691852-58-1

Usage

Biological Activity

nesbuvir is a novel selective inhibitor of nonstructural protein 5b (ns5b) polymerase with ic50 value of 5 nm [1].ns5b (nonstructural protein 5b) is a viral protein found in hcv and plays an important role in hcv rna replicate by using the viral positive rna strand as its template and catalyzing the polymerization of rntp during rna replication. as the principal catalytic enzyme for hcv replication, ns5b is a viable target for hcv-rna replication and used as a target for hcv therapy [2] [3].nesbuvir is a selective ns5b polymerase inhibitor and has a different selectivity with the reported alk inhibitor crizotinib. when tested with huh7.5 cell line, nesbuvir showed the highest selectivity for ns5b and mutations reduced the cells susceptibility [1]. in clone a cells derived from huh-7 cells containing approximately 1,000 genome copies of hcv genotype 1b replicon per cell, nesbuvir treatment with the concentration of 0.1 and 1 μm for 16-day reduced about 3.6 log10 and 4.2 log10 hcv rna levels, respectively [2].in the chimeric mouse model, nesbuvir treatment resulted in a 2.02 +/- 0.55 log reduction in hcv titer, whereas in combination with interferon using a suboptimal dose of 30 mg/kg three times per day showed a 2.44 log reduction and were better than interferon treatment only [4].

references

[1]. flint, m., et al., selection and characterization of hepatitis c virus replicons dually resistant to the polymerase and protease inhibitors hcv-796 and boceprevir (sch 503034). antimicrob agents chemother, 2009. 53(2): p. 401-11.[2]. howe, a.y., et al., molecular mechanism of hepatitis c virus replicon variants with reduced susceptibility to a benzofuran inhibitor, hcv-796. antimicrob agents chemother, 2008. 52(9): p. 3327-38.[3]. meshram, r.j. and r.n. gacche, effective epitope identification employing phylogenetic, mutational variability, sequence entropy, and correlated mutation analysis targeting ns5b protein of hepatitis c virus: from bioinformatics to therapeutics. j mol recognit, 2015.[4]. kneteman, n.m., et al., hcv796: a selective nonstructural protein 5b polymerase inhibitor with potent anti-hepatitis c virus activity in vitro, in mice with chimeric human livers, and in humans infected with hepatitis c virus. hepatology, 2009. 49(3): p. 745-52.

Upstream product

• 1246280-91-0 phosphoric acid ((2R,3S,4R,5R)-5-(3-carbamoyl-[1,2,4]-triazol-1-yl)-3,4-dihydroxy-tetrahydrofuran-2-ylmethyl) ester 2-{[5-cyclopropyl-2-(4-fluorophenyl)-3-methylcarbamoylbenzofuran-6-yl]methanesulfonylamino}ethyl ester 
• 1246280-88-5 2-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)ethyl dihydrogen phosphate 
• 691857-56-4 6-[(2-benzyloxy-ethyl)-methanesulfonyl-amino]-5-cyclopropyl-2-(4-fluoro-phenyl)-benzofuran-3-carboxylic acid methylamide 

Downstream Products

• 1246280-89-6 4-(2-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)ethoxy)-4-oxobutanoic acid 
• 1246280-88-5 2-(N-(5-cyclopropyl-2-(4-fluorophenyl)-3-(methylcarbamoyl)benzofuran-6-yl)methylsulfonamido)ethyl dihydrogen phosphate 
• 1378427-23-6 [3-({2-[{5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-1-benzofuran-6-yl}(methylsulfonyl)amino]ethyl}oxy)propyl]boronic acid 
• 1378428-68-2 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-[(methylsulfonyl)(2-{[3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]oxy}ethyl)amino]-1-benzofuran-3-carboxamide 
• 1378427-26-9 [({2-[{5-cyclopropyl-2-(4-fluorophenyl)-3-[(methylamino)carbonyl]-1-benzofuran-6-yl}(methylsulfonyl)amino]ethyl}oxy)methyl]boronic acid 
• 1378428-67-1 5-cyclopropyl-2-(4-fluorophenyl)-N-methyl-6-{(methylsulfonyl)[2-(2-propen-1-yloxy)ethyl]amino}-1-benzofuran-3-carboxamide 

Relevant academic research and scientific papers

Design and synthesis of HCV agents with sequential triple inhibitory potentials

The union of HCV-796, a potent selective HCV NS5B polymerase inhibitor, and Ribavirin, a molecule with activities against a wide spectrum of viruses, resulted in a class of new anti-HCV agents with a sequential triple inhibitory mechanism.

COMBINATION THERAPY METHOD FOR TREATING HEPATITIS C VIRUS INFECTION AND PHARMACEUTICAL COMPOSITIONS FOR USE THEREIN

Combination therapy methods for the treatment of hepatitis C virus infection and associated diseases, by the co-administration of 5-cyclopropyl-2- (4-fluoro-phenyl-6-[(2-hydroxy-ethyl)-methanesulfonyl-amino]-benzofuran- 3-carboxylic acid methylamide or a pharmaceutically acceptable salt thereof with natural, recombinant or modified interferon, that effectively inhibit viral replication.

POLYMORPHS OF 5-CYCLOPROPYL-2-(4-FLUOROPHENYL)-6-[(2-HYDROXYETHYL)(METHYLSULFONYL) AMINO]-N-METHYL-1-BENZOFURAN-3-CARBOXAMIDE AND METHODS OF MAKING THE SAME

Substantially pure polymorphic forms of 5-cycloproρyl-2-(4- fluorophenyl)-6-[(2-hydroxyethyl)(methylsulfonyl)amino]-N-methyl-l- benzofuran-3-carboxamide are produced by recrystallization in an organic solvent.