- Discovery of fused tricyclic core containing HCV NS5A inhibitors with pan-genotype activity
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HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein, we describe research efforts that led to the discovery of a series of fused tricyclic core containing HCV NS5A inhibitors such as 24, 39, 40, 43, and 44 which have pan-genotype activity and are orally bioavailable in the rat.
- Yu, Wensheng,Coburn, Craig A.,Yang, De-Yi,Meinke, Peter T.,Wong, Michael,Rosenblum, Stuart B.,Chen, Kevin X.,Njoroge, George F.,Chen, Lei,Dwyer, Michael P.,Jiang, Yueheng,Nair, Anilkumar G.,Selyutin, Oleg,Tong, Ling,Zeng, Qingbei,Zhong, Bin,Ji, Tao,Hu, Bin,Agrawal, Sony,Xia, Ellen,Zhai, Ying,Liu, Rong,Kong, Rong,Ingravallo, Paul,Asante-Appiah, Ernest,Nomeir, Amin,Fells, James,Kozlowski, Joseph A.
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p. 3158 - 3162
(2016/06/13)
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- FUSED TRICYCLIC COMPOUNDS AND USE THEREOF FOR TREATING VIRAL DISEASES
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Fused tricyclic compounds of formula (I) and pharmaceutically acceptable salts thereof are disclosed, wherein X1, X2, X3, X4, Y1, Y2, M1, M2, Ra, Rb, R1, R2 and R6 are as defined in the description. Compositions comprising at least one fused tricyclic compound and methods of using the fused tricyclic compounds for treating or preventing HCV infection in a patient are also disclosed.
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- ORDER OF THE REPLACEMENT OF HYDROGEN BY HALOGEN IN THE HALOGENATION OF DIBENZO-p-DIOXIN AND ITS NITRO AND AMINO DERIVATIVES
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The order of the replacement of hydrogen by halogen in the bromination and chlorination of dibenzo-p-dioxin and its nitro and amino derivatives was examined with the purpose of determining the possibilities of the formation of highly toxic isomers of halogenated dibenzo-p-dioxins from precursors with a tricyclic structure of dibenzo-p-dioxin.A number of halogenated dibenzo-p-dioxins were synthesized, which illustrates the order of the replacement, and their physicochemical and spectral characteristics are given.
- Kuntsevich, A. D.,Golovkov, V. F.,Chernov, S. A.
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p. 1279 - 1286
(2007/10/02)
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- Syntheses of dibenzodioxin derivatives via iron complexes, and further functionalizations via directed metallation
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Double nucleophilic aromatic substitution reactions between (cyclopentadienyl)(η6-1,2-dichlorobenzene)iron(1 +) salts and substituted 1,2-benzenediols have been carried out under mild conditions to prepare 6-dibenzodioxin>iron(1 +) complexes functionalized in the 1- or 2-position with an alkyl, aldehyde, carboxylic acid, methoxycarbonyl, carboxamide, or hydroxy group. 3-Methyl- and 4-methyl-(η6-1,2-dichlorobenzene)iron complexes were treated with substituted 1,2-benzenediols to effect functionalization of both aromatic rings of the heterocycle.The dibenzodioxin ligands were liberated routinely by irradiation with ultraviolet light.Directed deprotonation of the free functionalized dibenzodioxins with an alkyllithium reagent followed by quenching with a variety of electrophiles yielded further derivatives, including two new isoindolone systems.
- Cambie, Richard C.,Janssen, Sally J.,Rutledge, Peter S.,Woodgate, Paul D.
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p. 387 - 418
(2007/10/02)
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