Relevant bibliographies by topics / Oxindoles

Contents

  1. Journal articles
  2. Dissertations / Theses
  3. Books
  4. Book chapters
  5. Conference papers

Academic literature on the topic 'Oxindoles'

Author: Grafiati
Published: 4 June 2021
Last updated: 15 June 2025

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Journal articles on the topic "Oxindoles"

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Ziarani, Ghodsi Mohammadi, Fatemeh Javadi, and Fatemeh Mohajer. "The Molecular Diversity Scope of Oxindole Derivatives in Organic Synthesis." Current Organic Chemistry 25, no. 7 (2021): 779–818. http://dx.doi.org/10.2174/1385272825666210111112814.

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The role of oxindole derivatives is discussed as starting materials in diverse organic reactions, including two and more components, between the years 2014 until 2020. Oxindoles are famous because of their biological properties. For instance, chromanone-fused polycyclic pyrrolidinyl-dispirooxindoles, functionalized polycyclic spiro-fused carbocyclicoxindole, and 3,3-disubstituted oxindoles have anti-cancer, anti-tumor, and anti-microbial properties, respectively. Therefore, various methods for synthesizing the oxindole structures have received much attention in organic chemistry.
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Lingam, Kandapalam, Kodirajan Selvakumar, Periyasamy Amutha, and Paneerselvam Yuvaraj. "Controlled and Efficient Stereoselective Synthesis of Oxindole-Appended 1-Aza-1,3-butadiene Derivatives via a One-Pot Buchwald–Hartwig Amination/Elimination Strategy." Synthesis 50, no. 03 (2017): 599–606. http://dx.doi.org/10.1055/s-0036-1591493.

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The enamine-free, stereoselective synthesis of oxindole-appended­ 1-aza-1,3-butadienes with an electron-withdrawing-group at the 3-position has been achieved in good yields from (Z)-β-bromo-substituted Morita–Baylis–Hillman (MBH) adducts of oxindoles via a one-pot Buchwald–Hartwig amination/elimination strategy. The versatility of the (Z)-β-bromo MBH adducts of oxindoles was further demonstrated by the formation of π-conjugated oxindole derivatives in typical palladium­-catalysed coupling reactions.
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Chen, Bo, Jiaheng Lei, and Junling Zhao. "Michael Addition of Aryl Thiols to 3-(2,2,2-Trifluoroethylidene)Oxindoles under Catalyst-Free Conditions: The Rapid Synthesis of Sulfur-Containing Oxindole Derivatives." Journal of Chemical Research 42, no. 4 (2018): 210–14. http://dx.doi.org/10.3184/174751918x15240724383170.

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A mild and efficient catalyst-free method for the rapid synthesis at room temperature of 3-thiomethylated oxindole derivatives has been achieved via the Michael addition of aryl thiols to ring and 1-substituted 3-(2,2,2-trifluoroethylidene)oxindoles in dichloromethane. The method was applicable to a wide range of thiols and variously substituted 3-(2,2,2-trifluoroethylidene)oxindoles under mild conditions as demonstrated by the synthesis in high yields with good diastereoselectivities of 30 3-thiomethylated oxindoles bearing a trifluoromethyl group.
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Ortega-Martínez, Aitor, Cynthia Molina, Cristina Moreno-Cabrerizo, José Sansano, and Carmen Nájera. "Synthesis of 3,3-Disubstituted 2-Oxindoles by Deacylative Alkylation of 3-Acetyl-2-oxindoles." Synthesis 49, no. 23 (2017): 5203–10. http://dx.doi.org/10.1055/s-0036-1590880.

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An innovative and efficient monoalkylation and nonsymmetrical 3,3-dialkylation of oxindoles has been achieved. First, the monoalkylation of 3-acetyl-2-oxindoles can be performed in good yields under mild reaction conditions using alkyl halides and benzyltrimethylammonium hydroxide (Triton B) as base at room temperature. This methodology is applied to construct the synthetically challenging compound 1,3-dimethyl-2-oxindole. Subsequent deacylative alkylation (DaA) of the alkylated 3-acetyl-2-oxindoles with alkyl halides takes place efficiently using LiOEt or by conjugate addition with electron-deficient alkenes in the presence of Triton B at room temperature under argon, affording the corresponding unsymmetrically 3,3-disubstituted 2-oxindoles. This simple methodology has been applied to the synthesis of precursors of horsfiline, esermethole, physostigmine, and phenserine alkaloids.
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Jackson, Mark, Calvin Quince O'Broin, Helge Müller-Bunz та Patrick J. Guiry. "Enantioselective synthesis of sterically hindered α-allyl–α-aryl oxindoles via palladium-catalysed decarboxylative asymmetric allylic alkylation". Organic & Biomolecular Chemistry 15, № 38 (2017): 8166–78. http://dx.doi.org/10.1039/c7ob02161e.

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Jiang, Yan, Min-Yi Tian, Xiong-Li Liu та ін. "Highly Diastereo-, α-Regioselective Catalyst-Free Construction of Adjacent Dispirobisoxindoles with Three Contiguous Quaternary Carbon Centers". Synthesis 51, № 03 (2018): 683–92. http://dx.doi.org/10.1055/s-0037-1610290.

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A new methodology was developed for the highly diastereoselective construction of dispirobisoxindole scaffolds via a domino α-regioselective Michael/cyclization reaction sequence of 3-isothiocyanato oxindoles and isatylidene malononitriles under catalyst-free conditions. Complex polycyclic oxindoles featuring two side-by-side oxindole skeletons and three contiguous quaternary carbon centers were synthesized in up to 95% yield and >20:1 dr. This protocol could provide libraries of stereochemically rich small molecules that will help in the search for new bioactive molecules.
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Cong, Tiantian, Huamin Wang, Xiuzheng Li, Hai-Hong Wu, and Junliang Zhang. "Chiral bifunctional bisphosphine enabled enantioselective tandem Michael addition of tryptamine-derived oxindoles to ynones." Chemical Communications 55, no. 62 (2019): 9176–79. http://dx.doi.org/10.1039/c9cc04357h.

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A chiral phosphine-catalyzed tandem Michael addition of tryptamine-derived oxindoles to ynones was developed to synthesize spiro[pyrrolidine-3,3′-oxindole] in good yields, good to excellent enantio- and diastereoselectivities.
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Dalpozzo, Renato, and Raffaella Mancuso. "Enantioselective Vinylogous Reactions of 3-Alkylidene Oxindoles." Synthesis 50, no. 13 (2018): 2463–72. http://dx.doi.org/10.1055/s-0037-1609731.

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Oxindoles represent an important class of bioactive compounds and synthetic derivatives found in many natural products. Most of these compounds are chiral molecules and the challenge of their asymmetric synthesis has fascinated many research groups. In particular, the creation of chiral centers out of the oxindole ring by vinylogous addition to 3-alkylidene-substituted oxindoles (3-alkylidene-1,3-dihydro-2H-indol-2-ones) has emerged in recent years. This review aims to give an overview of this topic.1 Introduction2 Aldol and Mannich Reactions3 Addition to Unsaturated Carbonyl Compounds4 Addition to Nitroalkenes5 Miscellaneous6 Conclusion
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Tiwari, Keshri Nath, and Chandran R. "Krapcho Dealkoxycarbonylation Strategy of Ethyl Cyanoacetate for the Synthesis of 3-Hydroxy-3-cyanomethyl-2-oxindoles and 3,3′-Dicyanomethyl-2-oxindoles in a Reaction with Isatin." Synthesis 52, no. 15 (2020): 2233–40. http://dx.doi.org/10.1055/s-0040-1707816.

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A new strategy for the synthesis of 3-hydroxy-3-cyanomethyl-2-oxindoles and 3,3′-dicyanomethyl-2-oxindoles in a reaction of isatin with ethyl cyanoacetate by Krapcho dealkoxycarbonylation reaction in aqueous media is demonstrated. The reaction provides an easy access to synthetically and medicinally valuable oxindole alkylnitriles in good to very good yields. Wider substrate scope and operationally simple experimental procedures are highlighted features of the developed protocol. Based on control experiments, a plausible mechanism of reaction and synergistic effect of water is also rationalized.
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Cui, Hao, Ke Li, Yue Wang, et al. "Copper(i)/Ganphos catalysis: enantioselective synthesis of diverse spirooxindoles using iminoesters and alkyl substituted methyleneindolinones." Organic & Biomolecular Chemistry 18, no. 19 (2020): 3740–46. http://dx.doi.org/10.1039/d0ob00546k.

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A copper/Ganphos-catalyzed asymmetric 1,3-dipolar cycloaddition of glycine iminoesters with alkyl substituted 3-methylene-2-oxindoles is described, producing the spiro[pyrrolidin-3,3′-oxindole]s in good yields with high ee.
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Dissertations / Theses on the topic "Oxindoles"

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Edeson, Steven. "Synthesis and reactions of novel oxindoles." Thesis, University of Sheffield, 2015. http://etheses.whiterose.ac.uk/12114/.

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An important issue with the assignment of E/Z alkene geometry of 3-acylidene-oxindoles was addressed. A novel UV/Visible spectroscopic assay was developed in order to achieve this, taking advantage of contrasting electronic properties for different E/Z isomer sets. Moreover, a novel acylidene oxindole was prepared and used to provide further supporting evidence for this spectroscopic assay. Finally, the stability of related E/Z isomers was investigated, and indicated facile isomerisation to a thermodynamic minimum. A copper promoted cyclisation of o-nitrophenyl iodoacetylenes to 2-iodoisatogens was discovered. These compounds were applicable as precursors to novel isatins and consequently 3-acylidene oxindoles. The metal free aryl and alkyl cross coupling reactions of 2-iodoisatogens was developed, providing a divergent synthetic strategy to the medicinally relevant isatogen molecular group. Furthermore, an unprecedented isatogen mode of reactivity was discovered affording pseudoindoxyls, a privileged class of molecule. The mechanism for this transformation was proposed, based on control reactions and strong literature precedent.
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Richmond, Edward. "An asymmetric pericyclic cascade approach to oxindoles." Thesis, University of St Andrews, 2014. http://hdl.handle.net/10023/4459.

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The research in this thesis describes an asymmetric pericyclic cascade approach to the synthesis of a range of enantioenriched oxindoles using enantiopure oxazolidine derived nitrones and disubstituted ketenes. Chapter 1 aims to place this work in the context of the literature, describing other commonly employed or state-of-the-art asymmetric approaches to oxindoles and related compounds. Examples of where these approaches have been used successfully in the total synthesis of related indole alkaloids are also presented. The conception of this project within the group is also described alongside initial attempts to develop the first enantioselective variant of the same reaction using nitrone chiral auxiliaries. Chapter 2 details the optimisation of this asymmetric oxindole forming reaction by structural variation of the nitrone component, culminating in the preparation of an N-TIPBS nitrone based on an oxazolidine framework, which proved to be optimal for this process. Also detailed are attempts to gain insight towards the mechanism of this transformation and to understand the mode of chirality transfer. Chapter 3 details the use of the N-TIPBS nitrone scaffold as a transmitter of chiral information in the synthesis of 3-alkyl-3-aryloxindoles and spirocyclic oxindoles. Chapter 4 delineates the mechanism of this transformation as a pericyclic cascade process. The key stereo-determining features are discussed including the conformational preferences of such chiral oxazolidine derived nitrones and the influence of the N-protecting group on the stereochemical outcome. Synthetic endeavours to provide evidence as to the validity of this computational mechanistic rationale are also presented. Chapter 5 describes regioselectivity studies, and tolerance of both the racemic and asymmetric reactions to varying substitution on the nitrone N-aryl ring. Initial studies were undertaken using achiral nitrones before the interplay between regio- and stereoselectivity was explored, initially with enantiopure N-Boc Garner's aldehyde derived nitrones, and further with N-TIPBS nitrones. Chapter 6 initially describes attempts to transform this chiral auxiliary methodology into a catalytic asymmetric protocol, by investigating in situ ketene formation via various strategies including activation of carboxylic acids. Also described are investigations into related nitrone-ketenimine cycloadditions, and related [3+2] nitrone cycloadditions. Chapter 7 describes the application of this methodology toward the synthesis of compounds with biological relevance. The concise asymmetric synthesis of a Roche anti-cancer agent is outlined, as is the extension of this methodology to the synthesis of indole alkaloid-like species. Finally, the attempted application of this methodology toward the asymmetric synthesis of (+)-gliocladin C is outlined.
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Elderwish, Sabria. "Synthèse de spiro-oxindoles ligands des prohibitines." Thesis, Strasbourg, 2019. http://www.theses.fr/2019STRAF019.

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Les prohibitines-1 et 2 (PHB1 et PHB2) sont des protéines d’échafaudage qui coordonnent plusieurs voies de signalisation et qui représentent des cibles émergentes en cardiologie et en oncologie. L’étude du rôle des PHBs est gênée par la variété de leurs modifications post-traductionnelles et par la létalité consécutive à leur invalidation génétique. Dans ce travail de thèse, nous avons développé deux synthèses reproductibles d’un nouveau ligand de la PHB2, le 2'-phénylpyrrolidinyl-spirooxindole, et de ses analogues. Nous avons identifié des composés qui protègent les cardiomyocytes contre la toxicité de la doxorubicine, et établi les requis structuraux pour cette activité. Nous avons aussi synthétisé des outils qui ont permis de montrer qu’à la fois la PHB1 et la PHB2 se lient à ces spirooxindoles. Ces composés peuvent donc être utilisés comme sondes pharmacologiques pour étudier le rôle des PHBs et pourraient constituer une base pour le développement de nouvelles drogues pour traiter les affections cardiaques et les cancers
The scaffold proteins prohibitins-1 and 2 (PHB1/2) play many important roles in coordinating many cell signaling pathways and represent emerging targets in cardiology and oncology. The investigation of the diverse physiological roles of PHBs is hampered by the complexity of their various post-translational modifications and also by the lethality consecutive to their genetic inactivation.We report herein two convenient and robust syntheses of the new PHB ligand 2'-phenylpyrrolidinyl-spirooxindole and its analogs. We identified some analogs that protect cardiomyocytes against the toxicity induced by doxorubicin and identified the structural requirements for this activity. We also synthesized some tools that were used to find that both PHB1 and PHB2 are targeted by these spirooxindoles. Such compounds may be used as pharmacological probes to explore the role of PHBs and may provide the basis for the development of new drugs candidates to treat cardiac diseases or cancers
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Molina, Cynthia. "Síntesis de 2-oxindoles 3,3-disustituidos por alquilación desacilativa." Doctoral thesis, Universidad de Alicante, 2020. http://hdl.handle.net/10045/109416.

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Esta memoria consta de una introducción general y tres capítulos. En la introducción general, se muestra la importancia del anillo de oxindol, describiendo productos naturales o con actividad biológica que lo contienen en su estructura y comentando algunas de sus aplicaciones biológicas más relevantes. Además, se detallan diferentes técnicas para la síntesis de derivados de oxindol, destacando las metodologías que emplean la alquilación desacilativa. En el capítulo I se muestra una alquilación desacetilativa de derivados de 3-acetil-3-alquil-2-oxindoles con alquenos electrofílicos. En el capítulo II se describe la síntesis de derivados de 2-oxindoles 3,3-disustituidos a través de la alquilación desacetilativa usando haluros de alquilo y alquenos electrofílicos y mediante la alilación desacetilativa catalizada por paladio usando alcoholes alílicos. Finalmente, en el capítulo III, se estudia la reacción aldólica desacetilativa entre 3-fluorooxindoles y aldehídos.
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Repasky, Paul J. "Novel Trisubstituted Arylidene Oxindoles with Potent Anti-Apoptotic Properties." Wright State University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=wright1310326721.

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Tercel, Moana. "New routes to spiro-oxindoles for the synthesis of gelsemine." Thesis, University of Cambridge, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317870.

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Knisley, Kyle James. "Libraries from Libraries Approach to the Synthesis of Arylidene Oxindoles." Wright State University / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=wright1388766101.

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Belletti, Giada. "Organocatalytic Enantioselective Vinylogous Aldol-Lactonization Cascade Reaction of 3-Alkylidene Oxindoles to Trifluoromethyl Ketones." Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amslaurea.unibo.it/14463/.

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In this work, an highly enantioselective vinylogous aldol-lactonization cascade reaction of 3-alkylidene oxindole to α,β-unsaturated trifluoromethyl ketone, promoted by bifunctional organocatalysts, is presented. The reaction proceed through 1,2-addition followed by cascade lactonization to afford an unsaturated lactone bearing a chiral trifluoromethylated tetrasubstituted carbon stereocenter with high enantioselectivity and moderate yield. Nevertheless, also the two E/Z isomers of the correspondent 1,2-addition product are obtained.
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Toyoshima, Takeharu. "Synthesis of Oxindoles by Palladium Catalyzed Cyclization Reactions of 2-(Alkynyl)aryl Isocyanates with Nucleophiles." 京都大学 (Kyoto University), 2011. http://hdl.handle.net/2433/142568.

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Rousseau, Géraldine. "Synthèse et désymétrisation d'arylcyclohexa-2,5-diènes : application à la synthèse totale de l'épi-Elwesine." Thesis, Bordeaux 1, 2008. http://www.theses.fr/2008BOR13654/document.

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La désymétrisation d’arylcyclohexa-2,5-diènes est une méthode très efficace pour obtenir en une seule étape des squelettes complexes à partir de synthons simples. Lors de cette thèse, une nouvelle approche à la synthèse d’arylcyclohexadiènes porteur d’un centre quaternaire a été développée. L’une des structures synthétisées par cette voie a ensuite été désymétrisée par une réaction d’hydroamination diastéréosélective, nous permettant de réaliser la première synthèse énantiosélective de l’épi-Elwesine. Notre démarche s’est ensuite orientée vers la synthèse et la désymétrisation de nouveaux types de diènes spirocycliques de type oxindoles. La présence dans ces diènes de deux faces très différenciées nous a permis de réaliser des processus complètement diastéréosélectifs. De plus une nouvelle séquence réarrangement-alkylation a été mise au point, nous permettant d’accéder efficacement à des squelettes de type phénanthridinones de façon régio- et diastéréosélective
The desymmetrization of arylcyclohexa-2,5-dienes is a powerful method to synthesize complex structures from simple synthons in a single step. We first developed a new protocol to obtain arylcyclohexa-2,5-dienes bearing a quaternary center. One of these structures was desymmetrized via a diastereoselective hydroamination and further elaborated into epi-Elwesine, an Amaryllidaceae alkaloid. We next turned our attention towards the synthesis and desymmetrization of spirocyclic cyclohexadienes. Diastereoselective processes were carried out due to the presence of two well- differentiated faces. A new rearrangement-alkylation process was developed and provides efficient access to phenanthridinones regio- and diastereoselectively
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Books on the topic "Oxindoles"

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Rafipoor, Fereshteh. Synthesis of oxindole quionones and carboline quinones. Brunel University, 1991.

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Book chapters on the topic "Oxindoles"

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Russel, Jonathon S. "Oxindoles and Spirocyclic Variations: Strategies for C3 Functionalization." In Topics in Heterocyclic Chemistry. Springer Berlin Heidelberg, 2010. http://dx.doi.org/10.1007/7081_2010_50.

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Di Iorio, Nicola. "The Vinylogous Reactivity of Oxindoles Bearing Non-symmetric 3-Alkylidene Groups." In Springer Theses. Springer International Publishing, 2018. http://dx.doi.org/10.1007/978-3-319-74914-3_2.

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Reinecke, D. "The Oxindole-3-Acetic Acid Pathway in Zea mays." In Plant Growth Substances 1988. Springer Berlin Heidelberg, 1990. http://dx.doi.org/10.1007/978-3-642-74545-4_43.

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Moroni, Flavio, Raffaella Carpenedo, Guido Mannaioni, et al. "Studies on the Pharmacological Properties of Oxindole (2-Hydroxyindole) and 5-Hydroxyindole: Are They Involved in Hepatic Encephalopathy?" In Advances in Experimental Medicine and Biology. Springer US, 1997. http://dx.doi.org/10.1007/978-1-4615-5945-0_4.

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"Oxindoles." In Encyclopedia of Genetics, Genomics, Proteomics and Informatics. Springer Netherlands, 2008. http://dx.doi.org/10.1007/978-1-4020-6754-9_12071.

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Bergman, Jan. "Oxindoles." In Advances in Heterocyclic Chemistry. Elsevier, 2015. http://dx.doi.org/10.1016/bs.aihch.2015.08.001.

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DeRosa, Thomas F. "Aza-Oxindoles." In Advances in Synthetic Organic Chemistry and Methods Reported in US Patents. Elsevier, 2006. http://dx.doi.org/10.1016/b978-008044474-1/50015-3.

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"3-Hetero-3-Substituted Oxindoles." In Asymmetric Synthesis of 3,3-Disubstituted Oxindoles. WORLD SCIENTIFIC (EUROPE), 2019. http://dx.doi.org/10.1142/9781786347305_0006.

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Hof, K., K. M. Lippert, and P. R. Schreiner. "Michael Addition of Oxindoles to Maleimides." In Brønsted Base and Acid Catalysts, and Additional Topics. Georg Thieme Verlag KG, 2012. http://dx.doi.org/10.1055/sos-sd-205-00219.

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Hof, K., K. M. Lippert, and P. R. Schreiner. "Mannich Reaction of Oxindoles with Imines." In Brønsted Base and Acid Catalysts, and Additional Topics. Georg Thieme Verlag KG, 2012. http://dx.doi.org/10.1055/sos-sd-205-00234.

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Conference papers on the topic "Oxindoles"

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Santos, Maria, Elizabeth Lopes, Margarida Espadinha, Mattia Mori, and Maurizio Botta. "Enhancing anticancer activity of spiropyrazoline oxindoles by disrupting p53-MDMs PPIs." In 5th International Electronic Conference on Medicinal Chemistry. MDPI, 2019. http://dx.doi.org/10.3390/ecmc2019-06352.

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Macaev, Fliur. "Molecular architecture of chiral oxindoles as a facile platform to new drug candidates." In New frontiers in natural product chemistry, scientific seminar with international participation. Institute of Chemistry, 2021. http://dx.doi.org/10.19261/nfnpc.2021.ab09.

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Marini, Francesca, Luca Rossi, Luca Sancineto, Luana Bagnoli, and Claudio Santi. "Michael Initiated Ring Closure Reactions in Aqueous Medium for the Synthesis of Spiro Cyclopropyl Oxindoles." In The 18th International Electronic Conference on Synthetic Organic Chemistry. MDPI, 2014. http://dx.doi.org/10.3390/ecsoc-18-a020.

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Matheson, Christopher J., Kimberly A. Casalvieri, Donald S. Backos, Craig T. Jordan, and Philip Reigan. "Abstract C078: Substituted oxindoles as AMP-activated protein kinase (AMPK) inhibitors and their evaluation in models of leukemia." In Abstracts: AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; October 26-30, 2019; Boston, MA. American Association for Cancer Research, 2019. http://dx.doi.org/10.1158/1535-7163.targ-19-c078.

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Maldonado Rivera, José Luis, E. Pérez-Gutiérrez, M. Rodríguez, et al. "OLEDs fabricated by solution process based on a novel linear poly(arylene oxindole)." In Organic Light Emitting Materials and Devices XXII, edited by Franky So, Chihaya Adachi, and Jang-Joo Kim. SPIE, 2018. http://dx.doi.org/10.1117/12.2322752.

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Pireddu, Roberta, Harshani R. Lawrence, Mathew P. Martin, et al. "Abstract 3253: Novel oxindole inhibitors of Aurora A kinase: Structure based hit-to-lead approach." In Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL. American Association for Cancer Research, 2011. http://dx.doi.org/10.1158/1538-7445.am2011-3253.

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Delaisi, Christine, Isabelle Meaux, Odette Dos-Santos, et al. "Abstract 4648: In vitro characterization of spiro-oxindole-based modulators of the MDM2-p53 interaction and their interspecies selectivity." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-4648.

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Meaux, Isabelle, Cédric Barrière, Donna McEachern, et al. "Abstract 4731: Cytotoxic versus cytostatic effects in tumor models by spiro-oxindole-based modulators of the MDM2-p53 interaction." In Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL. American Association for Cancer Research, 2012. http://dx.doi.org/10.1158/1538-7445.am2012-4731.

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