- The First Kilogram Synthesis of Beclabuvir, an HCV NS5B Polymerase Inhibitor
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The process development and kilogram-scale synthesis of beclabuvir (BMS-791325, 1) is described. The convergent synthesis features the use of asymmetric catalysis to generate a chiral cyclopropane fragment and coupling with an indole fragment via an alkyl
- Bien, Jeffrey,Davulcu, Akin,Delmonte, Albert J.,Fraunhoffer, Kenneth J.,Gao, Zhinong,Hang, Chao,Hsiao, Yi,Hu, Wenhao,Katipally, Kishta,Littke, Adam,Pedro, Aghogho,Qiu, Yuping,Sandoval, Maria,Schild, Richard,Soltani, Michelle,Tedesco, Anthony,Vanyo, Dale,Vemishetti, Purushotham,Waltermire, Robert E.
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p. 1393 - 1408
(2018/09/06)
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- HEPATITIS B CORE PROTEIN MODULATORS
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The present disclosure provides, in part, compounds having allosteric effector properties against Hepatitis B virus Cp. Also provided herein are methods of treating viral infections, such as hepatitis B, comprising administering to a patient in need thereof a disclosed compound of formula:
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- An efficient process for the large-scale synthesis of a 2,3,6-trisubstituted indole
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The efficient synthesis of a key trisubstituted indole intermediate 1 is described. The synthetic route required the use of an aryl Grignard reagent which was not commercially available, and the large-scale formation of this fragment and the thermal evalu
- Alorati, Anthony D.,Gibb, Andrew D.,Mullens, Peter R.,Stewart, Gavin W.
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p. 1947 - 1952
(2013/03/14)
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- Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors
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The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.
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Page/Page column 48
(2010/09/05)
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- CYCLOPROPYL FUSED INDOLOBENZAZEPINE HCV NS5B INHIBITORS
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The invention encompasses compounds of formula (I) as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV
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Page/Page column 40-41
(2009/06/27)
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- AROMATIC HETEROCYCLIC FUSED INDOLOBENZADIAZEPINE HCV NS5B INHIBITORS
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The disclosure provides compounds of formula (I), including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 24-25
(2009/10/22)
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 25
(2009/05/28)
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 23
(2009/05/28)
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- MACROCYCLIC INDOLES AS HEPATITIS C VIRUS INHIBITORS
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The present invention relates to inhibitors of HCV replication of formula (I), the N-oxide forms, the pharmaceutically acceptable addition salts, the quaternary amines and the stereochemically isomeric forms thereof, formula (I), wherein R1; R3; and R4 have the meaning defined in the claims. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.
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Page/Page column 57
(2009/07/25)
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- Antiviral indoles
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Compounds of the formula (I): wherein A, B, D, M, Ar, W, X, Y, Z and R1 are as defined herein, are useful in the prevention and treatment of hepatitis C infections. The compounds, their preparation, pharmaceutical compositions containing them and their use in medicine are disclosed.
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Page/Page column 6-7
(2008/12/06)
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of Formula I, pharmaceutically acceptable salts thereof, compositions, and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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-
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 14
(2008/12/07)
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 33
(2008/12/07)
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 30
(2008/12/07)
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- Compounds for the Treatment of Hepatitis C
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The invention encompasses compounds of formula I, including pharmaceutically acceptable salts, as well as compositions and methods of using these compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 64
(2008/12/07)
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- Indolobenzazepine HCV NS5B inhibitors
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The invention encompasses compounds and salts of Formulas I, II, III, and IV as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 175
(2008/06/13)
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- Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors
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The invention encompasses compounds of Formula I, pharmaceutically acceptable salts thereof, compositions, and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 71-72
(2008/06/13)
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- Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 3; 32
(2008/06/13)
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- Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 16
(2008/06/13)
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- Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 21
(2008/06/13)
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- Cyclopropyl Fused Indolobenzazepine HCV NS5B Inhibitors
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The invention encompasses compounds of formula I as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV.
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Page/Page column 40
(2008/06/13)
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- TETRACYCLIC INDOLE DERIVATIVES AS ANTIVIRAL AGENTS
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The present invention relates to tetracyclic indole compounds of formula (I); wherein R1, R2, A, Ar, W, X, Y and Z are defined herein, and pharmaceutically acceptable salts thereof, pharmaceutical compositions comprising them, and their use for the treatment or prevention of infection by hepatitis C virus.
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Page/Page column 21; 24-25; 37; 64
(2010/11/08)
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- Improved replicon cellular activity of non-nucleoside allosteric inhibitors of HCV NS5B polymerase: From benzimidazole to indole scaffolds
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Benzimidazole-based allosteric inhibitors of the hepatitis C virus (HCV) NS5B polymerase were diversified to a variety of topologically related scaffolds. Replacement of the polar benzimidazole core by lipophilic indoles led to inhibitors with improved potency in the cell-based subgenomic HCV replicon system. Transposing the indole scaffold into a previously described series of benzimidazole-tryptophan amides generated the most potent inhibitors of HCV RNA replication in cell culture reported to date in this series (EC50 ~ 50 nM).
- Beaulieu, Pierre L.,Gillard, James,Bykowski, Darren,Brochu, Christian,Dansereau, Nathalie,Duceppe, Jean-Simon,Hache, Bruno,Jakalian, Araz,Lagace, Lisette,LaPlante, Steven,McKercher, Ginette,Moreau, Elaine,Perreault, Stephane,Stammers, Timothy,Thauvette, Louise,Warrington, Jeff,Kukolj, George
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p. 4987 - 4993
(2007/10/03)
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- Inhibitors of HCV replication
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Indole compounds of Formula I are described. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV. Different forms and compositions comprising the compounds are also described as well as methods of preparing the compounds.
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Page/Page column 18-19; 38
(2010/10/20)
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- INDOLE DERIVATIVES FOR TREATING VIRAL INFECTIONS
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Disclosed are compounds having formula I and related compositions and methods thereof. The compounds are useful for treating viral infections caused by the Flaviviridae family of viruses.
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Page/Page column 136
(2008/06/13)
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- INDOLE DERIVATIVES AS ANTIVIRAL AGENTS
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The present invention relates to indole compounds of the formula (I): wherein R1, R2, R3, R4, A, E and X are as defined herein, and pharmaceutically acceptable salts thereof, useful in the prevention and treatment of hepatitis C infections.
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Page/Page column 22
(2010/10/20)
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- Development and preliminary optimization of indole-N-acetamide inhibitors of hepatitis C virus NS5B polymerase
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Allosteric inhibition of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase enzyme has recently emerged as a viable strategy toward blocking replication of viral RNA in cell-based systems. We report here a novel class of allosteric inhibitor of NS5B that shows potent affinity for the NS5B enzyme and effective inhibition of subgenomic HCV RNA replication in HUH-7 cells. Inhibitors from this class have promising characteristics for further development as anti-HCV agents.
- Harper, Steven,Pacini, Barbara,Avolio, Salvatore,Di Filippo, Marcello,Migliaccio, Giovanni,Laufer, Ralph,De Francesco, Raffaele,Rowley, Michael,Narjes, Frank
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p. 1314 - 1317
(2007/10/03)
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- VIRAL POLYMERASE INHIBITORS
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An isomer, enantiomer, diastereoisomer or tautomer of a compound, represented by formula (I): wherein wherein A, B, R2, R3, L, M1, M2, M3, M4, Y1, Y0, Z and Sp are as defined in claim 1, or a salt thereof, as an inhibitor of HCV NS5B polymerase.
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- INDOLE ACETAMIDES AS INHIBITORS OF THE HEPATITIS C VIRUS NS5B POLYMERASE
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The present invention relates to indole and azaindole compounds of formula (I): wherein X1, X2, X3, X4, A1, Ar1, R1, R2 and n are as defined herein, and pharmaceutically acceptable salts thereof, useful in the prevention and treatment of hepatitis C infections.
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- Viral polymerase inhibitors
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An isomer, enantiomer, diastereoisomer, or tautomer of a compound, represented by formula I: wherein: A is O, S, NR1, or CR1, wherein R1 is defined herein; ---- represents either a single or a double bond; R2 is selected from: H, halogen, R21, OR21, SR21, COOR21, SO2N(R22)2, N(R22)2, CON(R22)2, NR22C(O)R22 or NR22C(O)NR22 wherein R21 and each R22 is defined herein; B is NR3 or CR3, with the proviso that one of A or B is either CR1 or CR3, wherein R3 is defined herein; K is N or CR4, wherein R4 is defined herein; L is N or CR5, wherein R5 has the same definition as R4 defined above; M is N or CR7, wherein R7 has the same definition as R4 defined above; Y1 is O or S; Z is N(R6a)R6 or OR6, wherein R6a is H or alkyl or NR61R62 wherein R61 and R62 are defined herein; a salt or a derivative thereof, as an inhibitor of HCV NS5B polymerase.
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