1228969-01-4

Upstream product

• 106-37-6 1.4-dibromobenzene 
• 1208009-37-3 (S)-2-(6-(4,4,5,5-tetramethyl-1,3,2-dioxapentane-2-yl)-1H-benzo[d]imidazole -2-yl)pyrrolidine-1-carboxylic acid tert-butyl ester 
• 1208007-67-3 1,1-dimethylethyl (2S)-2-(5-bromo-1H-benzimidazol-2-yl)-1-pyrrolidinecarboxylate 
• 1228553-72-7 (2S)-1-tert-butoxycarbonyl-2-(2-amino-4-bromophenylaminoacyl)pyrrolidine 
• 1575-37-7 4-Bromo-benzene-1,2-diamine 
• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 589-87-7 1,4-bromoiodobenzene 
• 1208009-37-3 (S)-tert-butyl 2-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate 
• 24424-99-5 di-tert-butyl dicarbonate 
• 147-85-3 L-proline 
• 59378-82-4 N-(tert-butoxycarbonyl)pyrrolidine-2-carboxaldehyde 
• 1208007-67-3 (S)-tert-butyl 2-(6-bromo-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate 

Downstream Products

• 1228969-02-5 C₃₈H₄₅N₇O₅ 
• 1228968-06-6 (1-{2-[6-(4-{2-[1-(2-methoxycarbonylamino-3-methylbutyryl)pyrrolidin-2-yl]-3Himidazol-4-ylethynyl}phenyl)-1H-benzoimidazol-2-yl]pyrrolidine-1-carbonyl}-2-methylpropyl)carbamic acid methyl ester 
• 1256387-59-3 (S)-2-(acetoxyamino)-1-((S)-2-(6-(4-bromophenyl)-1H-benzo[d]imidazol-2-yl)pyrrolidin-1-yl)-3-methylbutan-1-one 
• 1256385-57-5 (S)-tert-butyl 2-(6-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1Hbenzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate 
• 1241378-08-4 C₄₀H₄₆N₆O₄ 
• 1256385-57-5 (S)-tert-butyl 2-(5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1H-benzo[d]imidazol-2-yl)pyrrolidine-1-carboxylate 
• 1275033-97-0 C₃₉H₄₇N₅O₅ 
• 1275033-98-1 C₃₉H₄₇N₅O₅ 
• 1352212-17-9 methyl {(2S)-1-[(2S)-2-{4-[2-(4-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl]-1H-benzimidazol-5-yl}phenyl)pyrimidin-5-yl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate 
• 1352212-18-0 methyl {(2S)-1-[(2S)-2-{4-[5-(4-{2-[(2S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}pyrrolidin-2-yl]-1H-benzimidazol-5-yl}phenyl)pyrimidin-2-yl]-1H-imidazol-2-yl}pyrrolidin-1-yl]-3-methyl-1-oxobutan-2-yl}carbamate 
• 1352212-54-4 tert-butyl (2S)-2-{5-[4-(5-bromopyrimidin-2-yl)phenyl]-1H-benzimidazol-2-yl}pyrrolidine-1-carboxylate 
• 1352212-55-5 tert-butyl (2S)-2-(5-[2-(4-{2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]-1H-benzimidazol-5-yl}phenyl)pyrimidin-5-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)pyrrolidine-1-carboxylate 
• 1352212-58-8 tert-butyl (2S)-2-(5-[5-(4-{2-[(2S)-1-(tert-butoxycarbonyl)pyrrolidin-2-yl]-1H-benzimidazol-5-yl}phenyl)pyrimidin-2-yl]-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazol-2-yl)pyrrolidine-1-carboxylate 

Relevant academic research and scientific papers

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.

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.

Discovery of ledipasvir (GS-5885): A potent, once-daily oral NS5A inhibitor for the treatment of hepatitis C virus infection

A new class of highly potent NS5A inhibitors with an unsymmetric benzimidazole-difluorofluorene-imidazole core and distal [2.2.1]azabicyclic ring system was discovered. Optimization of antiviral potency and pharmacokinetics led to the identification of 39 (ledipasvir, GS-5885). Compound 39 (GT1a replicon EC50 = 31 pM) has an extended plasma half-life of 37-45 h in healthy volunteers and produces a rapid >3 log viral load reduction in monotherapy at oral doses of 3 mg or greater with once-daily dosing in genotype 1a HCV-infected patients. 39 has been shown to be safe and efficacious, with SVR12 rates up to 100% when used in combination with direct-acting antivirals having complementary mechanisms.

HEPATITIS C VIRUS INHIBITORS

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. The present invention relates to novel antiviral compounds represented herein above, pharmaceutical compositions comprising such compounds, and methods for the treatment or prophylaxis of viral (particularly HCV) infection in a subject in need of such therapy with said compounds.

INHIBITORS OF HCV NS5A

Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.

LINKED DIBENZIMIDAZOLE DERIVATIVES

The present invention discloses linked dibenzimidazole derivatives, 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.

HEPATITIS C VIRUS INHIBITORS

The present invention discloses compounds 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.

INHIBITORS OF HCV NS5A

Provided herein are compounds, pharmaceutical compositions and combination therapies for inhibition of hepatitis C.