- 3-Arylidene-N-hydroxyoxindoles: A New Class of Compounds Endowed with Antitumor Activity
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A series of compounds containing the N-hydroxyoxindole scaffold were synthesized and evaluated for antitumor activity. The compounds showed potent antiproliferative activity against the wild-type p53 IGROV-1 ovarian carcinoma cell line and considerably lower efficacy against the mutant IGROV-1/Pt1 subline that lacks p53 function. The differential response of ovarian carcinoma cells depending on p53 status was also reflected in the varied susceptibility to apoptosis of the treated cell lines. These results support a role for the p53 transcription factor as a determinant of cytotoxicity. The therapeutic potential of the most promising compound of the series was evaluated in the treatment of an IGROV-1 xenograft growing as ascitic tumor in mice. Using intraperitoneal administration, daily treatment with the compound for four weeks produced a significant delay in the onset of ascites.
- Musso, Loana,Cincinelli, Raffaella,Zuco, Valentina,De Cesare, Michelandrea,Zunino, Franco,Fallacara, Anna Lucia,Botta, Maurizio,Dallavalle, Sabrina
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Read Online
- Intermediate analogue inhibitors of mandelate racemase: N-Hydroxyformanilide and cupferron
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Mandelate racemase (MR) catalyzes the 1,1-proton transfer that interconverts the enantiomers of mandelate. The transition state/intermediate analogues N-hydroxyformanilide (Ki = 2.79 ± 0.19 μM) and cupferron (Ki = 2.67 ± 0.09 μM) are
- Bourque, Jennifer R.,Burley, Rodney K.M.,Bearne, Stephen L.
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Read Online
- Metal- and Oxidant-Free Modular Approach to Access N-Alkoxy Oxindoles via Aryne Annulation
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An unprecedented metal- and oxidant-free (intermolecular) approach to access N-alkoxy oxindoles via [3 + 2] cycloadition of in situ generated electrophilic species viz. aryne and (putative) aza-oxyallyl cation is reported. This approach is amenable to both C3-unsubstituted as well as C3-substituted oxindoles. A one-pot manipulation further makes this reaction highly practical. The versatility of this approach was demonstrated through valuable synthetic transformations.
- Singh, Ritesh,Nagesh, Kommu,Yugandhar, Doddapaneni,Prasanthi
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p. 4848 - 4853
(2018/08/24)
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- A safe and selective method for reduction of 2-nitrophenylacetic acid systems to N-aryl hydroxamic acids using continuous flow hydrogenation
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The cyclic hydroxamic acid functional group is critical to the biological activity of numerous natural products and drug candidates. Efficient, reliable, and green synthetic methods to produce cyclic hydroxamic acids are needed. Herein, flow hydrogenation has been explored as a novel approach toward achieving the selective partial reduction of 2-nitrophenylacetic acid to 1-hydroxyindolin-2-one. The bidentate ligand, 1,10-phenanthroline, has been identified as a unique inhibitor for modulating product selectivity in this Pt/C-catalyzed process. Under the newly optimized reaction conditions, the targeted hydroxamic acid is produced with high selectivity (49:1) over the lactam by-product. The scope of the reaction is demonstrated for a variety of 2-nitrophenylacetic acid derivatives.
- Ichire, Ogar,Jans, Petra,Parfenov, Galina,Dounay, Amy B.
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supporting information
p. 582 - 585
(2017/01/16)
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- Synthesis of o-Aminophenols via a Formal Insertion Reaction of Arynes into Hydroxyindolinones
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A novel approach toward the synthesis of sterically hindered o-aminophenols has been achieved by a formal aryne insertion into hydroxyindolinones. This transformation offers a rapid and efficient entry to diverse o-aminophenol scaffolds under mild transit
- Chen, Zhilong,Wang, Qiu
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supporting information
p. 6130 - 6133
(2016/01/09)
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- A nitrophenyl-based prodrug type for colorectal targeting of prednisolone, budesonide and celecoxib
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Celecoxib is a COX-2 inhibitor drug that can be used to reduce the risk of colorectal adenocarcinoma. Glucocorticoids are used in the treatment of inflammatory bowel disease. A limitation to the use of both drug types is that they undergo absorption from the intestinal tract with serious side effects. The prodrug systems introduced here involve forming a nitro-substituted acylsulfonamide group in the case of celecoxib and a nitro-substituted 21-ester for the glucocorticoids. Drug release is triggered by the nitro reductase action of the colonic microflora, liberating a cyclization competent species. The release of the active parent drugs was evaluated in vitro using Clostridium perfringens and epithelial transport through Caco-2 monolayer evaluation was carried out to estimate the absorption properties of the prodrugs compared to the parental drugs.
- Marquez Ruiz, Juan F.,Kedziora, Kinga,Pigott, Maria,Keogh, Brian,Windle, Henry,Gavin, Jason,Kelleher, Dermot P.,Gilmer, John F.
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p. 1693 - 1698
(2013/04/10)
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- Reductive cyclizations of nitroarenes to hydroxamic acids by visible light photoredox catalysis
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We have developed a photocatalytic reduction of nitroarenes as an efficient, chemoselective route to biologically important N-phenyl hydroxamic acid scaffolds. Optimal conditions call for 2.5 mol% of a ruthenium photocatalyst, visible light irradiation, and a dihydropyridine terminal reductant. Because of the mild nature of the visible light activation, functional groups that might be sensitive to other non-photochemical reduction methods are easily tolerated. Georg Thieme Verlag Stuttgart New York.
- Cismesia, Megan A.,Ischay, Michael A.,Yoon, Tehshik P.
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p. 2699 - 2705
(2013/10/21)
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- PROTON ACCEPTOR IMINIUM/CARBOCATION-TYPE COUPLING AGENTS
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Novel iminium-type coupling agents containing proton acceptors in their iminium moiety, which can be used beneficially as coupling agents in various chemical polypeptide and/or polynucleotide syntheses, and are particularly useful as yield enhancing and racemization suppressing coupling agents for use in peptide syntheses, are disclosed. Further disclosed are a process of preparing such iminium-type coupling agents and their use in the preparation of polypeptides and/or polynucleotides.
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- Synthesis and application of N-hydroxylamine derivatives as potential replacements for HOBt
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Several heterocycles containing N-hydroxylamine were prepared and tested as coupling additives to replace the use of N-hydroxybenzolriazole (HOBt.) derivatives. On the basis of our results on coupling yield and racemization-suppressing properties, we propose N-hydroxyindolin-2-one and 6- cfiloro-N-hydroxy-2-phenylbenzimidazole as suitable substitutes for HOBt. Wiley-VCH Verlag GmbH & Co. KGaA.
- El-Faham, Ayman,Albericio, Fernando
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supporting information; experimental part
p. 1499 - 1501
(2009/07/11)
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- Efficient approaches to S-alkyl-N-alkylisothioureas: Syntheses of histamine H3 antagonist clobenpropit and its analogues
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(Chemical Equation Presented) S-Alkyl-N-alkylisothioureas were efficiently synthesized via synthetic approach (A) using 3-phenylpro-pionyl isothiocyanate (PPI). The utility of the approach was proved by the syntheses of clobenpropit, a potent histamine H3 antagonist, and its analogues. Alternatively, clobenpropit could be prepared via intramolecular amide cleavage (B) with use of 2-nitrophenylacetyl isothiocyanate (NPAI).
- Yoneyama, Hiroki,Shimoda, Ayako,Araki, Lisa,Hatano, Kouta,Sakamoto, Yasuhiko,Kurihara, Takushi,Yamatodani, Atsushi,Harusawa, Shinya
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p. 2096 - 2104
(2008/09/19)
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- NOVEL THERAPEUTIC USE OF INDOLINONE DERIVATIVES
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Certain oxindole compounds have been found to be effective in experimentally induced autoimmune encephalitis and are therefore suggested for the preparation of a medicament for the prevention, treatment or amelioration of multiple sclerosis, or to delay the onset of or reduce the relapse rate in multiple sclerosis.
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Page/Page column 81
(2010/02/12)
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- The chemistry of indoles. CIII. Simple syntheses of serotonin, N-methylserotonin, bufotenine, 5-methoxy-N-methyltryptamine, bufobutanoic acid, N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine, and lespedamine based on 1-hydroxyindole chemistry
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Application of regioselective nucleophilic substitution reactions of 1-hydroxytryptamines to novel and simple syntheses of serotonin (1a), N-methylserotonin (1b), bufotenine (1c), 5-methoxy-N-methyltryptamine (2a), bufobutanoic acid (3a), N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine (4), and lespedamine (5) are described. Effective syntheses of 5-benzyloxytryptamine and 1-methoxy-2-oxindoles are also reported.
- Somei,Yamada,Kurauchi,Nagahama,Hasegawa,Yamada,Teranishi,Sato,Kaneko
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- IMIDAZOLE WITH ANGIOTENSIN II ANTAGONIST PROPERTIES
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This invention relates to novel substituted imidazole and triazole derivatives which antagonize the binding of angiotensin II to its receptors. The compounds are useful in the treatment of hypertension, heart failure, glaucoma, and hyperaldosteronism. Methods of making the compounds, novel intermediates useful in the preparation of the compounds, pharmaceutical compositions containing the compounds, and methods of using them are also covered.
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- CYCLIZATION WITH NITRENIUM IONS GENERATED FROM N-METHOXY- OR N-ALLYLOXY-N-CHLOROAMIDES WITH ANHYDROUS ZINC ACETATE. SYNTHESIS OF N-HYDROXY- AND N-METHOXYNITROGEN HETEROCYCLIC COMPOUNDS
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Electrophilic intramolecular aromatic substitution with an N-methoxy- or an N-allyloxyacylnitrenium ion, generated by treatment of an N-methoxy- or an N-allyloxy-N-chloroamide with anhydrous zinc acetate in nitromethane, leads to formation of a nitrogen h
- Kikugawa, Yasuo,Shimada, Masahiro,Matsumoto, Kazuhiro
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p. 293 - 302
(2007/10/02)
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- Preparation and study of chemical transformations of N-formyl-N-phenylhydroxylamines
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Nitrosobenzenes with CO2H 1b, CO2CH3 3b and CON(CH3)C6H5 4b ortho-substituents were obtained in a "redox" cell from the corresponding nitro compounds.In order to prepare the 3-oxo-1,2-dihydro-2,1-benzisoxazole-1-carbaldehyde from o-substituted N-formyl-N-phenylhydroxylamines, nitroso derivatives were formylated by glyoxylic acid.The N-formylbenzisoxazolone is unstable in the reaction medium and cannot be isolated.In addition to our study, we showed the unstability of N-formyl-N-phenylhydroxylamines and N-formylanilines in the presence of methanol without acetic acid; in an aqueous methanolic medium, formylation of nitrosoderivatives is equivalent to a reduction of the nitroso group.The mechanism was demonstrated by formylation of the nitrosobenzene and the electrogenerated 2-nitrosobenzene acetic acid 2b.Key Words: flow cell electrosynthesis / nitrosobenzenes / glyoxylic acid / formylation / N-formyl-N-phenylhydroxylamines / N-formylanilines / benzisoxazolones
- Guilbaud-Criqui, A.,Moinet, C.
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p. 164 - 172
(2007/10/02)
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- Synthesis of 1-Hydroxyoxindoles
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A convenient synthesis of various substituted 1-hydroxyoxindoles is described.
- Kende, Andrew S.,Thurston, Jeff
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p. 2133 - 2138
(2007/10/02)
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- A Novel Conversion of N-Aryl-N-methoxyamides into N-Arylhydroxamic Acids Using AlCl3/Thiol System
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Treatment of N-aryl-N-methoxyamides with AlCl3 in EtSH (or Me2S) generates the corresponding N-aryl-N-hydroxyamides in high yields.
- Kawase, Masami,Kitamura, Takahiro,Shimada, Masahiro,Kikugawa, Yasuo
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p. 887 - 892
(2007/10/02)
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- A SHORT STEP SYNTHESIS OF LESPEDAMINE
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A convenient synthetic method for 1-hydroxy-, 1-methoxy-, and 1-acetoxy-2-oxindole was disclosed starting from methyl 2-nitrophenylacetate.A five-step synthesis of lespedamine was achieved utilizing this method.
- Somei, Masanori,Sato, Haruhiko,Kaneko, Chikara
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p. 1797 - 1799
(2007/10/02)
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