- 2-oxadiazole-3-aminothiophene thieno-[2,3-b] pyridine derivative and preparing method and application thereof
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The invention belongs to the field of chemical pharmaceuticals, and particularly relates to a 2-oxadiazole-3-aminothiophene thieno-[2,3-b] pyridine derivative and a preparing method and application thereof. The structure of the 2-oxadiazole-3-aminothiophene thieno-[2,3-b] pyridine derivative is shown in the formula I. A compound of the 2-oxadiazole-3-aminothiophene thieno-[2,3-b] pyridine derivative has the good HCV inhibitory effect, and meanwhile shows the low cytotoxicity, and a new method is provided for development of an anti-HCV inhibitor. The general formula is defined in the description.
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Paragraph 0069-0071; 0084-0086
(2017/09/01)
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- A new series of HCV inhibitors based on a 2-(thieno[2,3B]pyridin-2-yl)-1,3,4-oxadiazole scaffold
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A new series of HCV inhibitors based on a 2-(thieno[2,3-b]pyridin-2-yl)-1,3,4-oxadiazole scaffold was developed. Detailed SAR investigations revealed the HCV inhibitory activity was sensitive to the size of C5, the C6-fused ring, and the size and flexibility of C5′ cycloalkane, which led to the identification of several compounds with potent inhibitory activity against HCV genotype 1b replicon. The most potent compound 10d showed ~100-fold improvement in potency compared with compound 1, with an EC50 of 0.039 μM, but without obvious cytotoxicity in vitro.
- Zuo, Wei-Qiong,Wang, Ning-Yu,Zhu, Yong-Xia,Liu, Li,Xiao, Kun-Jie,Zhang, Li-Dan,Gao, Chao,Liu, Zhi-Hao,You, Xin-Yu,Shi, Yao-Jie,Peng, Cui-Ting,Ran, Kai,Tang, Hong,Yu, Luo-Ting
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p. 40277 - 40286
(2016/05/24)
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- Highly selective trifluoroacetic ester/ketone metathesis: An efficient approach to trifluoromethyl ketones and esters
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A highly selective and atom efficient 'trifluoroacetic ester/ketone metathesis' has been sincerely witnessed. Enolizable alkyl (at least two non-hydrogen atoms) aryl ketones were found to react readily with ethyl trifluoroacetate under the promotion of NaH to afford trifluoroacetic ester/ketone exchange products, trifluoromethyl ketones (TFMKs), and aromatic acid esters, which were quite different from the general Claisen condensation products, 1,3-diketones. The outcome of the reaction between ketone and ethyl trifluoroacetate is strongly related to the structures of substrates, the steric congestion caused by alkyl group is in favor of the C-C bond cleavage. DFT investigation further disclosed that the metathesis reaction was a kinetically favored pathway. Using only a slight excess of cheap trifluoromethylation reagent, simple operation and mild conditions make it a practical method for preparation of TFMKs on large scale, as well as a new choice of converting aryl alkyl ketones to aromatic acid esters.
- Zhou, Yuhan,Yang, Dongmei,Luo, Gen,Zhao, Yilong,Luo, Yi,Xue, Na,Qu, Jingping
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p. 4668 - 4674
(2014/06/23)
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- Fused 3-hydroxy-3-trifluoromethylpyrazoles inhibit mutant huntingtin toxicity
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Here, we describe the selection and optimization of a chemical series active in both a full-length and a fragment-based Huntington's disease (HD) assay. Twenty-four thousand small molecules were screened in a phenotypic HD assay, identifying a series of compounds bearing a 3-hydroxy-3- trifluoromethylpyrazole moiety as able to revert the toxicity induced by full-length mutant Htt by up to 50%. A chemical exploration around the series led to the identification of compound 4f, which demonstrated to be active in a Htt171-82Q rat primary striatal neuron assay and a PC12-Exon-1 based assay. This compound was selected for testing in R6/2 mice, in which it was well-tolerated and showed a positive effect on body weight and a positive trend in preventing ventricular volume enlargment. These studies provide strong rationale for further testing the potential benefits of 3-hydroxy-3-trifluoromethylpyrazoles in treating HD.
- La Rosa, Salvatore,Benicchi, Tiziana,Bettinetti, Laura,Ceccarelli, Ilaria,Diodato, Enrica,Federico, Cesare,Fiengo, Pasquale,Franceschini, Davide,Gokce, Ozgun,Heitz, Freddy,Lazzeroni, Giulia,Luthi-Carter, Ruth,Magnoni, Letizia,Miragliotta, Vincenzo,Scali, Carla,Valacchi, Michela
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supporting information
p. 979 - 984
(2013/10/22)
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- Metal and boron derivatives of fluorinated cyclic 1,3-dicarbonyl compounds
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Starting from the corresponding cyclic 1,3-diketones or other precursors (cyclic ketones as well as lactones), several new salts and chelate complexes of fluorinated 1,3-dicarbonyls were obtained. Their preparative significance was demonstrated by straigh
- Sevenard, Dmitri V.,Khomutov, Oleg G.,Boltachova, Nadezhda S.,Filyakova, Vera I.,Vogel, Vera,Lork, Enno,Vyacheslav Ya. Sosnovskikh,Iaroshenko, Viktor O.,Roeschenthalerc, Gerd-Volker
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experimental part
p. 541 - 550
(2009/09/07)
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- The structure of fluorinated indazoles: The effect of the replacement of a H by a F atom on the supramolecular structure of NH-indazoles
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The structures of three NH-indazoles (3-methyl, 3-trifluoromethyl and 3-trifluoromethyl-4,5,6,7-tetrafluoroindazoles) have been determined by X-ray crystallography. These three compounds, together with 3-methyl-4,5,6,7- tetrafluoroindazole, whose X-ray st
- Teichert, Johannes,Oulie, Pascal,Jacob, Kane,Vendier, Laure,Etienne, Michel,Claramunt, Rosa M.,Lopez, Concepcion,Perez Medina, Carlos,Alkorta, Ibon,Elguero, Jose
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p. 936 - 946
(2008/02/12)
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- 'Through-Space' Hydrogen-Fluorine, Carbon-Fluorine and Fluorine-Fluorine Spin-Spin Coupling in 2-Phenyl-3-alkyl-4,5,6,7-tetrahydroindazoles
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1H, 13C and 19F NMR experiments for a series of 3-alkyl-2-phenyl-4,5,6,7-tetrahydroindazoles revealed a six-bond through-space coupling between the ortho-fluorine and the hydrogen or fluorine atom of the position 3-alkyl group.This was further supported b
- Lyga, John W.,Henrie, Robert N.,Meier, Gary A.,Creekmore, R. William,Patera, Russell M.
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p. 323 - 328
(2007/10/02)
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