- CALPAIN MODULATORS AND METHODS OF PRODUCTION AND USE THEREOF
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The present technology relates to compounds, kits, compositions, and methods useful for the treatment of fibrotic disease. In some aspects, the present technology provides for treatment of various diseases or disorders associated or mediated, at least in part, by calpains, such as CAPN1, CAPN2, and/or CAPN9. The present technology is generally applicable to compounds which inhibit myofibroblast differentiation.
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- Synthesis method of (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate
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The invention belongs to the technical field of preparation of anti hepatitis C virus drug intermediates and particularly relates to a synthesis method of (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate. The synthesis method comprises the specific steps that step one, benzaldehyde, glycine ethyl ester hydrochloride, toluene and triethylamine are used as raw materials to be synthesized into a compound 4; step two, the compound 4 and trans-1,4-dibromo butene react in the toluene and sodium ethoxide to prepare a compound 3; step three, the compound 3 and (2S)-2-[(3,5-dichlorobenzoyl peroxide) oxy] propionic acid react in the toluene, and then isopropyl alcohol and hexane are added to obtain a compound 2; step four, the compound 2 reacts with sodium hydroxide in the toluene to obtain a compound (1R, 2S)-1-amino-2-vinyl ethyl cyclopropane dicarboxylate. The synthesis method is simple in operation and suitable for industrialized production, the raw materials are cheap and easy to obtain, and the obtained target product is high in purity and chiral purity.
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Paragraph 0018; 0019; 0020; 0021
(2016/10/09)
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- Macrocyclic compounds for suppressing replication of hepatitis C virus
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A compound as represented by Formula (I) is provided, wherein groups are defined in the description. The compound is used as HCV protease inhibitor for treating HCV infection.
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Page/Page column 39; 40
(2016/05/24)
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- Synthesis of bis-macrocyclic HCV protease inhibitor mk-6325 via intramolecular sp 2- sp 3 Suzuki-Miyaura coupling and ring closing metathesis
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A practical asymmetric synthesis of the complex fused bis-macrocyclic HCV protease inhibitor MK-6325 (1) is described. Through the combination of a high yielding and low catalyst loading ring-closing metathesis (RCM) to forge the 15-membered macrocycle with an intramolecular sp2-sp3 Suzuki-Miyaura cross-coupling to append the 18-membered macrocycle, multikilogram access to the unique and challenging architecture of MK-6325 (1) has been achieved.
- Li, Hongmei,Scott, Jeremy P.,Chen, Cheng-Yi,Journet, Michel,Belyk, Kevin,Balsells, Jaume,Kosjek, Birgit,Baxter, Carl A.,Stewart, Gavin W.,Wise, Christopher,Alam, Mahbub,Song, Zhiguo Jake,Tan, Lushi
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supporting information
p. 1533 - 1536
(2015/03/30)
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- Dynamic kinetic resolution of dehydrocoronamic acid
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Dehydrocoronamic acid can be racemised by dehydration of an N-acyl derivative to an azlactone, which undergoes facile racemisation. For the N-trifluoroacetyl derivative, the racemisation process was combined with an enzymatic resolution, to achieve a dynamic kinetic resolution process by which the racemate can be converted to either enantiomer. This journal is the Partner Organisations 2014.
- Chaplin, David A.,Fox, Martin E.,Kroll, Sebastian H. B.
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supporting information
p. 5858 - 5860
(2014/05/20)
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- METHOD FOR PRODUCING 1-AMINO-1-ALKOXYCARBONYL-2-VINYLCYCLOPROPANE
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It is an object of the present invention to provide a novel method for producing (1R,2S)/(1S,2R)-1-amino-1-alkoxycarbonyl-2-vinylcyclopropane which is useful as a synthetic intermediate of therapeutic agents for hepatitis C and a synthetic intermediate thereof. According to the present invention, when a trans-2-butene derivative having a leaving group at each of the 1- and 4-positions is reacted with a malonic ester in the presence of a base, a specific amount of an alkali metal alkoxide or an alkali metal hydride is used as the base, and further a specific amount of a malonic ester is used to produce a cyclopropane diester, and further, chiral or achiral 1-amino-1-alkoxy-carbonyl-2-vinylcyclopropane and a salt thereof are synthesized using the cyclopropane diester.
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Page/Page column 31
(2013/02/28)
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- ENZYMES AND METHODS FOR RESOLVING AMINO VINYL CYCLOPROPANE CARBOXYLIC ACID DERIVATIVES
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Preparation and isolation of amino vinyl cyclopropane carboxylic acid derivatives and salts thereof, methods of resolving enantiomers, and methods of identifying compositions and/or enzymes that are capable of resolving racemic or partially enantiomerically enriched mixtures.
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Page/Page column 13
(2011/02/24)
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- HCV PROTEASE INHIBITORS
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Novel compounds that are potent inhibitors of hepatitis C virus protease are provided. Pharmaceutical compositions containing one or more of these inhibitors, methods of preparing the inhibitors and methods of using the inhibitors to treat hepatitis C and related disorders also are provided.
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Page/Page column 36; 44
(2010/04/03)
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- Hepatitis C Virus Inhibitors
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Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 23
(2009/12/02)
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- UREA-CONTAINING PEPTIDES AS INHIBITORS OF VIRAL REPLICATION
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The invention provides compounds urea-containing peptide compounds of Formula I and the pharmaceutically salts and hydrates thereof. The variables T, R1-R9, J, L, M, Y, Z, m, n, and t are defined herein. Certain compounds of Formula
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- Process for the preparation of a macrocycle
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The present invention relates to a new process for the preparation of macrocyclic HCV protease inhibitor compounds of the formula wherein R1 is an amino protecting group and X is halogen by way of a ring closing metathesis approach.
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Page/Page column 11
(2009/07/10)
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- Inhibitors of Hepatitis C Virus
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Macrocyclic peptides are disclosed having the general formula: wherein R3, R3′, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 20
(2008/12/04)
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- Inhibitors of Hepatitis C Virus
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Macrocyclic peptides are disclosed having the general formula: wherein R3, R3′, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 19
(2008/12/04)
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- Inhibitors of Hepatitis C Virus
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Macrocyclic peptides are disclosed having the general formula: wherein R3, R′3, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 20
(2008/12/04)
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- Hepatitis C Virus Inhibitors
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Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 21-22
(2008/06/13)
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- Process for the preparation of macrocyclic compounds
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The present invention relates to a new process for the preparation of diene compounds of the formula I wherein R1 is an amino protecting group and X is a halogen atom which may serve as intermediates for the manufacture of macrocyclic HCV protease inhibitors.
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Page/Page column 6
(2008/12/04)
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- MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
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Macrocyclic peptides having the general formula (I): are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 38-39
(2008/12/05)
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- MACROCYCLIC PEPTIDES AS HEPATITIS C VIRUS INHIBITORS
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Macrocyclic peptides having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 37-38
(2008/12/05)
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- Hepatitis C Virus Inhibitors
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Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 32
(2008/12/05)
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- Hepatitis C virus inhibitors
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Macrocyclic peptides are disclosed having the general formula: wherein R′, R3, R3′, R4, R6, X, Q, and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 24
(2010/11/26)
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- Hepatitis C virus inhibitors
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Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 35
(2010/11/26)
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- Hepatitis C virus inhibitors
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The present disclosure relates to tripeptide 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.
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Page/Page column 37
(2008/06/13)
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- Hepatitis C virus inhibitors
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The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which inhibit the function of the NS3 protease (also referred to herein as “serine protease”) encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS3 protease.
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Page/Page column 35-36
(2008/06/13)
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- Epimerization reaction of a substituted vinylcyclopropane catalyzed by ruthenium carbenes: Mechanistic analysis
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A novel ruthenium carbene-catalyzed epimerization of vinylcyclopropanes is reported. The reaction rate strongly depends on the presence of ruthenium ligands in solution. When the first-generation Grubbs catalyst is employed, a 5.3:1 equilibrium ratio of epimers is established quickly, but when a first-generation Hoveyda catalyst is employed, epimerization is observed only if an additional phosphine or nitrogen ligand is added. NMR and kinetic studies suggest that the isomerization reaction occurs through the intermediacy of a ruthenacyclopentene. The observation suggests that cyclopropylmethylidene ruthenium carbenes of synthetic utility may be accessible via ruthenacyclopentenes obtained via other routes.
- Zeng, Xingzhong,Wei, Xudong,Farina, Vittorio,Napolitano, Elio,Xu, Yibo,Zhang, Li,Haddad, Nizar,Yee, Nathan K.,Grinberg, Nelu,Shen, Sherry,Senanayake, Chris H.
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p. 8864 - 8875
(2007/10/03)
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- HEPATITIS C VIRUS INHIBITORS
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Hepatitis C virus inhibitors are disclosed having the general formula (I) wherein A, R2, R3, R', B and Y are described in the description. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 62-63
(2010/02/11)
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- HEPATITIS C VIRUS INHIBITORS
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Compounds are disclosed having general formula (I), wherein R1, R2, R3, R4, R', B, Y and X are described in the description. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
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Page/Page column 62
(2010/02/11)
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- Synthesis of (1R,2S)-1-amino-2-vinylcyclopropanecarboxylic acid vinyl-ACCA derivatives: Key intermediates for the preparation of inhibitors of the hepatitis C virus NS3 protease
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(1R,2S)-1-Amino-2-vinylcyclopropanecarboxylic acid (vinyl-ACCA) is a key building block in the synthesis of potent inhibitors of the hepatitis C virus NS3 protease such as BILN 2061, which was recently shown to dramatically reduce viral load after administration to patients infected with HCV genotype 1. We have developed a scalable process that delivers derivatives of this unusual amino acid in >99% ee. The strategy was based on the dialkylation of a glycine Schiff base using trans-1,4-dibromo-2-butene as an electrophile to produce racemic vinyl-ACCA, which was subsequently resolved using a readily available, inexpensive esterase enzyme (Alcalase 2.4L). Factors that affect diastereoselection in the initial dialkylation steps were examined and the conditions optimized to deliver the desired diastereomer selectively. Product inhibition, which was encountered during the enzymatic resolution step, initially resulted in prolonged cycle times. Enrichment of racemic vinyl-ACCA through a chemical resolution via diastereomeric salt formation or the use of forcing conditions in the enzymatic reaction both led to improvements in throughput and the development of a viable process. The chemistry described herein was scaled up to produce multikilogram quantities of this building block.
- Beaulieu, Pierre L.,Gillard, James,Bailey, Murray D.,Boucher, Colette,Duceppe, Jean-Simon,Simoneau, Bruno,Wang, Xiao-Jun,Zhang, Li,Grozinger, Karl,Houpis, Ioannis,Farina, Vittorio,Heimroth, Heidi,Krueger, Thomas,Schnaubelt, Juergen
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p. 5869 - 5879
(2007/10/03)
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- Hepatitis C virus inhibitors
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The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
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- Substituted cycloalkyl P1' hepatitis C virus inhibitors
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The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
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Page/Page column 22
(2010/02/06)
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- HETEROCYCLICSULFONAMIDE HEPATITIS C VIRUS INHIBITORS
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The present invention relates to tripeptide compounds, compositionscontaining such compounds and methods for using such compounds for the treatment of heptitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositionscontaining such analogs and methods for using these analogs in the treatment of HCV infection.
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- Hepatitis C virus inhibitors
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The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
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- Regio- and diastereoselective synthesis of cyclic amino esters
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Several cyclic amino esters have been prepared regio- and diastereoselectively depending on the electrophile (cis or trans alkene) and its leaving group.
- Park, Kyung-Ho,Kurth, Thomas M.,Olmstead, Marilyn M.,Kurth, Mark J.
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p. 991 - 992
(2007/10/03)
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- Diastereoselective Solid-Phase Synthesis of Novel Hydantoin- and Isoxazoline-Containing Heterocycles
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Exploiting 1,3-dipolar cycloaddition and carbanilide cyclization transformations, we have prepared novel spirocyclic isoxazoloimidazolidinedione heterocycles of generalized structures II and III on solid phase starting from Merrifield resin. Cyclopentanoid isoxazoloimidazolidinedione II was obtained with complete diastereoselectivity, and cyclopropanoid isoxazoloimidazolidinedione III was obtained as an ≈ 2:1 mixture of diastereomers.
- Park, Kyung-Ho,Olmstead, Marilyn M.,Kurth, Mark J.
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p. 6579 - 6585
(2007/10/03)
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