1217-89-6Relevant articles and documents
Regio- and diastereoselective vinylogous Mannich addition of 3-alkenyl-2-oxindoles to α-fluoroalkyl aldimines
Liu, Yingle,Yang, Yi,Huang, Yangen,Xu, Xiu-Hua,Qing, Feng-Ling
, p. 67 - 72 (2015)
An efficient asymmetric vinylogous Mannich (AVM) addition reaction of 3-alkenyl-2-oxindoles to α-fluoroalkyl aldimines has been developed. This reaction provided various optical active α-alkylidene-δ-amino-δ-fluoroalkyl oxindoles in excellent yields, complete γ-site regioselectivity, and excellent diastereoselectivities.
Fluorous chiral bisoxazolines: Application in copper-catalyzed asymmetric α-hydrophosphonylation
Deng, Tao,Wang, Hongjun,Cai, Chun
, p. 5843 - 5846 (2014)
A copper-catalyzed asymmetric α-hydrophosphonylation of isatins with a novel fluorous bis(oxazoline) as a ligand is presented. The corresponding chiral α1-oxindole-α-hydroxyphosphonates were obtained in 30-91% yield with enantioselectivities up to 92%. The fluorous ligand can be easily recovered and reused at least 3 times without a significant loss in its activity. This journal is the Partner Organisations 2014.
Synthesis of Isatins through Direct Oxidation of Indoles with IBX-SO3K/NaI
Bredenkamp, Angla,Mohr, Fabian,Kirsch, Stefan F.
, p. 1937 - 1943 (2015)
The direct conversion of indoles into isatins is presented. The reagent mixture NaI/IBX-SO3K, containing a sulfonylated derivative of 2-iodoxybenzoic acid, was employed to trigger this oxidative process. Moreover, the synthetic route toward IBX-SO3K and the X-ray crystal structure of the title compound are described in great detail.
Water-Promoted Regiospecific Azidolysis and Copper-Catalyzed Azide-Alkyne Cycloaddition: One-Pot Synthesis of 3-Hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H-1,2,3-triazol-1-yl)methyl]indolin-2-ones
Kumar, Kapil,Konar, Debabrata,Goyal, Sandeep,Gangar, Mukesh,Chouhan, Mangilal,Rawal, Ravindra K.,Nair, Vipin A.
, p. 9757 - 9764 (2016)
An efficient, eco-friendly, base free, one-pot, sequential protocol was developed for epoxide azidolysis and copper-catalyzed azide-alkyne cycloaddition using water as the solvent for the synthesis of 3-hydroxy-1-alkyl-3-[(4-aryl/alkyl-1H-1,2,3-triazol-1-yl)methyl]indolin-2-ones. The optimized reaction conditions have been generalized in the case of aromatic as well as aliphatic alkyne partners to afford good yields and high regioselectivity.
Pushing the boundaries of vinylogous reactivity: Catalytic enantioselective Mukaiyama aldol reactions of highly unsaturated 2-silyloxyindoles
Curti, Claudio,Sartori, Andrea,Battistini, Lucia,Brindani, Nicoletta,Rassu, Gloria,Pelosi, Giorgio,Lodola, Alessio,Mor, Marco,Casiraghi, Giovanni,Zanardi, Franca
, p. 6433 - 6442 (2015)
The first example of catalytic, enantioselective hypervinylogous Mukaiyama aldol reaction (HVMAR) involving multiply unsaturated 2-silyloxyindoles is reported. The reaction utilizes a chiral Lewis base-catalyzed Lewis acid-mediated technology to deliver homoallylic 3-polyenylidene 2-oxindoles with extraordinary levels of regio-, enantio-, and geometrical selectivity. This work highlights a subtle yet decisive influence of the indole N-substituents on the propagation of the vinylogous reactivity space of the donor substrates up to ten bonds away from the origin of the vinylogy effect. Analysis of the 13C NMR chemical shifts of the C-ω remote site within homologous silyloxyindole donors enabled rationalization of the results and easy qualitative prediction of the HVMAR reactivity/inertia toward a given aldehyde acceptor.
Electrocatalytic C-H/N-H Coupling of 2′-Aminoacetophenones for the Synthesis of Isatins
Qian, Peng,Su, Ji-Hu,Wang, Yukang,Bi, Meixiang,Zha, Zhenggen,Wang, Zhiyong
, p. 6434 - 6440 (2017)
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.
The aggregation-induced emission enhancement properties of BF2 complex isatin-phenylhydrazone: Synthesis and fluorescence characteristics
Zheng, Jie,Huang, Fang,Li, Yujin,Xu, Tianwei,Xu, Hui,Jia, Jianhong,Ye, Qing,Gao, Jianrong
, p. 502 - 509 (2015)
Isatin-phenylhydrazone derivatives and their corresponding BF2 complexes were efficiently synthesised by a three-step reaction starting from isatin and phenylhydrazine hydrochloride. The fluorescence properties of the isatin-phenylhydrazone derivatives and derived BF2 complexes were investigated in different organic solvents, in the solid state and in mixed solvent solutions of THF and H2O. These fluorescent dyes exhibited low fluorescent intensity in solution but a high fluorescent intensity as aggregates and in their solid state due to the interesting aggregation-induced emission enhancement characteristics which were caused by the inhibition of intramolecular rotation in the single molecule state. Information supporting this inference was supported by single crystal X-ray analysis.
A Highly Stereoselective Chiral Auxiliary-assisted Reductive Cyclization to Furoindoline
Kumar, Kapil,More, Shital S.,Khatik, Gopal L.,Rawal, Ravindra K.,Nair, Vipin A.
, p. 2696 - 2702 (2017)
Highly stereoselective furoindoline derivatives were synthesized by exploring the imidazolidinone-based chiral auxiliary-mediated aldol adduct. The one-pot reductive cyclization was achieved through NiCl2.6H2O/NaBH4.
Enantio- And Diastereoselective Synthesis of Homoallylic α-Trifluoromethyl Amines by Catalytic Hydroalkylation of Dienes
Onyeagusi, Chibueze I.,Shao, Xinxin,Malcolmson, Steven J.
, p. 1681 - 1685 (2020)
We describe a strategy for the enantio- and diastereoselective synthesis of homoallylic α-trifluoromethyl amines by the catalytic hydroalkylation of terminal dienes. Trifluoromethyl-substituted isatin-derived azadienolate nucleophiles undergo γ-selective alkylation with a Pd-DTBM-SEGPHOS catalyst, which additionally promotes regioselective addition to the diene and delivers products in up to 86% yield, 10:1 dr, and 97.5:2.5 er.
Simple and efficient microwave assisted N-alkylation of isatin
Shmidt, Maria Sol,Reverdito, Ana Maria,Kremenchuzky, Lautaro,Perillo, Isabel Amalia,Blanco, Maria Mercedes
, p. 831 - 840 (2008)
We present herein the results of microwave promoted N-alkylations of isatin (1) with different alkyl, benzyl and functionalized alkyl halides. Reactions were carried out under different conditions, always employing methodologies compatible with MW assisted chemistry. Generation of isatin anion employing diverse bases and solvents or using the preformed isatin sodium salt was tested. The best results were achieved using K2CO3 or Cs 2CO3 and a few drops of N,N-dimethylformamide or N-methyl-2-pyrrolidinone. These reactions present noteworthy advantages over those carried out employing conventional heating.
An efficient synthesis of new spiro[indolo-3(1H),2′(3′H)-oxadiazolyl] and 1-(triazol-4-ylmethyl)isatin derivatives
Bouhfid, Rachid,Joly, Nicolas,Massoui, Mohamed,Cecchelli, Romeo,Lequart, Vincent,Martin, Patrick,Essassi, El Mokhtar
, p. 2949 - 2955 (2005)
The synthesis and the characterization of new isatin derivatives obtained by 1,3-dipolar cycloaddition reactions on allylisatin and propargylisatin are described. The products thus regiospecifically obtained in good yields bear oxadiazolyles or trizolyles
Iridium-Catalyzed Enantioselective and Diastereoselective Allylation of Dioxindoles: A One-Step Synthesis of 3-Allyl-3-hydroxyoxindoles
He, Rui,Wu, Shanchao,Tang, Haoming,Huo, Xiaohong,Sun, Zhenliang,Zhang, Wanbin
, p. 6183 - 6187 (2018)
An iridium-catalyzed asymmetric allylation of dioxindoles, 3-hydroxyoxindoles, regulated by prosthetic groups has been accomplished under mild conditions. The methodology is applicable to a diverse array of 3-hydroxyoxindole and cinnamyl acetate substrates. A range of 3-allyl-3-hydroxyoxindoles containing vicinal tetrasubstituted and trisubstituted stereocenters can be efficiently synthesized in one-step with excellent enantioselectivity (up to >99% enaniomeric excess (ee)) and good diastereoselectivity (up to 11:1 diastereomeric ratio (dr)).
Discovery and SAR of muscarinic receptor subtype 1 (M1) allosteric activators from a molecular libraries high throughput screen. Part 1: 2,5-Dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-ones as positive allosteric modulators
Han, Changho,Chatterjee, Arindam,Noetzel, Meredith J.,Panarese, Joseph D.,Smith, Emery,Chase, Peter,Hodder, Peter,Niswender, Colleen,Jeffrey Conn,Lindsley, Craig W.,Stauffer, Shaun R.
, p. 384 - 388 (2015)
Results from a 2012 high-throughput screen of the NIH Molecular Libraries Small Molecule Repository (MLSMR) against the human muscarinic receptor subtype 1 (M1) for positive allosteric modulators is reported. A content-rich screen utilizing an intracellular calcium mobilization triple-addition protocol allowed for assessment of all three modes of pharmacology at M1, including agonist, positive allosteric modulator, and antagonist activities in a single screening platform. We disclose a dibenzyl-2H-pyrazolo[4,3-c]quinolin-3(5H)-one hit (DBPQ, CID 915409) and examine N-benzyl pharmacophore/SAR relationships versus previously reported quinolin-3(5H)-ones and isatins, including ML137. SAR and consideration of recently reported crystal structures, homology modeling, and structure-function relationships using point mutations suggests a shared binding mode orientation at the putative common allosteric binding site directed by the pendant N-benzyl substructure.
Tumor-associated carbonic anhydrase isoform IX and XII inhibitory properties of certain isatin-bearing sulfonamides endowed with in vitro antitumor activity towards colon cancer
Eldehna, Wagdy M.,Nocentini, Alessio,Al-Rashood, Sara T.,Hassan, Ghada S.,Alkahtani, Hamad M.,Almehizia, Abdulrahman A.,Reda, Ahmed M.,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
, p. 425 - 432 (2018)
Three series of indolinone-based sulfonamides (3a–f, 6a–f and 9a–f) were in vitro evaluated as inhibitors of the tumor-associated carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA IX and XII, using a stopped-flow CO2 hydrase assay. All the investigated sulfonamides displayed single- or double-digit nanomolar inhibitory activities towards both hCA IX (KIs: 6.2–64.8 nM) and XII (KIs: 7.1–55.6 nM) isoforms. All sulfonamides (3a–f, 6a–f and 9a–f) were in vitro examined for their potential anticancer activity against colorectal cancer HCT-116 and breast cancer MCF-7 cell lines. Sulfonamide 9e was found to be the most potent counterpart against HCT-116 (IC50 = 3.67 ± 0.33 μM). Sulfonamide 9e displayed good selectivity profile for inhibition of the tumor-associated isoforms (CAs IX & XII) over the off-target cytosolic CAs I and II. 9e was screened for cell cycle disturbance and apoptosis induction in HCT-116 cells. It was found to persuade cell cycle arrest at G2-M stage as well as alter the Sub-G1 phase. Also, 9e induced the intrinsic apoptotic mitochondrial pathway in HCT-116 cells via down-regulation of the anti-apoptotic protein Bcl-2 level with concurrent boosting the pro-apoptotic Bax, caspase-9, caspase-3, cytochrome C and p53 levels.
Novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino) benzenesulfonamides: Synthesis, carbonic anhydrase inhibitory activity, anticancer activity and molecular modelling studies
Eldehna, Wagdy M.,Abo-Ashour, Mahmoud F.,Nocentini, Alessio,Gratteri, Paola,Eissa, Ibrahim H.,Fares, Mohamed,Ismael, Omnia E.,Ghabbour, Hazem A.,Elaasser, Mahmoud M.,Abdel-Aziz, Hatem A.,Supuran, Claudiu T.
, p. 250 - 262 (2017)
Herein we report the synthesis of two series of novel 4/3-((4-oxo-5-(2-oxoindolin-3-ylidene)thiazolidin-2-ylidene)amino)benzenesulfonamides (4a-m and 7a-g). All the newly prepared sulfonamides were in vitro investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, II, IV and IX, using a stopped-flow CO2 hydrase assay. In particular, hCA isoforms II and IX (tumor-associated) were more susceptible to inhibition by the synthesized derivatives, with KIs in the range of 2.6–598.2 nM for hCA II, and of 16.1–321 nM for hCA IX. All compounds (4a-m and 7a-g) were evaluated for their anti-proliferative activity against breast cancer MCF-7 and colorectal cancer Caco-2 cell lines. Compound 4c was found to be the most potent derivative against MCF-7 (IC50 = 3.96 ± 0.21 μM), while 4j was the most active member against Caco-2 cells (IC50 = 5.87 ± 0.37 μM). Compound 4c induced the intrinsic apoptotic mitochondrial pathway in MCF-7 cells; evidenced by the enhanced expression of the pro-apoptotic protein Bax and the reduced expression of the anti-apoptotic protein Bcl-2, and the up-regulated active caspase-9 and caspase-3 levels.
A novel synthesis of spiro-2,5-dihydro-1,2-λ5- oxaphospholes using a three-component reaction
Esmaeili, Abbas Ali,Amini, Saeid,Bodaghi, Asghar
, p. 1452 - 1454 (2007)
The zwitterionic intermediate generated from dialkyl acetylenedicarboxylate and triphenylphosphine on reaction with N-substituted isatins leads to new highly functionalized spiro-2,5-dihydro-1,2-oxaphospholes. Georg Thieme Verlag Stuttgart.
Rhodium(I)-Catalyzed Intermolecular Hydroacylation of α-Keto Amides and Isatins with Non-Chelating Aldehydes
Kou, Kevin G. M.,Longobardi, Lauren E.,Dong, Vy M.
, p. 2233 - 2237 (2015)
The application of the bidentate, electron-rich bisphosphine ligand, 1,3-bis(dicyclohexyl)phosphine-propane (dcpp), in rhodium(I)-catalyzed intermolecular ketone hydroacylation is herein described. Isatins and α-keto amides are shown to undergo hydroacylation with a variety of non-chelating linear and branched aliphatic aldehydes. Also reported is the synthesis of new bidentate chiral phosphine ligands, and their application in hydroacylation is discussed.
Organocatalytic Asymmetric Synthesis of Cyclic Acetals with Spirooxindole Skeleton
Shikari, Amit,Mandal, Koushik,Chopra, Deepak,Pan, Subhas Chandra
supporting information, p. 58 - 63 (2021/11/09)
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.).
Applications of Ytterbium(II) Reagent as Grignard Reagent and Single-Electron Transfer Reagent in the Synthesis of 3-Substituted 2-Oxindoles
Wang, Pengkai,Cao, Xuyan,Zhang, Songlin
supporting information, p. 3836 - 3846 (2021/07/02)
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.
Novel quinolone-based potent and selective HDAC6 inhibitors: Synthesis, molecular modeling studies and biological investigation
Relitti, Nicola,Saraswati, A. Prasanth,Chemi, Giulia,Brindisi, Margherita,Brogi, Simone,Herp, Daniel,Schmidtkunz, Karin,Saccoccia, Fulvio,Ruberti, Giovina,Ulivieri, Cristina,Vanni, Francesca,Sarno, Federica,Altucci, Lucia,Lamponi, Stefania,Jung, Manfred,Gemma, Sandra,Butini, Stefania,Campiani, Giuseppe
, (2020/11/24)
In this work we describe the synthesis of potent and selective quinolone-based histone deacetylase 6 (HDAC6) inhibitors. The quinolone moiety has been exploited as an innovative bioactive cap-group for HDAC6 inhibition; its synthesis was achieved by applying a multicomponent reaction. The optimization of potency and selectivity of these products was performed by employing computational studies which led to the discovery of the diethylaminomethyl derivatives 7g and 7k as the most promising hit molecules. These compounds were investigated in cellular studies to evaluate their anticancer effect against colon (HCT-116) and histiocytic lymphoma (U9347) cancer cells, showing good to excellent potency, leading to tumor cell death by apoptosis induction. The small molecules 7a, 7g and 7k were able to strongly inhibit the cytoplasmic and slightly the nuclear HDAC enzymes, increasing the acetylation of tubulin and of the lysine 9 and 14 of histone 3, respectively. Compound 7g was also able to increase Hsp90 acetylation levels in HCT-116 cells, thus further supporting its HDAC6 inhibitory profile. Cytotoxicity and mutagenicity assays of these molecules showed a safe profile; moreover, the HPLC analysis of compound 7k revealed good solubility and stability profile.
