Synthesis and evaluation of NS5A inhibitors containing diverse heteroaromatic cores
| Autor: | Anne-Laure Grillot, Nigel Ewing, Youssef L. Bennani, Simon Giroux, Nathalie Chauret, Caroline Cadilhac, Kevin M. Cottrell, Olivier Nicolas, T. Jagadeeswar Reddy, Evelyne Dietrich, Lucille L’Heureux, Francois Denis, Oswy Z. Pereira, Rebecca S. Shawgo, Jinwang Xu, Nagraj Mani, Francoise Berlioz-Seux, Jian Wang, Sanjoy Kumar Das, John Maxwell, Bingcan Liu, James A. Henderson, Louis Vaillancourt, Subajini Selliah, Guy Falardeau, Laval C. Chan, Morris Mark A, Carl Poisson, Darius Bilimoria, Monica Bubenik |
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| Rok vydání: | 2014 |
| Předmět: |
Ledipasvir
Daclatasvir viruses Clinical Biochemistry Pharmaceutical Science Hepacivirus Viral Nonstructural Proteins Biochemistry Antiviral Agents chemistry.chemical_compound Structure-Activity Relationship Amide Drug Discovery medicine Structure–activity relationship NS5A Molecular Biology Organic Chemistry virus diseases biochemical phenomena metabolism and nutrition Combinatorial chemistry digestive system diseases Ombitasvir chemistry Molecular Medicine Pharmacophore medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 25(4) |
| ISSN: | 1464-3405 |
| Popis: | Inhibitors of the HCV NS5A nonstructural protein are showing promising clinical potential in the treatment of hepatitis C when used in combination with other direct-acting antiviral agents. Current NS5A clinical candidates such as daclatasvir, ledipasvir, and ombitasvir share a common pharmacophore that features a pair of (S)-methoxycarbonylvaline capped pyrrolidines linked to various cores by amides, imidazoles and/or benzimidazoles. In this Letter, we describe the evaluation of NS5A inhibitors which contain alternative heteroaromatic replacements for these amide mimetics. The SAR knowledge gleaned in the optimization of scaffolds containing benzoxazoles was parlayed toward the identification of potent NS5A inhibitors containing other heteroaromatic replacements such as indoles and imidazopyridines. |
| Databáze: | OpenAIRE |
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