- Redesigning of the cap conformation and symmetry of the diphenylethyne core to yield highly potent pan-genotypic NS5A inhibitors with high potency and high resistance barrier
-
Herein, we report the discovery of several NS5A inhibitors with potency against HCV genotype 1b in the picomolar range. Compounds (15, 33) were of extremely high potency against HCV genotype 1b (EC50 ≈ 1 pM), improved activity against genotype 3a (GT 3a) and good metabolic stability. We studied the impact of changing the cap conformation relative to the diphenylethyne core and/or compound symmetry on both potency and metabolic stability. The analogs obtained exhibited improved potency against HCV genotypes 1a, 1b, 3a and 4a compared to the clinically approved candidate daclatasvir with EC50 values in the low picomolar range and SI50s > 7 orders of magnitude. Compound 15, a symmetrically m-, m’-substituted diphenyl ethyne analog, was 150-fold more potent than daclatasvir against GT 3a, while compound 33, an asymmetrically m-, p-substituted diphenyl ethyne analog, was 35-fold more potent than daclatasvir against GT 3a. In addition, compound 15 exhibited a higher resistance barrier than daclatasvir against genotype 1b.
- Abadi, Ashraf H.,Abdallah, Mennatallah,Abdel-Halim, Mohammad,Bartenschlager, Ralf,Frakolaki, Efseveia,Hamed, Mostafa M.,Hirsch, Anna K. H.,Katsamakas, Sotirios,Vassilaki, Niki,Zoidis, Grigoris
-
-
- Preparation process of amino acid N-carboxylic acid anhydride
-
The invention provides a preparation process of amino acid N-carboxylic acid anhydride, which comprises the following operations: amino acid and methyl chloroformate are used as starting raw materials to react under an alkaline condition to generate N-methoxycarbonyl-amino acid, and the N-methoxycarbonyl-amino acid is separated and purified under an acidic condition; dissolving the purified and dried N-methoxycarbonyl-amino acid in a solvent, mixing with a ring closing reagent thionyl chloride, and reacting at a certain reaction temperature to generate an amino acid N-carboxylic acid anhydride crude product; and adding a good solvent into the obtained amino acid N-carboxylic acid anhydride crude product, filtering to remove impurities, adding a poor solvent into the filtrate, recrystallizing under freezing, and drying to obtain the amino acid N-carboxylic acid anhydride (NCA). The preparation process is simple and convenient in method, easy to purify, stable in process, controllable in quality, low in anhydrous requirement on a reaction system, greatly improved in product yield, greatly reduced in reaction risk and suitable for industrial mass production.
- -
-
Paragraph 0050-0053
(2021/06/06)
-
- Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors
-
Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.
- Mousa, Mai H. A.,Ahmed, Nermin S.,Schwedtmann, Kai,Frakolaki, Efseveia,Vassilaki, Niki,Zoidis, Grigoris,Weigand, Jan J.,Abadi, Ashraf H.
-
-
- NOVEL BENZIMIDAZOLE DERIVATIVES
-
The present invention discloses compounds of Formula (I), or pharmaceutically acceptable salts, esters, or prodrugs thereof: which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
-
Paragraph 0409
(2020/01/22)
-
- Compounds for inhibiting HCV (hepatitis C virus), pharmaceutical composition and application of compounds or pharmaceutical composition
-
The invention discloses compounds for inhibiting HCV (hepatitis C virus), pharmaceutical composition and an application of the compounds or the pharmaceutical composition. The compounds are compoundsshown in formula (I) or a stereoisomer, geometric isomer, a tautomer, an enantiomer, sulfur oxide, nitrogen oxide, hydrate, solvate, metabolite, pharmaceutically acceptable salt or prodrug of the compounds shown in formula (I); the compounds are effective antiviral drugs, especially can be used for inhibiting the function of NS5A protein encoded by the HCV, thereby effectively inhibiting the HCV.The method for preventing and/or treating drugs or diseases associated with the HCV by the compounds or the composition containing the new compounds has good market development prospects.
- -
-
Paragraph 0095; 0096; 0097
(2019/02/04)
-
- Monoglycosyl-containing heterocyclic compound for inhibiting hepatitis C viruses and preparation method
-
The invention discloses a monoglycosyl-containing heterocyclic compound for inhibiting hepatitis C viruses and a preparation method. The monoglycosyl-containing heterocyclic compound has a chemical structure represented by a formula I shown in the description. The monoglycosyl-containing heterocyclic compound disclosed by the invention can be used for effectively inhibiting protease of the hepatitis C viruses and treating infection of the hepatitis C viruses (HCV).
- -
-
Paragraph 0100-0103
(2019/03/28)
-
- A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus
-
A medicinal chemistry program based on the small-molecule HCV NS5A inhibitor daclatasvir has led to the discovery of dimeric phenylthiazole compound 8, a novel and potent HCV NS5A inhibitor. The subsequent SAR studies and optimization revealed that the cycloalkyl amide derivatives 27a-29a exhibited superior potency against GT1b with GT1b EC50 values at picomolar concentration. Interestingly, high diastereospecificity for HCV inhibition was observed in this class with the (1R,2S,1′R,2′S) diastereomer displaying the highest GT1b inhibitory activity. The best inhibitor 27a was found to be 3-fold more potent (GT1b EC50 = 0.003 nM) than daclatasvir (GT1b EC50 = 0.009 nM) against GT1b, and no detectable in vitro cytotoxicity was observed (CC50 > 50 μM). Pharmacokinetic studies demonstrated that compound 27a had an excellent pharmacokinetic profiles with a superior oral exposure and desired bioavailability after oral administration in both rats and dogs, and therefore it was selected as a developmental candidate for the treatment of HCV infection.
- Yeh, Teng-Kuang,Kang, Iou-Jiun,Hsu, Tsu-An,Lee, Yen-Chun,Lee, Chung-Chi,Hsu, Sheng-Ju,Tian, Ya-Wen,Yang, Hui-Yun,Chen, Chiung-Tong,Chao, Yu-Sheng,Yueh, Andrew,Chern, Jyh-Haur
-
p. 245 - 268
(2019/02/19)
-
- 5,5-FUSED ARYLENE OR HETEROARYLENE HEPATITIS C VIRUS INHIBITORS
-
Provided herein are 5,5-fused heteroarylene hepatitis C virus inhibitor compounds, for example, of Formula I, IA, or IB, pharmaceutical compositions comprising the compounds, and processes of preparation thereof. Also provided are methods of their use for the treatment of an HCV infection in a host in need thereof.
- -
-
Paragraph 0233
(2018/08/20)
-
- Highlights of the Structure-Activity Relationships of Benzimidazole Linked Pyrrolidines Leading to the Discovery of the Hepatitis C Virus NS5A Inhibitor Pibrentasvir (ABT-530)
-
Curative interferon and ribavirin sparing treatments for hepatitis C virus (HCV)-infected patients require a combination of mechanistically orthogonal direct acting antivirals. A shared component of these treatments is usually an HCV NS5A inhibitor. First generation FDA approved treatments, including the component NS5A inhibitors, do not exhibit equivalent efficacy against HCV virus genotypes 1-6. In particular, these first generation NS5A inhibitors tend to select for viral drug resistance. Ombitasvir is a first generation HCV NS5A inhibitor included as a key component of Viekira Pak for the treatment of patients with HCV genotype 1 infection. Since the launch of next generation HCV treatments, functional cure for genotype 1-6 HCV infections has been achieved, as well as shortened treatment duration across a wider spectrum of genotypes. In this paper, we show how we have modified the anchor, linker, and end-cap architecture of our NS5A inhibitor design template to discover a next generation NS5A inhibitor pibrentasvir (ABT-530), which exhibits potent inhibition of the replication of wild-type genotype 1-6 HCV replicons, as well as improved activity against replicon variants demonstrating resistance against first generation NS5A inhibitors.
- Wagner, Rolf,Randolph, John T.,Patel, Sachin V.,Nelson, Lissa,Matulenko, Mark A.,Keddy, Ryan,Pratt, John K.,Liu, Dachun,Krueger, A. Chris,Donner, Pamela L.,Hutchinson, Douglas K.,Flentge, Charles,Betebenner, David,Rockway, Todd,Maring, Clarence J.,Ng, Teresa I.,Krishnan, Preethi,Pilot-Matias, Tami,Collins, Christine,Panchal, Neeta,Reisch, Thomas,Dekhtyar, Tatyana,Mondal, Rubina,Stolarik, Deanne F.,Gao, Yi,Gao, Wenqing,Beno, David A.,Kati, Warren M.
-
supporting information
p. 4052 - 4066
(2018/05/14)
-
- Sulfur(vi) fluoride exchange as a key reaction for synthesizing biaryl sulfate core derivatives as potent hepatitis C virus NS5A inhibitors and their structure-activity relationship studies
-
Extremely potent, new hepatitis C virus (HCV) nonstructural 5A (NS5A) featuring substituted biaryl sulfate core structures was designed and synthesized. Based on the previously reported novel HCV NS5A inhibitors featuring biaryl sulfate core structures which exhibit two-digit picomolar half-maximal effective concentration (EC50) values against HCV genotype 1b and 2a, the new inhibitors equipped with the sulfate core structures containing diversely substituted aryl groups were explored. In this study, highly efficient, chemoselective coupling reactions between an arylsulfonyl fluoride and an aryl silyl ether, known as the sulfur(vi) fluoride exchange (SuFEx) reaction, were utilized. Among the inhibitors prepared based on the SuFEx chemistry, compounds 14, 15 and 29 exhibited two-digit picomolar EC50 values against GT-1b and single digit or sub nanomolar activities against the HCV GT-2a strain. Nonsymmetrical inhibitors containing an imidazole and amide moieties on each side of the sulfate core structures were also synthesized. In addition, a biotinylated probe targeting NS5A protein was prepared for labeling using the same synthetic methodology.
- You, Youngsu,Kim, Hee Sun,Park, Jung Woo,Keum, Gyochang,Jang, Sung Key,Kim, B. Moon
-
p. 31803 - 31821
(2018/09/25)
-
- HEPATITIS C VIRUS INHIBITORS AND USES THEREOF IN PREPARATION OF DRUGS
-
A series of hepatitis C virus (HCV) inhibitors and compositions and applications thereof in the preparation of drugs for treating chronic HCV infection. Especially, a series of compounds that are used as NS5A inhibitors, and compositions and uses thereof in the preparations of drugs.
- -
-
Paragraph 0227; 0228
(2017/12/17)
-
- New potent biaryl sulfate-based hepatitis C virus inhibitors
-
The discovery of a new series of potent hepatitis C virus (HCV) NS5A inhibitors containing biaryl sulfone or sulfate cores is reported. Structure-activity relationship (SAR) studies on inhibitors containing various substitution patterns of the sulfate or sulfone core structure established that m-,m′- substituted biaryl sulfate core-based inhibitors containing an amide moiety (compound 20) or an imidazole moiety (compound 24) showed extremely high potency. Compound 20 demonstrated double-digit pM potencies against both genotype 1b (GT-1b) and 2a (GT-2a). Compound 24 also exhibited double-digit pM potencies against GT-1b and sub nM potencies against GT-2a. Furthermore, compounds 20 and 24 exhibited no cardiotoxicity in an hERG ligand binding assay and showed acceptable plasma stability and no mutagenic potential in the Ames test. In addition, these compounds showed distinctive additive effects in combination treatment with the NS5B targeting drug sofosbuvir (Sovaldi). The results of this study showed that the compounds 20 and 24 could be effective HCV inhibitors.
- You, Youngsu,Kim, Hee Sun,Bae, Il Hak,Lee, Seung Gi,Jee, Min Hyeok,Keum, Gyochang,Jang, Sung Key,Kim, B. Moon
-
-
- Diphenyl sulfate derivatives or pharmaceutically acceptable salts thereof, preparation method thereof and pharmaceutical composition for use in preventing or treating hepatitis C virus related diseases
-
The present invention relates to a diphenyl sulfate derivative or a pharmaceutically acceptable salt thereof, a production method thereof, and a pharmaceutical composition for preventing or treating hepatitis C virus-associated diseases containing the same as an active ingredient. According to the present invention, the diphenyl sulfate derivative excellently inhibits infection by hepatitis C virus and replication of hepatitis C virus, and thus can be useful as pharmaceutical compositions for preventing or treating liver diseases such as hepatocellular cancer, cirrhosis, chronic hepatitis C, and acute hepatitis C caused by hepatitis C virus.COPYRIGHT KIPO 2017
- -
-
Paragraph 0165-0167
(2017/05/23)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Paragraph 0415-0416
(2017/07/05)
-
- BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS
-
The disclosed compounds have antiviral activity against C-type virus, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating liver disease caused by hepatitis C virus. The benzidine derivative according to the present invention has excellent antiviral activity against hepatitis C virus and exhibits excellent medicinal activity in the living body, and thus the pharmaceutical composition containing the same as an active ingredient can be useful as a pharmaceutical composition for preventing or treating liver disease, such as acute hepatitis C, chronic hepatitis C, cirrhosis, or hepatocellular carcinoma, caused by C-type virus.
- -
-
Paragraph 0156; 0157; 0158
(2016/02/24)
-
- A N-methoxycarbonyl group-L-valine synthesizing method (by machine translation)
-
The invention discloses a N-methoxycarbonyl group-L-valine synthesizing method, comprising the following steps: adding methanol or ethanol in the reaction kettle, adding L-valine and triethylamine, to the reaction after the temperature rise, methyl formate in the cauldron adds by drops the chlorine, after the reaction end, reduced pressure distillation is condensed to water slurry is added, using hydrochloric acid or phosphoric acid adjusted to pH 1.0 the [...] 2.0, product is obtained by crystallization separation. This invention the reaction temperature is relatively mild, the safety factor is low, the environmental protection, the cost is low. (by machine translation)
- -
-
Paragraph 0013; 0025; 0026
(2016/11/02)
-
- SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
-
Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
- -
-
Page/Page column 0271
(2015/11/09)
-
- ANTI-VIRAL COMPOUND
-
The present invention features crystalline forms of Compound I.
- -
-
Paragraph 0023
(2015/11/27)
-
- NOVEL INHIBITORS OF HEPATITIS C VIRUS
-
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0142; 0143
(2015/09/22)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present invention discloses compounds of Formula (I), and pharmaceutically acceptable salts, esters, or prodrugs thereof: (structurally represented), which inhibit RNA-containing virus, particularly the hepatitis C virus (HCV). Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.
- -
-
Page/Page column 61
(2015/02/25)
-
- Potent hepatitis C virus NS5A inhibitors containing a benzidine core
-
Here we report the discovery of a series of potent hepatitis C virus (HCV) NS5A inhibitors based on the benzidine prolinamide backbone. Taking a simple synthetic route, we developed a novel inhibitor structure, which allows easy modification, and through optimization of the capping group, we identified compound 6 with highly potent anti-HCV activity. Compound 6 is nontoxic and is anticipated to be an effective HCV drug candidate.
- Bae, Il Hak,Choi, Jin Kyu,Chough, Chieyeon,Keum, Sun Ju,Kim, Heesun,Jang, Sung Key,Kim, B. Moon
-
supporting information
p. 255 - 258
(2014/04/03)
-
- HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0296; 0297
(2013/05/21)
-
- HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formulas (I) or (II): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0248; 0249
(2013/11/06)
-
- PIPERAZINE-PIPERIDINE COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
Paragraph 0258; 0259
(2013/11/06)
-
- NOVEL HEPATITIS C VIRUS INHIBITORS
-
The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
- -
-
Page/Page column 33
(2013/07/05)
-
- SILYL-CONTAINING HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to novel Silyl-Containing Heterocyclic Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, B, C, D, E, F and L are as defined herein. The present invention also relates to compositions comprising at least one Silyl-Containing Heterocyclic Compound, and methods of using the Silyl-Containing Heterocyclic Compounds for treating or preventing HCV infection in a patient.
- -
-
Page/Page column 62
(2013/03/28)
-
- SILYL-CONTAINING HETEROCYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to novel Silyl-Containing Heterocyclic Compounds of Formula (I): (I) and pharmaceutically acceptable salts thereof, wherein A, B, C, D and R2 are as defined herein. The present invention also relates to compositions comprising at least one Silyl-Containing Heterocyclic Compound, and methods of using the Silyl-Containing Heterocyclic Compounds for treating or preventing HCV infection in a patient.
- -
-
Page/Page column 58
(2013/03/28)
-
- PROCESSES FOR THE PREPARATION OF NOVEL BENZIMIDAZOLE DERIVATIVES
-
The present invention relates to processes and intermediates for the preparation of novel benzimidazole derivatives, especially in the synthesis of hepatits C virus NS5A inhibitors. In particular, the present invention relates to processes and intermediates for the preparation of compounds of formulae (I-a):
- -
-
Page/Page column 35; 36
(2013/05/09)
-
- Synthesis and in vitro evaluation of new derivatives of 2-substituted-6-fluorobenzo[d]thiazoles as cholinesterase inhibitors
-
A series of novel cholinesterase inhibitors based on 2-substituted 6-fluorobenzo[d]thiazole were synthesised and characterised by IR, 1H, 13C and 19F NMR spectroscopy and HRMS. Purity was checked by elemental analyses. The novel carbamates were tested for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The toxicity of the most active compounds was investigated using a standard in vitro test with HepG2 cells, and the ratio between biological activity and toxicity was determined. In addition, the toxicity of the most active compounds was evaluated against MCF7 cells using the xCELLigence system. Structure-activity relationships reflecting the dependence of cholinesterase inhibitors on the lipophilicity of the compounds as well as on the Taft polar and steric substituent constants are discussed. The specific orientation of the inhibitors in the binding site of acetylcholinesterase was determined using molecular docking of the most active compound.
- Imramovsky, Ale?,Pejchal, Vladimír,?těpánková, ?árka,Vor?áková, Katarína,Jampílek, Josef,Van?o, Ján,?im?nek, Petr,Královec, Karel,Br??ková, Lenka,Mandíková, Jana,Trejtnar, Franti?ek
-
p. 1735 - 1748
(2013/05/08)
-
- SOLID FORMS COMPRISING INHIBITORS OF HCV NS5A, COMPOSITIONS THEREOF, AND USES THEREWITH
-
This invention relates to: -a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) composition comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and composition; (e) method of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.
- -
-
Paragraph 0111
(2013/08/28)
-
- ANTI-VIRAL COMPOUNDS
-
Compounds effective in inhibiting replication of Hepatitis C virus ("HCV") are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.
- -
-
Page/Page column 152
(2012/06/30)
-
- TETRACYCLIC INDOLE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to novel Tetracyclic Indole Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, A', G, R1, R15, U, V, V', X, X', Y and Y' are as defined herein. The present invention also relates to compositions comprisingat least one Tetracyclic Indole Derivative, and methods of using the Tetracyclic Indole Derivatives for treating or preventing HCV infection in a patient.
- -
-
Page/Page column 70-71
(2012/04/17)
-
- FUSED TETRACYCLE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to novel Fused Tetracycle Derivatives of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, A', B, G, R1, U, V, W, W', X, X', Y and Y' are as defined herein. The present invention also relates to compositions comprising at least one Fused Tetracycle Derivative, and methods of using the Fused Tetracycle Derivatives for treating or preventing HCV infection in a patient.
- -
-
Page/Page column 70
(2012/05/04)
-
- TETRACYCLIC XANTHENE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
-
The present invention relates to novel Tetracyclic Xanthene Derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, Y1, Y2, Z, Ra, Rb, R1a, R1b and R2 are as defined herein. The present invention also relates to compositions comprising at least one Tetracyclic Xanthene Derivative, and methods of using the Tetracyclic Xanthene Derivatives for treating or preventing HCV infection in a patient.
- -
-
Page/Page column 33-34
(2012/10/07)
-
- TETRACYCLIC XANTHENE DERIVATIVES AND METHODS OF USE THEREOF FOR TREATMENT OF VIRAL DISEASES
-
The present invention discloses tetracyclic xanthene derivatives of Formula (I) and pharmaceutically acceptable salts thereof, wherein A, Y1, Y2, Z, Ra, Rb, R1a, R1b, and R2 are as defined herein. The present invention also discloses compositions comprising at least one tetracyclic xanthene derivative, and methods of using the tetracyclic xanthene derivatives for treating or preventing HCV infection in a patient.
- -
-
Page/Page column 52
(2012/10/07)
-
- ANTIVIRAL COMPOUNDS
-
The present invention provides compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 67
(2012/09/22)
-
- NOVEL INHIBITORS OF HEPATITIS C VIRUS
-
The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
- -
-
-
- HETERO-BICYCLIC DERIVATIVES AS HCV INHIBITORS
-
Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, hydrates, solvates thereof, wherein R and R' have the meaning as defined herein. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use, alone or in combination with other HCV inhibitors,in HCV therapy.
- -
-
Page/Page column 23
(2012/02/13)
-
- HEPATITIS C VIRUS INHIBITORS
-
The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.
- -
-
Page/Page column 65-66
(2012/02/15)
-
- TETRACYCLIC HETEROCYCLE COMPOUNDS FOR TREATING HEPATITIS C VIRAL INFECTION
-
Tetracyclic heterocycle compounds of formula (I) and pharmaceutically acceptable salts thereof are provided, wherein A, A', G, R1, R15, U, V, V', W, W, X, X', Y and Y' are as defined in the invention. The pharmaceutical compositions comprising these compounds and the use of the compounds for treating hepatitis C virus (HCV) infection are also provided.
- -
-
Page/Page column 63-64
(2012/04/17)
-
- TETRACYCLIC INDOLE DERIVATIVES FOR TREATING HEPATITIS C VIRUS INFECTION
-
Tetracyclic indole derivatives of formula (I), pharmaceutically acceptable salts and the pharmaceutical compositions thereof are provided, wherein A, A', G, R1, R15, U, V, V, W, W, X, X', Y, Y' are as defined in the invention. Use of these derivatives for treating hepatitis C virus (HCV) infection is also provided.
- -
-
Page/Page column 79-80
(2012/04/17)
-
- FUSED TETRACYCLIC HETEROCYCLE COMPOUNDS AND METHODS OF USE THEREOF FOR TREATMENT OF VIRAL DISEASES
-
The present invention discloses novel Fused Tetracyclic Heterocycle Compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein A, A', G, R1, R15, U, V, V', W, W', X, X', Y and Y' are as defined herein. The present invention also discloses compositions comprising at least one Fused Tetracyclic Heterocycle Compound, and methods of using the Fused Tetracyclic Heterocycle Compounds for treating or preventing HCV infection in a patient.
- -
-
-
- Benzimidazole-imidazole Derivatives
-
Inhibitors of HCV replication of formula I including stereochemically isomeric forms, and salts, solvates thereof, wherein R and R′ are, each independently, —CR1R2R3, aryl, heteroaryl or heteroC4-6cycloalkyl, whereby aryl and heteroaryl may optionally be substituted with 1 or 2 substituents selected from halo and methyl. The present invention also relates to processes for preparing said compounds, pharmaceutical compositions containing them and their use in HCV therapy.
- -
-
-
- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds
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- HEPATITIS C INHIBITOR COMPOUNDS
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Compounds of Formula (I) and (II) wherein R1, R2, R3, R6, A and A' are defined herein. The compounds are useful as inhibitors of the function of NS5A protein encoded by HCV for the treatment of hepatitis C viral infection.
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Page/Page column 31
(2012/05/04)
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- FUSED TRICYCLIC COMPOUNDS AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES
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The present invention relates to novel Fused Tricyclic Compounds, compositions comprising at least one Fused Tricyclic Compound, and methods of using Fused Tricyclic Compounds for treating or preventing a viral infection or a virus-related disorder in a patient.
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Page/Page column 72; 73
(2011/08/04)
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- BENZIMIDAZOLE-IMIDAZOLE DERIVATIVES
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Inhibitors of HCV replication of formula (I) including stereochemically isomeric forms, and salts, solvates thereof, wherein R and R' are, each independently,-CR1R2R3, aryl, heteroaryl or heteroC4-6cycloalkyl, whereby aryl and heteroaryl may optionally be substituted with 1 or 2 substituents selected from halo and methyl. 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 46-47
(2011/06/11)
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- BENZIMIDAZOLE ANALOGUES FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS
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Compounds represented by formula (I) or pharmaceutically acceptable salts and solvates thereof, wherein A, B, B', X, Y, R1, R1 ', R2, R2', R3, R3', R5, R5', R6, m, n, or p are as defined herein, are useful for treating flaviviridae viral infections.
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Page/Page column 346-347
(2011/02/24)
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- ANALOGUES FOR THE TREATMENT OR PREVENTION OF FLAVIVIRUS INFECTIONS
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Compounds represented by formula I as described herein or pharmaceutically acceptable salts thereof, wherein A, B, B', X, Y, R1, R2, R2', R3, R3', R4, R4', R5, R5', m, n, or p are as defined herein, are useful for treating flaviviridae viral infections.
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Page/Page column 127
(2011/10/13)
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