| Autor: |
Frank, Narjes, Benedetta, Crescenzi, Marco, Ferrara, Jörg, Habermann, Stefania, Colarusso, Maria del Rosario Rico, Ferreira, Ian, Stansfield, Angela Claire, Mackay, Immacolata, Conte, Caterina, Ercolani, Simone, Zaramella, Maria-Cecilia, Palumbi, Philip, Meuleman, Geert, Leroux-Roels, Claudio, Giuliano, Fabrizio, Fiore, Stefania, Di Marco, Paola, Baiocco, Uwe, Koch, Giovanni, Migliaccio, Sergio, Altamura, Ralph, Laufer, Raffaele, De Francesco, Michael, Rowley |
| Jazyk: |
angličtina |
| Rok vydání: |
2011 |
| Předmět: |
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| Popis: |
Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral genome and has been a prime target for drug discovery efforts. Here, we report on the further development of tetracyclic indole inhibitors, binding to an allosteric site on the thumb domain. Structure-activity relationship (SAR) studies around an indolo-benzoxazocine scaffold led to the identification of compound 33 (MK-3281), an inhibitor with good potency in the HCV subgenomic replication assay and attractive molecular properties suitable for a clinical candidate. The compound caused a consistent decrease in viremia in vivo using the chimeric mouse model of HCV infection. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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