1219630-39-3

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 6052-15-9 4,4'-(ethyne-1,2-diyl)dianiline 

Downstream Products

• 1219630-12-2 (2S,2’S)-N,N’-(1,2-ethynediyldi-4,1-phenylene)bis(1-(phenylacetyl)-2-pyrrolidinecarboxamide) 
• 1219630-42-8 C₄₂H₄₂N₄O₆ 
• 1219630-41-7 (2S,2’S)-N,N’-(1,2-ethynediyldi-4,1-phenylene)bis(1-((2S)-2-hydroxy-2-phenylpropanoyl)-2-pyrrolidinecarboxamide) 
• 1219631-66-9 C₄₀H₄₀N₆O₄ 
• 1219631-63-6 C₄₀H₄₀N₆O₄ 
• 1219630-52-0 C₄₈H₅₂N₆O₄ 
• 1219630-54-2 C₄₈H₅₂N₆O₆ 
• 1219631-65-8 di-tert-butyl (1,2-ethynediylbis(4,1-phenylenecarbamoyl(2S)-2,1-pyrrolidinediyl((1R)-2-oxo-1-phenyl-2,1-ethanediyl)))biscarbamate 
• 1219631-62-5 di-tert-butyl (1,2-ethynediylbis(4,1-phenylenecarbamoyl(2S)-2,1-pyrrolidinediyl((1S)-2-oxo-1-phenyl-2,1-ethanediyl)))biscarbamate 
• 1219631-72-7 C₅₂H₆₀N₆O₈ 
• 1219631-75-0 C₅₂H₆₀N₆O₈ 
• 1219631-73-8 C₄₂H₄₄N₆O₄ 
• 1219631-76-1 C₄₂H₄₄N₆O₄ 

Relevant academic research and scientific papers

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.

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.

HCV NS5A replication complex inhibitors. Part 4.1 optimization for genotype 1a replicon inhibitory activity

A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging f

HCV NS5A replication complex inhibitors. Part 3

In a recent disclosure,1 we described the discovery of dimeric, prolinamide-based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon. That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype, and herein is described the SAR uncovered from a complementary effort that focused on the central core region. From this effort, the contribution of the core region to the overall topology of the pharmacophore, primarily vector orientation and planarity, was determined, with a set of analogs exhibiting 50 in a genotype 1b replicon assay.

HCV NS5A replication complex inhibitors. Part 5: Discovery of potent and pan-genotypic glycinamide cap derivatives

The isoquinolinamide series of HCV NS5A inhibitors exemplified by compounds 2b and 2c provided the first dual genotype-1a/1b (GT-1a/1b) inhibitor class that demonstrated a significant improvement in potency toward GT-1a replicons compared to that of the initial program lead, stilbene 2a. Structure-activity relationship (SAR) studies that uncovered an alternate phenylglycine-based cap series that exhibit further improvements in virology profile, along with some insights into the pharmacophoric elements associated with the GT-1a potency, are described.