1242094-26-3Relevant 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
Abdallah, Mennatallah,Hamed, Mostafa M.,Frakolaki, Efseveia,Katsamakas, Sotirios,Vassilaki, Niki,Bartenschlager, Ralf,Zoidis, Grigoris,Hirsch, Anna K.H.,Abdel-Halim, Mohammad,Abadi, Ashraf H.
, (2021/12/27)
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
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, (2010/09/17)
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.
