cas 923604-59-5, Simeprevir | Articles data

Articles about 923604-59-5Total 5 be found

HCV inhibitors of HCV inhibitors and intermediates prepared by the method of
The invention relates to the drug synthesis technical field, specifically discloses compounds represented by the formula IV and the formula V and used for preparation of an HCV inhibitor Simeprevir and a preparation method thereof, and at the same time, also discloses a method for preparation of the HCV inhibitor Simeprevir with the compounds. In the process of preparation of the HCV inhibitor Simeprevir, during synthesis of a 14-membered macro ring, an amidation reaction is adopted for replacing a conventional double decomposition reaction, and the efficiency of the amidation reaction is much higher than that of the double decomposition reaction, and a step of synthesis of olefins is carried out in advance, so that the reaction steps of the whole synthesis are greatly shortened in the synthetic process, the operations are simple, expensive hydroxyl cycloglutaric acid and heterocyclic phenol have no need of consumption, and the production cost is greatly reduced.
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Paragraph 0058; 0059

(2019/06/11)

Ring-Closing Metathesis on Commercial Scale: Synthesis of HCV Protease Inhibitor Simeprevir
The key macrocyclization step in the synthesis of simeprevir, a hepatitis C virus (HCV) antiviral drug, was studied. N-Boc substitution on the diene precursor changes the site of insertion of the metathesis catalyst and, consequently, the kinetic model of the ring closing metathesis (RCM), enabling a further increase in the macrocyclization efficiency under simulated high dilution (SHD) conditions. NMR of the inserted species of both first and second generation RCM catalysts are reported and discussed.
Horváth, András,Depre, Dominique,Vermeulen, Wim A. A.,Wuyts, Stijn L.,Harutyunyan, Syuzanna R.,Binot, Grégori,Cuypers, Jef,Couck, Wouter,Den Heuvel, Dirk Van
p. 4932 - 4939
(2019/04/30)

POLYMORPHIC FORMS OF A MACROCYCLIC INHIBITOR OF HCV
Provided are crystalline forms of the compound of formula (I), which is a macrocyclic inhibitor of HCV, processes for the preparation thereof, and pharmaceutical compositions comprising these crystalline forms.
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Page/Page column 33-34

(2008/12/07)

Structure-activity relationship study on a novel series of cyclopentane-containing macrocyclic inhibitors of the hepatitis C virus NS3/4A protease leading to the discovery of TMC435350
SAR analysis performed with a limited set of cyclopentane-containing macrocycles led to the identification of N-[17-[2-(4-isopropylthiazole-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]- 13-methyl-2,14-dioxo-3,13-diazatricyclo [13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)sulfonamid e (TMC435350, 32c) as a potent inhibitor of HCV NS3/4A protease (Ki = 0.36 nM) and viral replication (replicon EC50 = 7.8 nM). TMC435350 also displayed low in vitro clearance and high permeability, which were confirmed by in vivo pharmacokinetic studies. TMC435350 is currently being evaluated in the clinics.
Raboisson, Pierre,de Kock, Herman,Rosenquist, Asa,Nilsson, Magnus,Salvador-Oden, Lourdes,Lin, Tse-I,Roue, Natalie,Ivanov, Vladimir,Waehling, Horst,Wickstroem, Kristina,Hamelink, Elizabeth,Edlund, Michael,Vrang, Lotta,Vendeville, Sandrine,Van de Vreken, Wim,McGowan, David,Tahri, Abdellah,Hu, Lili,Boutton, Carlo,Lenz, Oliver,Delouvroy, Frederic,Pille, Geert,Surleraux, Dominique,Wigerinck, Piet,Samuelsson, Bertil,Simmen, Kenneth
scheme or table
p. 4853 - 4858
(2009/05/11)

MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS
Inhibitors of HCV replication of formula (I) and the N-oxides, salts, and stereoisomers, wherein each dashed line represents an optional double bond; X is N, CH and where X bears a double bond it is C; R1 is -OR7, -NH-SO2R8; R2 is hydrogen, and where X is C or CH, R2 may also be C1-6alkyl; R3 is hydrogen, C1-6alkyl, C1-6alkoxyC1-6alkyl, C3-7cycloalkyl; R4 is aryl or Het; n is 3, 4, 5, or 6; R5 is halo, C1-6alkyl, hydroxy, C1-6alkoxy, phenyl, or Het; R6 is C1-6alkoxy, or dimethylamino; R7 is hydrogen; aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; R8 is aryl; Het; C3-7cycloalkyl optionally substituted with C1-6alkyl; or C1-6alkyl optionally substituted with C3-7cycloalkyl, aryl or with Het; aryl is phenyl optionally substituted with one, two or three substituents; Het is a 5 or 6 membered saturated, partially unsaturated or completely unsaturated heterocyclic ring containing 1 to 4 heteroatoms selected from nitrogen, oxygen and sulfur, and being optionally substituted with one, two or three substituents ; pharmaceutical compositions containing compounds (I) and processes for preparing compounds (I). Bioavailable combinations of the inhibitors of HCV of formula (I) with ritonavir are also provided.
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Page/Page column 76-77

(2008/06/13)