- Design, synthesis and bioevaluation of novel 6-substituted aminoindazole derivatives as anticancer agents
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In the present study, a series of 6-substituted aminoindazole derivatives were designed, synthesized, and evaluated for bio-activities. The compounds were initially designed as indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors based on the structural feature of five IDO1 inhibitors, which are currently on clinical trials, and the important anticancer activity of the indazole scaffold. One of them, compound N-(4-fluorobenzyl)-1,3-dimethyl-1H-indazol-6-amine (36), exhibited a potent anti-proliferative activity with an IC50 value of 0.4 ± 0.3 μM in human colorectal cancer cells (HCT116). This compound also remarkably suppressed the IDO1 protein expression. In the cell-cycle studies, the suppressive activity of compound 36 in HCT116 cells was related to the G2/M cell cycle arrest. Altogether, the current findings demonstrate that compound 36 would be promising for further development as a potential anticancer agent.
- Anh, Le Viet,Hai, Dinh Thi Thanh,Han, Byung Woo,Hien, Tran Thi Thu,Hoang, Ngo Xuan,Hoang, Van-Hai,Long, Nguyen Huu,Luu, Hung N.,Luu, Thi-Thu-Trang,Ngo, Son Tung,Ngo, Thien,Nguyen, Thanh Xuan,Nguyen, Yen Thi Kim,Tran, Phuong-Thao,Van Hieu, Duong
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p. 45199 - 45206
(2020/12/30)
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- 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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- One-pot synthesis of new 6-pyrrolyl-N-alkyl-indazoles from reductive coupling of N-alkyl-6-nitroindazoles and 2,5-hexadione
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One-pot synthesis of 6-pyrrolyl-N-alkyl-indazoles by the reductive coupling of N-alkyl-6-nitroindazoles and 2,5-hexadione was investigated in the presence of different reducing agents (SnCl2/AcOH and In/AcOH in THF). Indazoles 5a-h and 6a-h wer
- El Ghozlani, Mohamed,Chicha, Hakima,Abbassi, Najat,Chigr, Mohamed,El Ammari, Lahcen,Saadi, Mohamed,Spinelli, Domenico,Rakib, El Mostapha
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supporting information
p. 113 - 117
(2015/12/23)
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- HEPARAN SULFATE BIOSYNTHESIS INHIBITORS FOR THE TREATMENT OF DISEASES
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Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions in need of inhibition of heparan sulfate biosynthesis.
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Paragraph 000413
(2016/05/02)
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- Discovery and synthesis of N2,N4-substitued- cycloalkyl[d]pyrimidine-2,4-diamine analogs: The first examples of small-molecular FGFR-1 activator
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A series of novel, cycloalkyl-modified pazopanib analogs 2 and 3 were designed and synthesized. Their kinase modulatory effects on FGFR-1, VEGFR-2, PDGFR-β, and c-KIT were evaluated by the caliper mobility shift assay. Introduction of cycloalkyl into the pyrimidine linker of pazopanib almost abolished the four kinases inhibitory potency of compounds 2 and 3, but surprisingly, resulted in good activation effects on FGFR-1. Compounds 3d and 3g showed double-digit, nanomolar, selective activation effects on FGFR-1, and could be classified as first-generation small molecular activators of FGFR-1 kinase.
- Li, Bao-Li,Xiao, Fang,Lu, Wen-Chao,Sun, Yu-Yun,Zhu, Jin,Li, Jian
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p. 989 - 994
(2014/08/18)
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- THIENO[3,2-D]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY FOR PROTEIN KINASES
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Provided are a thieno[3,2-d]pyrimidine derivative of formula (I) or a pharmaceutically acceptable salt thereof having inhibitory activity for protein kinase, and a pharmaceutical composition comprising same for prevention and treatment of abnormal cell growth diseases.
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Paragraph 0608; 0609; 0610
(2015/01/06)
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- Synthesis and biological evaluation of novel pazopanib derivatives as antitumor agents
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A series of novel pazopanib derivatives, 7a-m, were designed and synthesized by modification of terminal benzene and indazole rings in pazopanib. The structures of all the synthesized compounds were confirmed by 1H NMR and MS. Their inhibitory
- Qi, Haofei,Chen, Ligong,Liu, Bingni,Wang, Xinran,Long, Li,Liu, Dengke
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supporting information
p. 1108 - 1110
(2014/03/21)
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- Regioselective methylation of indazoles using methyl 2,2,2- trichloromethylacetimidate
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An efficient and regio selective synthesis of substituted 2-methyl-2H-indazoles using a methyl 2,2,2-trichloroacetimidate is described.
- Baddam, Sudhakar Reddy,Uday Kumar,Panasa Reddy,Bandichhor, Rakeshwar
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supporting information
p. 1661 - 1663
(2013/03/29)
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- An expedient, regioselective synthesis of novel 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]- and -[4,5-g]indazoles and their anticancer potential
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Several novel 2-alkylamino- and 2-alkylthiothiazolo[5,4-e]- and -[4,5-g]indazoles and their 6-alkyl and 8-alkyl derivatives have been synthesised in high overall yields starting from 5-nitro and 6-nitroindazoles in a three-step route involving the regioselective cyclisation of thioureidoindazoles and indazolyl dithiocarbamates as the key steps. Some assorted thiazoloindazoles have been screened for anticancer properties, which demonstrated the anticancer potential of at least one product, justifying its further follow-up.
- Chakrabarty, Manas,Kundu, Taraknath,Arima, Shiho,Harigaya, Yoshihiro
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p. 6711 - 6723
(2008/12/20)
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- Reduction of nitroindazoles: Preparation of new amino and chloroamino derivatives
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The synthesis of chloroaminoindazoles by the reduction of the nitro group of indazoles using stannous chloride in alcoholic acid solution is reported. Using catalytic hydrogenation with palladium the expected reduction to amino-indazoles occur.{A figure is presented}. Indazole Nitro Reduction Chlorination Aminochloroindazole Heterocycle.
- Miloudi, Abdellah,El Abed, Douniazed,Boyer, Gerard,Galy, Jean-Pierre
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p. 2595 - 2605
(2008/02/04)
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- Efficient and regioselective synthesis of 2-alkyl-2H-indazoles
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An efficient and regioselective synthesis of 2-methyl-2H-indazoles and 2-ethyl-2H-indazoles using trimethyloxonium tetrafluoroborate or triethyloxonium hexafluorophosphate is reported.
- Cheung, Mui,Boloor, Amogh,Stafford, Jeffrey A.
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p. 4093 - 4095
(2007/10/03)
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- A synthesis of 9-methoxy-1-methyl-1H,6H-pyrazolo[4,3-c]carbazole
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The synthesis of 9-Methoxy-1-methyl-1H,6H-pyrazolo[4,3-c]carbazole is reported in four steps from 6-nitroindazole. Palladium acetate mediated cyclization gave only the 'bent' tetracyclic derivative.
- Morel, Sandrine,Boyer, Gerard,Coullet, Fabien,Galy, Jean-Pierre
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p. 2443 - 2447
(2007/10/03)
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- SYNTHESIS OF SUBSTITUTED PYRAZOLO- AND PYRAZOLOPHENOTHIAZINE DERIVATIVES
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The synthesis of new pyrazolo- and phenothiazines by the Bernthsen thionation of N-arylindazoles obtained using organometalic compounds is reported.
- Boyer, Gerard,Galy, Jean Pierre,Barbe, Jacques
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p. 487 - 496
(2007/10/02)
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- Synthesis of Pyrazoloacridin-9(10H)-ones
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Eight pyrazoloacridin-9(10H)-ones were prepared in a three step procedure from 5- and 6-nitroindazoles.Palladium catalysed hydrogenation of nitroindazoles afforded the corresponding 5- and 6-aminoindazoles.These, in turn, reacted with o-chlorobenzoic acid under the conditions of the Ullman reaction to give anthranilic acids.Cyclisation of these acids by means of sulfuric acid led to the title compounds.If phosphoryl chloride was used, instead of sulfuric acid, a 9-chloroacridine derivative was obtained.All the compounds were characterised by 1H NMR spectroscopy.
- Boyer, Gerard,Galy, Jean-Pierre,Faure, Robert,Elguero, Jose,Barbe, Jacques
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p. 2601 - 2615
(2007/10/02)
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- SYNTHESIS OF 5-HYDROXY-4-NITROSOBENZOTRIAZOLES AND 6-HYDROXY-7-NITROSO-INDAZOLES AND THEIR SPLITTING INTO β-TRIAZOLYL- AND β-PYRAZOLYLACRYLIC ACIDS
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5-Hydroxy-4-nitrosobenzotriazoles and 6-hydroxy-7-nitrosoindazoles were synthesized.By the action of benzenesulfonyl chloride in an alkaline medium, only 5-hydroxy-4-nitroso-2-phenyl-benzotriazole and 1-methyl-6-hydroxy-7-nitrosoindazole split into 5-carb
- Stankyavichyus, A. P.,Terent'ev, P. B.,Bolotin, V. A.,Lashin, V. V.,Rakhimi, I. M.
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p. 403 - 409
(2007/10/02)
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