- New nitroindazolylacetonitriles: Efficient synthetic access: Via vicarious nucleophilic substitution and tautomeric switching mediated by anions
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New N-Alkyl-nitroindazolylacetonitriles were efficiently obtained via vicarious nucleophilic substitution of N-methyl-nitroindazoles with 4-chlorophenoxyacetonitrile. All compounds were fully characterized by NMR and mass spectroscopy techniques and the structures of some of them were additionally confirmed by X-ray diffraction analysis data. Tautomeric switching was observed in this series of nitroindazolylacetonitriles upon addition of basic anions followed by UV-Vis spectrophotometric and 1H-NMR titrations. The formation of tautomeric species induced by anionic species was endorsed by Density Functional Theory calculations.
- Eddahmi, Mohammed,Moura, Nuno M. M.,Bouissane, Latifa,Gamouh, Ahmed,Faustino, Maria A. F.,Cavaleiro, José A. S.,Paz, Filipe A. A.,Mendes, Ricardo F.,Lodeiro, Carlos,Santos, Sérgio M.,Neves, Maria G. P. M. S.,Rakib, El Mostapha
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p. 14355 - 14367
(2019/09/30)
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- Synthesis and biological evaluation of indazole-4,7-dione derivatives as novel BRD4 inhibitors
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Bromodomain-containing protein 4 (BRD4) is known to regulate the expression of c-Myc to control the proliferation of cancer cells. Therefore, development of small-molecule inhibitors targeting the bromodomain has been widely studied. However, some clinical trials on BRD4 inhibitors have shown its drawbacks such as toxicity including the loss of organ weight. Here, we report the development of the novel and promising scaffold, 1H-indazol-4,7-dione, as a bromodomain inhibitor and synthesized derivatives for the inhibition of binding of bromodomain to acetylated histone peptide. Through this effort, we obtained 6-chloro-5-((2,6-difluorophenyl)amino)-1H-indazole-4,7-dione (5i), which showed a highly potent activity with a half-maximal inhibitory concentration (IC50) of 60?nM. The in vivo xenograft assay confirmed that the 1H-indazol-4,7-dione compound reduced the tumor size significantly. These results show that the 1H-indazol-4,7-dione scaffold is highly potent against bromodomain.
- Yoo, Minjin,Yoo, Miyoun,Kim, Ji Eun,Lee, Heung Kyoung,Lee, Chong Ock,Park, Chi Hoon,Jung, Kwan-Young
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- N-indazole substituted thiourea derivatives and preparation method and application thereof
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The invention discloses N-indazole substituted thiourea derivatives and a preparation method and application thereof and belongs to the technical field of chemical medicine.The thiourea derivatives are a series of compounds simultaneously containing the 1H-indazole ring structure and the asymmetrical thiourea structure, and the compounds are not reported in the literature.The bioactivity test result analysis of the thiourea derivatives show that the compounds are good in antioxidant activity, the average scavenging rate is above 80%, the scavenging rate of the compound 12b, the compound 12c, and the compound 12d and the compound 12h is higher than 90%, the scavenging activity IC50 of the compound 12h on DPPH is 0.14mg/mL; part of the target compounds has certain inhibition activity on herpes viruses, vaccinia viruses, reoviruses, Coxsackie viruses, Feline coronary herpes viruses, HIV viruses and the like, and the compound 12c and the compound 12n are high in antivirus activity; the synthesized compounds hopefully have new bioactivity which is not expounded, and a certain material basis is provided for the development of new medicine.
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Paragraph 0074; 0075; 0076; 0086; 0087; 0088
(2016/10/09)
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- SUBSTITUTED AROMATIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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The invention relates to substituted aromatic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions (formula (I)).
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Page/Page column 124; 125
(2010/11/18)
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- Efficient synthesis of 7-substituted or 3,7-disubstituted 1H-indazoles
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This work reports on the synthesis of the novel indazole scaffolds 7-OTf-1H-indazole (trifluoromethanesulfonic acid 1H-indazol-7-yl ester), 7-iodo-1H-indazole and 3-bromo-7-iodo-1H-indazole. These new compounds are potent building blocks in divergent syntheses of indazoles via palladium cross-coupling reactions. Georg Thieme Verlag Stuttgart.
- Cottyn, Betty,Vichard, Dominique,Terrier, Fran?ois,Nioche, Pierre,Raman
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p. 1203 - 1206
(2008/01/08)
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- An efficient synthesis of 1-H indazoles
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The reaction of substituted salicyaldehydes with hydrazine hydrochloride under different conditions gave the corresponding 1-H indazoles. However, the reaction of benzaldehydes with hydrazine hydrate under the same conditions yielded only hydrazones.
- Lokhande,Raheem, Abdul,Sabale,Chabukswar,Jagdale
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p. 6890 - 6892
(2008/02/12)
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- A mild and selective method for the N-Boc deprotection by sodium carbonate
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A cleavage of N-tert-butyloxycarbonyl protection by Na2CO3 is reported. The N-free products are obtained in excellent yields. The compatibility of the method with the presence of acidic or basic groups is demonstrated. The reactions were performed on indole, azaindole, indazole, pyrazole, indolinone, quinolinone, and oxazolone.
- El Kazzouli, Sa?d,Koubachi, Jamal,Berteina-Raboin, Sabine,Mouaddib, Abderrahim,Guillaumet, Gérald
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p. 8575 - 8577
(2007/10/03)
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- Heterocyclic substituted 2-methyl-benzimidazole antiviral agents
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The present invention concerns antiviral compounds, their methods of preparation and their compositions, and use in the treatment of viral infections. More particularly, the invention provides heterocyclic substituted 2-methylbenzimidazole derivatives for the treatment of respiratory syncytial virus infection.
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- Radical scavenging by N-aminoazaaromatics
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N-Aminoazaaromatics were found to react with nitric oxide in the presence of oxygen to afford deaminated products in high yields. The reaction proceeded almost instantaneously in various solvents including water, and one to two equivalent of NO was consumed depending upon the amount of oxygen coexisted, and 1 equivalent of N2O was released in the reaction. In addition, N-aminoazoles were deaminated by potassium superoxide to give parent azoles in good yields. Two equivalents of superoxide was consumed, and about half equivalents of both nitrite and nitrate ion were released. The results demonstrated that N-aminoazoles have ability to protect the biological system against the oxidation promoted by radicals such as nitrogen oxides and superoxide. Copyright (C) 2000 Elsevier Science Ltd.
- Itoh, Takashi,Miyazaki, Michiko,Maeta, Hiromi,Matsuya, Yuji,Nagata, Kazuhiro,Ohsawa, Akio
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p. 1983 - 1989
(2007/10/03)
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- Research in 7-aminoindazole series: Synthesis of new halo-7H-4-methylpyrazolo[1,5,4-ef][1,5]benzodiazepin-6-ones and 5H-9-halo-6-methylpyrazolo[1,5,4-ef][1,5]benzodiazepin-4-ones
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A new class of 7-aminohaloindazoles has been synthesized. Reactivity of the amino groups of these bicyclic systems has been investigated. The halogenated pyrazolo-1,5-benzodiazepinones have been synthesized by the condensation of 7-aminoindazoles with ethyl acetoacetate.
- Rakib,Benchidmi,Essassi,El Bouadili,Ibn Mansour,Bellan,Lopez,Lamande
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p. 339 - 345
(2007/10/03)
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- COMPETITIVE PATHWAYS IN THE REACTION BETWEEN AROMATIC AZOSULFIDES AND ENOLATES IN DMSO
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The outcome of the reaction between azosulfides 1 and ketone enolates is influenced by the presence of suitable alkyl substituents on the aryl moiety of 1.The system can thus be conveniently exploited for the selective synthesis of different classes of derivatives of remarkable applicative interest, namely α-aryl ketones, α-arylhydrazono ketones, or indazoles.
- Dell'Erba, Carlo,Novi, Marino,Petrillo, Giovanni,Tavani, Cinzia
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p. 409 - 410
(2007/10/02)
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- Phase Transfer Catalyzed Synthesis of Indazoles from o-Alkylbenzenediazonium Tetrafluoroborates
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Reaction of o-methyl- and o-ethylbenzenediazonium tetrafluoroborates with two equivalents of potassium acetate and five mole percent of 18-crown-6 in ethanol-free chloroform produce indazoles in good to excellent yields.Indazoles bearing either electron-withdrawing or electron-donating substituents may be prepared.
- Bartsch, Richard A.,Yang, Il-Woo
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p. 1063 - 1064
(2007/10/02)
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