mahmoud A.,Abo-Ashour, Mahmoud F.,Al-Warhi, Tarfah,Elaasser, Mahmoud M.,Safwat, Nesreen A.,Suliman, Howayda,Ahmed, Marwa F.,Al-Rashood, Sara T.,Abdel-Aziz, Hatem A.,El-Haggar, Radwan
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supporting information
(2021/03/15)
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- Applications of Ytterbium(II) Reagent as Grignard Reagent and Single-Electron Transfer Reagent in the Synthesis of 3-Substituted 2-Oxindoles
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The use of ytterbium(II) reagent as both nucleophilic reagent and single-electron transfer reagent in the reaction of isatin derivatives with ytterbium(II) reagent is reported. From a synthetic point of view, a general, efficient, and experimentally simple one-pot method for the preparation of 3-substituted 2-oxindoles was developed.
- Wang, Pengkai,Cao, Xuyan,Zhang, Songlin
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supporting information
p. 3836 - 3846
(2021/07/02)
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- Microwave-assisted synthesis and antimicrobial activity of novel spiro 1,3,4-thiadiazolines from isatin derivatives
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This work describes the synthesis of spiro 1,3,4-thiadiazolines from isatin-β-thiosemicarbazone acetylation, using microwave irradiation as a source of heating the reaction medium. N-substituted isatin derivatives were used as substrates to obtain thiosemicarbazones by adding thiosemicarbazide to the isatin ketone carbonyl. The final synthetic step was the reaction of thiosemicarbazones with acetic anhydride under microwave irradiation to get the spiro compounds. Reaction times ranged from 6 to 18 minutes resulting in yields of up to 90%. Biological assays have shown promising antibacterial and antifungal activity, especially spiro thiadiazolines derived from allylated isatins. All the proposed molecules proved to be potential drug candidates based on the results of the in silico investigation, with satisfactory drug-likeness and drug-score, respecting Lipinski's rule. The use of the microwave reactor was efficient for the synthesis of thiosemicarbazones and spiro compounds, resulting in a significant reduction in reaction times with conventional heating. Taking into account the threat of antimicrobial resistance, this work presents a series of bioactive molecules that are easily obtained via microwave reaction.
- da Costa, Daniel Pereira,de Castro, Aleff Cruz,da Silva, Girlyanderson Araújo,Lima-Junior, Claudio Gabriel,de Andrade Júnior, Francisco Patricio,de Oliveira Lima, Edeltrudes,Vaz, Boniek Gontijo,da Silva, Lidya Cardoso
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p. 766 - 776
(2020/12/31)
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- Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: design, synthesis, biological evaluation, and in silico studies
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The serine/threonine protein kinases CDK2 and GSK-3β are key oncotargets in breast cancer cell lines, therefore, in the present study three series of oxindole-benzofuran hybrids were designed and synthesised as dual CDK2/GSK-3β inhibitors targeting breast cancer (5a–g, 7a–h, and 13a–b). The N1 -unsubstituted oxindole derivatives, series 5, showed moderate to potent activity on both MCF-7 and T-47D breast cancer cell lines. Compounds 5d–f showed the most potent cytotoxic activity with IC50 of 3.41, 3.45 and 2.27 μM, respectively, on MCF-7 and of 3.82, 4.53 and 7.80 μM, respectively, on T-47D cell lines, in comparison to the used reference standard (staurosporine) IC50 of 4.81 and 4.34 μM, respectively. On the other hand, the N1 -substituted oxindole derivatives, series 7 and 13, showed moderate to weak cytotoxic activity on both breast cancer cell lines. CDK2 and GSK-3β enzyme inhibition assay of series 5 revealed that compounds 5d and 5f are showing potent dual CDK2/GSK-3β inhibitory activity with IC50 of 37.77 and 52.75 nM, respectively, on CDK2 and 32.09 and 40.13 nM, respectively, on GSK-3β. The most potent compounds 5d–f caused cell cycle arrest in the G2/M phase in MCF-7 cells inducing cell apoptosis because of the CDK2/GSK-3β inhibition. Molecular docking studies showed that the newly synthesised N1 -unsubstituted oxindole hybrids have comparable binding patterns in both CDK2 and GSK-3β. The oxindole ring is accommodated in the hinge region interacting through hydrogen bonding with the backbone CO and NH of the key amino acids Glu81 and Leu83, respectively, in CDK2 and Asp133 and Val135, respectively, in GSK-3β. Whereas, in series 7 and 13, the N1 -substitutions on the oxindole nucleus hinder the compounds from achieving these key interactions with hinge region amino acids what rationalises their moderate to low anti-proliferative activity.
- Eldehna, Wagdy M.,Al-Rashood, Sara T.,Al-Warhi, Tarfah,Eskandrani, Razan O.,Alharbi, Amal,El Kerdawy, Ahmed M.
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p. 270 - 285
(2020/12/18)
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- Direct catalytic synthesis of β-(C3)-substituted pyrroles: A complementary addition to the Paal-Knorr reaction
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The synthesis of β-(C3)-functionalized pyrroles is a challenging task and requires a multistep protocol. An operationally simple direct catalytic synthesis of β-substituted pyrroles has been developed. This one-pot multicomponent method combined aqueous succinaldehyde as 1,4-dicarbonyl, primary amines, and isatins to access hydroxyl-oxindole β-tethered pyrroles. Direct synthesis of the β-substituted free NH-pyrrole is the central intensity of this work. DFT-calculations and preliminary mechanism investigation support the possible reaction pathway. This journal is
- Pawar, Amol Prakash,Yadav, Jyothi,Mir, Nisar Ahmad,Iype, Eldhose,Rangan, Krishnan,Anthal, Sumati,Kant, Rajni,Kumar, Indresh
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supporting information
p. 251 - 254
(2021/01/13)
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- Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3′-Spiro[β-lactam]-oxindoles
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Oxindoles and β-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3′-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides. With this protocol, a collection of 3,3-spiro[β-lactam]-oxindoles were facilely produced in up to 94% yield with perfect diastereoselectivity.
- Leng, Hai-Jun,Li, Qing-Zhu,Xiang, Peng,Qi, Ting,Dai, Qing-Song,Jia, Zhi-Qiang,Gou, Chuan,Zhang, Xiang,Li, Jun-Long
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supporting information
p. 1451 - 1456
(2021/03/08)
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- Organocatalytic Enantioselective Synthesis of Tetrahydro-Furanyl Spirooxindoles via [3+2] Annulations of 3-Hydroxyoxindoles and Cyclic Ketolactams
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Asymmetric construction of pharmacologically interesting tetrahydrofuranyl spirooxindole frameworks has been achieved through organocatalytic [3+2] annulations of the readily available 3-hydroxyoxindoles and pyrrolidone-derived cyclic ketolactams. A variety of chiral spiro tetrahydrofuranyl products, which contain four contiguous stereocenters including two tetrasubstituted carbon centers, have been rapidly synthesized with remarkable results (up to 99% yield, >95:5 dr, and 99:1 er). Synthetic derivatization of the hemiketal moiety enables the installation of various halogen atoms into the structurally complex molecules in a stereospecific manner. Preliminary screening of anticancer bioactivity was performed, and 4 w showed obvious inhibitory capacity to the proliferation on a panel of cancer cell lines. (Figure presented.).
- Liu, Yue,Zhang, Ying,Huang, Qian-Wei,Gou, Chuan,Li, Qing-Zhu,Dai, Qing-Song,Leng, Hai-Jun,Li, Jun-Long
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supporting information
p. 2177 - 2182
(2021/03/08)
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- Palladium catalyzed divergent cycloadditions of vinylidenecyclopropane-diesters with methyleneindolinones enabled by zwitterionic π-propargyl palladium species
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A palladium-catalyzed divergent synthesis of spirooxindoles fused with a five- or a six-membered ring by a cycloaddition reaction of vinylidenecyclopropane-diesters with methyleneindolinones was disclosed. This protocol features anin situgenerated unprecedented zwitterionic π-propargyl palladium species in cycloaddition reactions and a switchable process between (3+2) and (4+2) cycloadditions by changing the phosphine ligand.
- Niu, Ben,Wei, Yin,Shi, Min
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supporting information
p. 4783 - 4786
(2021/05/25)
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- Development of novel benzofuran-isatin conjugates as potential antiproliferative agents with apoptosis inducing mechanism in Colon cancer
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In the current work, a new set of carbohydrazide linked benzofuran-isatin conjugates (5a–e and 7a–i) was designed and synthesised. The anticancer activity for compounds (5b–d, 7a, 7b, 7d and 7g) was measured against NCI-55 human cancer cell lines. Compound 5d was the most efficient, and thus subjected to the five-dose screen where it showed excellent broad activity against almost all tested cancer subpanels. Furthermore, all conjugates (5a–e and 7a–i) showed a good anti-proliferative activity towards colorectal cancer SW-620 and HT-29 cell lines, with an excellent inhibitory effect for compounds 5a and 5d (IC50 = 8.7 and 9.4 μM (5a), and 6.5 and 9.8 μM for (5d), respectively). Both compounds displayed selective cytotoxicity with good safety profile. In addition, both compounds provoked apoptosis in a dose dependent manner in SW-620 cells. Also, they significantly inhibited the anti-apoptotic Bcl2 protein expression and increased the cleaved PARP level that resulted in SW-620 cells apoptosis.
- Eldehna, Wagdy M.,Salem, Rofaida,Elsayed, Zainab M.,Al-Warhi, Tarfah,Knany, Hamada R.,Ayyad, Rezk R.,Traiki, Thamer Bin,Abdulla, Maha-Hamadien,Ahmad, Rehan,Abdel-Aziz, Hatem A.,El-Haggar, Radwan
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p. 1424 - 1435
(2021/07/02)
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- Lanthanide Silylamide-Catalyzed Synthesis of Pyrano[2,3- b]indol-2-ones
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A lanthanide silylamide-catalyzed tandem reaction of isatins, diethyl phosphite, and 2,3-diarylcyclopropenones has been developed. A series of pyrano[2,3-b]indol-2-ones were synthesized in high yields. The cooperation of the Lewis acidity of the lanthanide center and the Bronsted basicity of the N(SiMe3)2 anion may be the key factor affecting the catalytic activity of lanthanide amides.
- Chen, Qifa,Teng, Yue,Xu, Fan
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supporting information
p. 4785 - 4790
(2021/06/28)
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- Catalytic Asymmetric Addition of Diorganozinc Reagents to Pyrazole-4,5-Diones and Indoline-2,3-Diones
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The catalytic enantioselective diorganozinc additions to cyclic diketones including pyrazolin-4,5-diones and isatins have been developed. In the presence of morpholine-containing chiral amino alcohol ligand, the corresponding chiral cyclic tertiary alcohols were produced in good to excellent yields (up to 97 %) and enantioselectivities (up to 95 % ee). The notable feature of this protocol includes its mild reaction conditions, Lewis acid additives free and broad functional group tolerance.
- Wang, Rong-Hui,Li, Ya-Ling,He, Hong-Jiao,Xiao, You-Cai,Chen, Fen-Er
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supporting information
p. 4302 - 4306
(2021/02/16)
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- Dynamic Kinetic Asymmetric Transformation of Racemic Diastereomers: Diastereo- and Enantioconvergent Michael–Henry Reactions to Afford Spirooxindoles Bearing Furan-Fused Rings
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Dynamic kinetic asymmetric transformation (DYKAT) reactions of racemic diastereomer mixtures that afford the products as essentially single diastereomers with high enantioselectivities are described. We demonstrated the DYKAT in the diastereo- and enantio
- Sohail, Muhammad,Tanaka, Fujie
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supporting information
p. 21256 - 21260
(2021/08/23)
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- Organocatalytic Asymmetric Synthesis of Aza-Spirooxindoles via Michael/Friedel-Crafts Cascade Reaction of 1,3-Nitroenynes and 3-Pyrrolyloxindoles
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An asymmetric [3+3] cyclization of nitroenynes and 3-pyrrolyloxindoles has been realized with a chiral bifunctional squaramide catalyst. This Michael/Friedel-Crafts cascade strategy provides a facile and efficient access to enantioenriched polycyclic aza-spirooxindoles with 32-95% isolated yields and excellent stereocontrol under mild reaction conditions.
- Ni, Qijian,Wang, Xuyang,Zeng, Da,Wu, Qianling,Song, Xiaoxiao
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supporting information
p. 2273 - 2278
(2021/04/05)
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- The selective condensation of pyrazolones to isatins in aqueous medium
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The selective condensation of pyrazolones with isatins using water as the reaction medium is presented. This strategy provides an environmentally benign synthetic route to synthesize various potentially bioactive pyrazolone substituted oxindoles.
- Zhang, Yong,Nie, Long-Jun,Luo, Liang,Mao, Jia-Xin,Liu, Jin-Xiang,Xu, Guo-Hai,Chen, Deliang,Luo, Hai-Qing
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supporting information
(2020/01/08)
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- Synthesis, structural properties, enzyme inhibition and molecular docking studies of (Z)-N'-(1-allyl-2-oxoindolin-3-ylidene) methanesulfono-hydrazide and (Z)-N'-(1-allyl-2-oxoindolin-3-ylidene)-3-nitrobenzenesulfono-hydrazide
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Isatin and its derivatives exhibit broad range of biological and pharmacological applications. Keeping in view the importance of isatin and its derivatives, herein we report two isatin based new sulfono-hydrazides 4 & 5, synthesized in high yields and characterized by spectroscopic techniques. Their structures are confirmed unequivocally using X-ray diffraction crystallography, which revealed the presence of P21/c (4) and P21/n (5) space groups and unit cells stabilized through noncovalent interactions. Further details about geometric and electronic properties of compounds 4 and 5 are obtained by quantum mechanical approach based on density functional theory (DFT). These compounds are also evaluated for in vitro urease enzyme inhibition potential against Bacillus pasteurii. Both compounds inhibited the urease activity in μM concentration, however, compound 4 with IC50 value of 15.26 ± 0.16 μM proved to be more potent than the standard thiourea having IC50 value of 21.25 ± 0.15 μM. The higher inhibition activity of compound 4 might be associated with its stronger interaction as observed by in silico molecular docking studies using MOE, which showed that compound 4 interacts more closely to the binding site of enzyme (4UBP) via Ni2+ ions coordination as compared to its counterpart.
- Ahmed, Kainat,Arshad, Muhammad,Arshad, Muhammad Nadeem,Asiri, Abdullah M.,Iqbal, Zafar,Mahmood, Tariq,Rashid, Umer
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- Reductive aromatization of oxindoles to 3-substituted indoles
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A practical and scalable approach for the synthesis of 3-substituted indoles is delineated via hydride nucleophilic addition to 3-substituted-2-oxindoles. The reaction proceeds through reductive aromatization involving indolinium ion intermediate. A wide range of 3-functionalized indoles have been synthesized. The method is employed for the synthesis of 3,3?-bis-indoles and a dimeric 3-indole derivative. Moreover, this protocol is used to obtain naturally occuring amino acid tryptamine.
- Mandal, Tirtha,Chakraborti, Gargi,Dash, Jyotirmayee
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supporting information
(2020/06/21)
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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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- Candida antarctica lipase-B-catalyzed kinetic resolution of 1,3-dialkyl-3-hydroxymethyl oxindoles
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Candida antarctica (CAL-B) lipase-catalyzed resolution of 1,3-dialkyl-3-hydroxymethyl oxindoles has been performed to obtain (R)-1,3-dialkyl-3-acetoxymethyl oxindoles with up to 99% ee and (S)-1,3-dialkyl-3-hydroxymethyl oxindoles with up to 78% ee using vinyl acetate as acylating agent and acetonitrile as solvent transforming (S)-3-allyl-3-hydroxymethyl oxindole to (3S)-1′-benzyl-5-(iodomethyl)-4,5-dihydro-2H-spiro[furan-3,3′-indolin]-2′-one. The optically active 3-substituted-3-hydroxymethyl oxindoles and spiro-oxindoles are among the key synthons in the synthesis of potentially biologically active molecules.
- Kumar, Naveen,Kumar, Akshay,Sahoo, Subash Chandra,Chimni, Swapandeep Singh
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supporting information
p. 1377 - 1394
(2020/11/23)
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- Acylation of oxindoles using methyl/phenyl estersviathe mixed Claisen condensation - an access to 3-alkylideneoxindoles
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Predominantly, aggressive acid chlorides and stoichiometric coupling reagents are employed in the acylating process for synthesizing carbonyl tethered heterocycles. Herein, we report simple acyl sources,viz. methyl and phenyl esters, which acylate oxindolesviathe mixed Claisen condensation. This straightforward protocol is mediated by LiHMDS and KOtBu and successfully applied to a wide range of substrates. It is a noteworthy transformation that skips the stepwise generation of enolates and acylation, and the reaction is performed at a moderate temperature with no side reactions. This protocol produces the first examples ofortho-substituents in an aryl ring flanked with electron-donating and electron-withdrawing substrates. Interestingly, robust organometallic ferrocenyl methyl ester cleaved under these conditions with ease. Furthermore, biologically important Tenidap's analog was synthesized by this protocol.
- Gandhi, Thirumanavelan,Nagaraja, C. M.,Panyam, Pradeep Kumar Reddy,Rajeshwaran, Purushothaman,Sreedharan, Ramdas,Yadav, Saurabh
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supporting information
p. 3843 - 3847
(2020/06/03)
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- Annulation reaction of cyclic pyridinium ylides with: In situ generated azoalkenes for the construction of spirocyclic skeletons
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Two new types of cyclic pyridinium ylides were designed and further used in reactions with azoalkenes to access structurally diverse spirocyclic compounds. A range of spiropyrazoline oxindoles could be smoothly obtained in up to 99% yield via a [4 + 1] annulation process with oxindole 3-pyridinium ylides as C1 synthons. Similarly, a series of spiropyrazoline indanones could be prepared with indanone 2-pyridinium ylides as C1 synthons. This work represents the first example of cyclic pyridinium ylides as C1 synthons for the efficient construction of spirocyclic compounds.
- Quan, Bao-Xue,Yuan, Wei-Cheng,Zhang, Ming-Liang,Zhang, Xiao-Mei,Zhao, Jian-Qiang,Zhou, Ming-Qiang,Zhuo, Jun-Rui
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supporting information
p. 1886 - 1891
(2020/03/23)
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- Design, synthesis, and biological evaluation of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide conjugates as potent carbonic anhydrase I, II, IX, and XIII inhibitors
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A series of 1,2,3-triazole-linked triazino[5,6-b]indole-benzene sulfonamide hybrids (6a– 6o) was synthesized and evaluated for carbonic anhydrase (CA, EC 4.2.1.1) inhibitory activity against the human (h) isoforms hCA I, II, XIII (cytosolic isoforms), and hCA IX (transmembrane tumor-associated isoform). The results revealed that the compounds 6a–6o exhibited Ki values in the low to medium nanomolar range against hCA II and hCA IX (Kis ranging from 7.7 nM to 41.3 nM) and higher Ki values against hCA I and hCA XIII. Compound 6i showed potent inhibition of hCA II (Ki = 7.7nM), being more effective compared to the standard inhibitor acetazolamide (AAZ) (Ki = 12.1 nM). Compounds 6b and 6d showed moderate activity against hCA XIII (Ki= 69.8 and 65.8 nM). Hence, compound 6i could be consider as potential lead candidate for the design of potent and selective hCA II inhibitors.
- Angeli, Andrea,Arifuddin, Mohammed,Biswas, Rashmita,Chinchilli, Krishna Kartheek,Korra, Laxman Naik,Supuran, Claudiu T.,Thacker, Pavitra S.
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- Chiral naphthyl-C2-indole as scaffold for phosphine organocatalysis: Application in asymmetric formal [4 + 2] cycloaddition reactions
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The applications of a newly designed chiral naphthyl-C2-indole bifunctional phosphine organocatalyst in stereoselective formal [4 + 2] cycloaddition reactions were reported. The chiral naphthyl-C2-indole skeleton was introduced to bifunctional phosphine o
- He, Tingting,Peng, Lei,Li, Shan,Hu, Fangli,Xie, Chuandong,Huang, Shengli,Jia, Shiqi,Qin, Wenling,Yan, Hailong
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supporting information
p. 6966 - 6971
(2020/09/15)
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- Palladium-Catalyzed Cascade Hydrosilylation and Amino-Methylation of Isatin Derivatives
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We demonstrate that using palladium acetate as a catalyst for reduction of DMF and isatin derivatives by hydrosilanes, a cascade hydrosilylation and amino-methylation reaction can be realized. With DMF as a reactant and a solvent, the in-situ generated siloxymethylamine intermediate, an adduct of DMF and hydrosilanes, smoothly participates in the successive stages, providing a serials of Si, N-functionalized indolin-2-ones in moderate to good yields. This strategy exhibits high chemoselectivity toward carbonyl moieties reduction among the substrates. (Figure presented.).
- Liu, Yue,Xia, Yun-Tao,Cui, Su-Hang,Ji, Yi-Gang,Wu, Lei
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supporting information
p. 2632 - 2636
(2020/06/02)
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- Synthesis and selective inhibitory effects of some 2-oxindole benzenesulfonamide conjugates on human carbonic anhydrase isoforms CA I, CA II, CA IX and CAXII
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Three series of 2-oxindole benzenesulfonamide conjugates with different linkers were prepared by the condensation reaction of isatin derivatives 1a-e with different benzenesulfonamides. They were screened for their ability to inhibit human (h) carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX and hCA XII. Many compounds revealed promising activity and selectivity toward CAI, CAII and CAIX compared to acetazolamide (AAZ) especially compounds 2b (KI = 97.6, 8.0 nM against hCA I, hCA II, respectively) and 3a (KI = 90.2, 6.5 and 21.4 nM against hCA I, hCA II and hCA IX, respectively) relative to AAZ (KI = 250, 12 and 25 nM). Additionally, compound 4a revealed the highest activity against hCA II and hCA IX with KI of 3.0 and 13.9 nM, respectively. Docking of 2b, 3a and 4a into the active site of CA I, II, IX and XII revealed binding mode comparable to AAZ confirming the inhibition results.
- George, Riham F.,Said, Mona F.,Bua, Silvia,Supuran, Claudiu T.
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- NHC-Catalyzed Aldol-Like Reactions of Allenoates with Isatins: Regiospecific Syntheses of γ-Functionalized Allenoates
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An N-heterocyclic carbene (NHC) catalyzed γ-specific aldol-like reaction between allenoates and isatins has been achieved under mild conditions, giving trisubstituted allene derivatives bearing isatin moiety in moderate to good yields with high diastereoselectivity and excellent atom efficiency. The DFT computations indicated that the formation of the γ-adduct was more energetically favorable than that of the α-adduct. The result reported herein opens a new route for NHC-promoted allenoate-involved reaction.
- Li, Sha,Tang, Ziwei,Wang, Yang,Wang, Dan,Wang, Zhanlin,Yu, Chenxia,Li, Tuanjie,Wei, Donghui,Yao, Changsheng
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supporting information
p. 1306 - 1310
(2019/02/26)
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- A C=O???Isothiouronium Interaction Dictates Enantiodiscrimination in Acylative Kinetic Resolutions of Tertiary Heterocyclic Alcohols
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A combination of experimental and computational studies have identified a C=O???isothiouronium interaction as key to efficient enantiodiscrimination in the kinetic resolution of tertiary heterocyclic alcohols bearing up to three potential recognition motifs at the stereogenic tertiary carbinol center. This discrimination was exploited in the isothiourea-catalyzed acylative kinetic resolution of tertiary heterocyclic alcohols (38 examples, s factors up to >200). The reaction proceeds at low catalyst loadings (generally 1 mol %) with either isobutyric or acetic anhydride as the acylating agent under mild conditions.
- Greenhalgh, Mark D.,Smith, Samuel M.,Walden, Daniel M.,Taylor, James E.,Brice, Zamira,Robinson, Emily R. T.,Fallan, Charlene,Cordes, David B.,Slawin, Alexandra M. Z.,Richardson, H. Camille,Grove, Markas A.,Cheong, Paul Ha-Yeon,Smith, Andrew D.
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supporting information
p. 3200 - 3206
(2018/02/22)
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- Concise approach to the syntheses of (±)-gliocladin C and related diketopiperazine alkaloids
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A unique approach to the diketopiperazine indole alkaloid (±)-gliocladin C was developed and applied to formal syntheses of the related alkaloids (±)-gliocladine C and (±)-T988C. The key features of the strategy include an unprecedented nucleophilic addition of a diketopiperazine to an isatin derivative followed by a Friedel-Crafts alkylation of the resultant tertiary alcohol with indole to establish the critical quaternary center. Subsequent reduction of the intermediate oxindole moiety and cyclization then delivered a pivotal hexahydropyrrolo[2,3-b]indole diketopiperazine intermediate that was readily converted into (±)-gliocladin C as well as racemic versions of key intermediates in the Overman syntheses of (+)-gliocladine C and (+)-T988C.
- Hodges, Timothy R.,Benjamin, Noah M.,Martin, Stephen F.
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p. 3329 - 3338
(2018/04/19)
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- Novel hydrazido benzenesulfonamides-isatin conjugates: Synthesis, carbonic anhydrase inhibitory activity and molecular modeling studies
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As a part of our ongoing efforts towards developing novel carbonic anhydrase inhibitors based on the isatin moiety, herein we report the synthesis and biological evaluation of novel sulfonamides (5a-h, 10a-g and 11a-c) incorporating substituted 2-indolinone moiety (as tail) linked to benzenesulfonamide (as zinc anchoring moiety) through a hydrazide linker. The synthesized sulfonamides were evaluated in vitro for their inhibitory activity against the following human (h) carbonic anhydrase (hCA, EC 4.2.1.1) isoforms, hCA I, II, IX and XII. All these isoforms were inhibited by the sulfonamides reported here in variable degrees. hCA I was inhibited with KIs in the range of 671.8: 3549.5 nM, hCA II in the range of 36.8: 892.4 nM; hCA IX in the range of 8.9: 264.5 nM, whereas hCA XII in the range of 9.0: 78.1 nM. In particular, compound 10b emerged as a single-digit nanomolar hCA IX and XII inhibitor (8.9 and 9.2 nM, respectively). Molecular docking studies carried out for compound 10b within the hCA II, IX and XII active sites allowed us to rationalize the obtained inhibition results.
- Abo-Ashour, Mahmoud F.,Eldehna, Wagdy M.,Nocentini, Alessio,Ibrahim, Hany S.,Bua, Silvia,Abou-Seri, Sahar M.,Supuran, Claudiu T.
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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 Spiro[oxindole-3,2′-pyrrolidine] Derivatives from Benzynes and Azomethine Ylides through 1,3-Dipolar Cycloaddition Reactions
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A novel synthetic strategy employing benzyne and azomethine ylides for the construction of spiro[oxindole-3,2′-pyrrolidine] derivatives has been achieved in good yields. The ketimines obtained from the condensation of isatins with CF3CH2NH2 react with benzyne in the presence of weak bases such as TBAF or TBAT. This mild practical 1,3-dipolar cycloaddition provides an efficient route to access biologically active compounds.
- Ryu, Heesun,Seo, Jeongseob,Ko, Haye Min
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p. 14102 - 14109
(2018/11/21)
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- Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates
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The previously unexplored Grignard addition to oxindoles provides a regiospecific approach to 2- and 2,3-disubstituted indole derivatives in high yields via a one-pot aromatization driven dehydration pathway. This method allows a convenient preparation of diallyl indoles that are used as ring-closing metathesis (RCM) precursors for the orthogonal synthesis of pyrido[1,2-a]indoles and carbazoles. The synthetic utility of this method is illustrated by the synthesis of a microtubulin inhibitor and naturally occurring carbazole alkaloids.
- Mandal, Tirtha,Chakraborti, Gargi,Karmakar, Shilpi,Dash, Jyotirmayee
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supporting information
p. 4759 - 4763
(2018/08/24)
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- Indium-mediated Palladium-catalyzed Allylic Alkylation of Isatins with Alkynes
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An unprecedented indium-mediated palladium-catalyzed allylic alkylation of isatins with alkynes is disclosed. This reaction provides a new, practical, and straightforward route to access 3-allyl-3-hydroxy-2-oxindoles in good yields with broad substrate scope and scalability, exhibiting high atom and step economy. A primary mechanistic study reveals that indium played two roles in the reaction, first as a reductant and second as a Lewis acid. Compared with previous methods, our strategy eliminated the steps for the separation and purification of the reaction intermediates, as well as pre-installing leaving groups to allylic substrates. Moreover, our reaction did not employ moisture-sensitive allylic metal species and stoichiometric oxidants. (Figure presented.).
- Wu, Zijun,Fang, Xinxin,Leng, Yuning,Yao, Hequan,Lin, Aijun
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supporting information
p. 1289 - 1295
(2018/02/21)
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- Organocatalytic Asymmetric Synthesis of Bridged Acetals with Spirooxindole Skeleton
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The first highly diastereo- and enantioselective synthesis of bridged O,O-acetals embedded with spirooxindoles has been developed. Dioxindoles and 2-hydroxy cinnamaldehydes were employed as the reaction partners in this method. The desired products were obtained via diaryl prolinol TBS ether catalyzed Michael reaction followed by acetal formation with TFA.
- Balha, Megha,Pan, Subhas Chandra
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p. 14703 - 14712
(2018/11/23)
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- Synthesis, molecular structure, quantum mechanical studies and urease inhibition assay of two new isatin derived sulfonylhydrazides
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Two new isatin derivatives (E)-N′-(1-allyl-2-oxoindolin-3-ylidene)-4-methylbenzenesulfono-hydrazide (5) and (E)-N′-(1-allyl-2-oxoindolin-3-ylidene)-4-chlorobenzenesulfono-hydrazide (6) were synthesized in good yields by adopting two component synthetic methodology. The structure elucidation was accomplished with the help of UV–vis., FT-IR and NMR (1H and 13C) spectroscopic techniques. Suitable crystals were grown by slow evaporation method and structures were confirmed unequivocally with the help of single crystal X-ray diffraction analysis. Both isatin derivatives 5 and 6 exist in triclinic crystal packing having space group P-1. Crystal structures of both compounds showed that the geometries are stabilized by several intermolecular hydrogen bonds. Quantum mechanical calculations performed at density functional theory (DFT) level confirmed the experimental spectroscopic (UV–vis., FT-IR and 1H NMR) as well as X-ray diffraction results. Kinetic stability, reactivity, electrophilicity and nucleophilic behavior of both the derivatives was elaborated using frontier molecular orbitals (FMOs) and molecular electrostatic potential (MEP) analyses. Enzyme inhibition potential of both compounds was tested in vitro against Bacillus pasteurii urease and both compounds retarded the enzymatic activity with IC50 values of 39.46 ± 0.12 μM and 148.35 ± 0.16 μM respectively.
- Arshad, Muhammad,Jadoon, Mehwish,Iqbal, Zafar,Fatima, Mehwish,Ali, Muhammad,Ayub, Khurshid,Qureshi, Ashfaq Mahmood,Ashraf, Muhammad,Arshad, Muhammad Nadeem,Asiri, Abdullah M.,Waseem, Amir,Mahmood, Tariq
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- Synthesis and bio-evaluation of quaternary centered 3-hydroxy-3-(trifluoromethyl)indolin-2-one derivatives for anticancer and antimicrobial activities
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Abstract: A series of C(3)-trifluoromethylated compounds derived from N-substituted isatins were synthesized. The biological activity of all 3-hydroxy-3-(trifluoromethyl)indolin-2-one derivatives have been evaluated for in vitro cytotoxic activity and antibacterial activity. The active compounds were screened against nuclear xenobiotic receptor CAR (PDB ID: 1XLS), PIM1 kinase (PDB ID: 2O65), and CDK2 kinase (PDB ID: 3QHR) by using in silico molecular docking studies to obtain lead molecules. In addition to its potential anticancer activity, 5-bromo-3-ethynyl-3-hydroxy-1-(prop-2-yn-1-yl)indolin-2-one also showed specific antibacterial activity against S. aureus. Graphical abstract: [Figure not available: see fulltext.]
- Bikshapathi, Raktani,Prathima, Parvathaneni Sai,Yashwanth,Pamanji,Jagadeeshkumar,Maheshwari,Rao, J. Venkateswara,Murty,Rao, V. Jayathirtha
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p. 757 - 764
(2017/03/17)
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- Addition of carbamoylsilane to isatins: Highly efficient synthesis of 3-hydroxy-3-aminocarbonyl-2-oxindoles derivatives
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The first addition reaction between isatins and carbamoysilane has been developed which provides 3-hydroxy-3-aminocarbonyl-2-oxindoles core structures with excellent yields. Moreover, the reaction could undergo a one-pot synthesis process to furnish 3-hydroxy-3-aminocarbonyl-2-oxindole with gram-scale.
- Liang, Jin-Yan,Wang, Hui,Yang, Yan-Li,Shen, Shou-Jie,Chen, Jian-Xin
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supporting information
p. 2636 - 2639
(2017/06/14)
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- Double Carbonylation Using Glyoxal (HCOCOH): A Practical Copper-Promoted Synthesis of Isatins from Primary and Secondary Anilines
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A novel double carbonylation process has been demonstrated with easily available HCOCOH (glyoxal) as the double carbonylation reagent. Simple CuCl2?2H2O (copper(II) chloride dihydrate) was used as the oxidant for this transformation. Under optimized reaction conditions, various primary and secondary anilines were double-carbonylated to afford their corresponding isatins (26 examples, up to 80% yields). (Figure presented.).
- Kuan, Suzie Hui Chin,Sun, Wei,Wang, Lu,Xia, Chungu,Tay, Meng Guan,Liu, Chao
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supporting information
p. 3484 - 3489
(2017/09/06)
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- Isatin N,N′-Cyclic Azomethine Imine 1,3-Dipole and Abnormal [3 + 2]-Cycloaddition with Maleimide in the Presence of 1,4-Diazabicyclo[2.2.2]octane
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A new isatin N,N′-cyclic azomethine imine synthon was devised, and an unexpected abnormal [3 + 2]-cycloaddition with maleimide catalyzed by 1,4-diazabicyclo[2.2.2]octane (DABCO) has been disclosed. A variety of tricyclic spiropyrrolidine oxindoles bearing a dinitrogen heterocycle and succinimide scaffold were obtained in excellent yields (up to 96%) and diastereoselectivities (up to 97:3) under mild conditions.
- Wang, Xiao,Yang, Peng,Zhang, Yong,Tang, Chao-Zhe,Tian, Fang,Peng, Lin,Wang, Li-Xin
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supporting information
p. 646 - 649
(2017/02/10)
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- Electrocatalytic C-H/N-H Coupling of 2′-Aminoacetophenones for the Synthesis of Isatins
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2′-Aminoacetophenones undergo a C(sp3)-H oxidation followed by intramolecular C-N bond formation by virtue of a simple electrochemical oxidation in the presence of n-Bu4NI, providing various isatins with moderate to good yields. The reaction intermediates were detected, and a radical-based pathway was proposed.
- Qian, Peng,Su, Ji-Hu,Wang, Yukang,Bi, Meixiang,Zha, Zhenggen,Wang, Zhiyong
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p. 6434 - 6440
(2017/06/23)
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- Tertiary Amine-Catalyzed Difluoromethylthiolation of Morita–Baylis–Hillman Carbonates of Isatins with Zard's Trifluoromethylthiolation Reagent
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In this paper, we report that a novel tertiary amine-catalyzed [3+2] annulation between Morita–Baylis–Hillman (MBH) carbonates derived from isatins with thiocarbonyl fluoride (F2C=S) in situ generated from Zard's reagent proceeds smoothly under mild conditions, affording difluoromethylthiolated spirocyclic oxindoles in good to excellent yields. Moreover, the asymmetric variant could be realized with a modified Cinchona alkaloid, giving the desired cyclic adducts in good to excellent yields with good enantioselectivities. (Figure presented.).
- Fan, Xing,Yang, Haibin,Shi, Min
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supporting information
p. 49 - 57
(2017/01/14)
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- Synthesis and evaluation of in?vivo antioxidant, in?vitro antibacterial, MRSA and antifungal activity of novel substituted isatin N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones
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Some new isatin N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazones 4a-t with different substituents at 1-, 5- and 7-positions of isatin ring have been synthesized by reaction of N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)thiosemicarbazide 2 with corresponding isatins 3a-t. Compounds 4a-t were evaluated in?vivo for antioxidant activity and in?vitro for anti-microorganism activities. The MIC values were found for Gram positive bacteria (MIC?=?1.56–6.25?μM), for Gram negative bacteria (MIC?=?12.5?μM), and for fungi Aspergillus niger (MIC?=?3.12–12.5?μM), Fusarium oxysporum (MIC?=?6.25–12.5?μM) and Saccharomyces cerevisiae (MIC?=?6.25–12.5?μM). Regarding the antioxidant activity, the SOD, GHS-Px and catalase activities of 4c-i and 4m-r were MIC?=?10.57–10.85, 0.27–0.93 and 345.45–399.75 unit/mg protein, respectively. Compounds 4e-h had MIC values of 0.78, 1.56, and 3.12?μM for three clinical MRSA isolates. Compound 4e showed the selective cytotoxic effects against some cancer (LU-1, HepG2, MCF7, P338, SW480, KB) cell lines and normal fibroblast cell line NIH/3T3.
- Thanh, Nguyen Dinh,Giang, Nguyen Thi Kim,Quyen, Tran Ha,Huong, Doan Thi,Toan, Vu Ngoc
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p. 532 - 543
(2016/08/12)
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- Autoxidation/Aldol Tandem Reaction of 2-Oxindoles with Ketones: A Green Approach for the Synthesis of 3-Hydroxy-2-Oxindoles
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In the presence of tetrabutylammonium fluoride and molecular sieves (MS) 4 ? in DMF, an efficient autoxidation reaction of 2-oxindoles with ketones under air at room temperature has been developed. This approach may provide a green, practical, and metal-free protocol for a wide range of biologically important 3-hydroxy-3-(2-oxo-alkyl)-2-oxindoles.
- Zhang, Qing-Bao,Jia, Wen-Liang,Ban, Yong-Liang,Zheng, Yong,Liu, Qiang,Wu, Li-Zhu
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supporting information
p. 2595 - 2598
(2016/02/27)
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- Substrates as Electron-Donor Precursors: Synthesis of Naphtho-Fused Oxindoles via Benzannulation of 2-Halobenzaldehydes and Indolin-2-ones
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An unusual benzannulation reaction has been realized by integrating intermolecular adol condensation with subsequent intramolercular base-promoted homolytic aromatic substitution. This novel cascade reaction provides a straightforward approach toward various naphtho-fused oxindoles from 2-halobenzaldehydes and indolin-2-ones in the presence of Cs2CO3 in DMSO. The enolates of indolin-2-ones as new and internal electron donors have been demonstrated to initiate intramolecular radical dehalogenative coupling.
- Jia, Feng-Cheng,Xu, Cheng,Zhou, Zhi-Wen,Cai, Qun,Wu, Yan-Dong,Wu, An-Xin
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supporting information
p. 5232 - 5235
(2016/11/02)
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- Squaramide-Catalyzed Enantioselective Cascade Approach to Bispirooxindoles with Multiple Stereocenters
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A bifunctional squaramide-catalyzed Michael/Michael cascade reaction for the construction of spirotetrahydrofuran bispirooxindoles was developed. The products were obtained in moderate to excellent yields with excellent diastereo- and enantioselectivities
- Zhao, Bo-Liang,Du, Da-Ming
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supporting information
p. 3992 - 3998
(2016/12/30)
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- Homocoupling of 3-Halooxindole via Visible-Light Photocatalysis: A Mild Access to 3,3′-Bioxindoles
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This paper introduces a simple way to the homocoupling of tertiary halides induced by photocatalysis. This method features mild reaction conditions, excellent functional group tolerance, high yields, low photocatalyst loading and successful application to the highly sterically hindered systems. On the basis of the reaction results, a novel stable-radical-induced homocoupling reaction mechanism has been proposed.
- Jia, Wen-Liang,He, Jian,Yang, Jia-Jing,Gao, Xue-Wang,Liu, Qiang,Wu, Li-Zhu
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p. 7172 - 7181
(2016/08/30)
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- A Palladium-Catalyzed Double Carbonylation Approach to Isatins from 2-Iodoanilines
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A high-yielding procedure for the synthesis of isatins has been developed. Sequential Pd-catalyzed double carbonylation of 2-iodoanilines with near stoichiometric amounts of CO followed by acid-promoted cyclization readily affords an array of isatins. The conversion of 2-iodoanilines to isatins in good to excellent yields was found to proceed with good functional group tolerance. This protocol proved adaptable to 13C-isotope labeling of isatins, which was extended to the synthesis of the 13C-isotope labeled antiviral drug metisazone and the experimental anti-schizophrenia drug ML137.
- Laursen, Simon R.,Jensen, Mikkel T.,Lindhardt, Anders T.,Jacobsen, Mikkel F.,Skrydstrup, Troels
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supporting information
p. 1881 - 1885
(2016/05/09)
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