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Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742.
Yu, Wensheng; Coburn, Craig A; Nair, Anilkumar G; Wong, Michael; Tong, Ling; Dwyer, Michael P; Hu, Bin; Zhong, Bin; Hao, Jinglai; Yang, De-Yi; Selyutin, Oleg; Jiang, Yueheng; Rosenblum, Stuart B; Kim, Seong Heon; Lavey, Brian J; Zhou, Guowei; Rizvi, Razia; Shankar, Bandarpalle B; Zeng, Qingbei; Chen, Lei; Agrawal, Sony; Carr, Donna; Rokosz, Laura; Liu, Rong; Curry, Stephanie; McMonagle, Patricia; Ingravallo, Paul; Lahser, Fred; Asante-Appiah, Ernest; Nomeir, Amin; Kozlowski, Joseph A.
Afiliação
  • Yu W; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA. Electronic address: wensheng.yu@merck.com.
  • Coburn CA; Department of Medicinal Chemistry, Merck Research Laboratories, 770 Sumneytown Pike, West Point, PA 19486, USA.
  • Nair AG; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Wong M; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Tong L; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Dwyer MP; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Hu B; WuXi AppTec, 288 Fute Zhong Road, Shanghai 200131, China.
  • Zhong B; WuXi AppTec, 288 Fute Zhong Road, Shanghai 200131, China.
  • Hao J; WuXi AppTec, 288 Fute Zhong Road, Shanghai 200131, China.
  • Yang DY; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Selyutin O; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Jiang Y; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Rosenblum SB; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Kim SH; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Lavey BJ; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Zhou G; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Rizvi R; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Shankar BB; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Zeng Q; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Chen L; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
  • Agrawal S; Department of In Vitro Pharmacology, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Carr D; Department of In Vitro Pharmacology, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Rokosz L; Department of In Vitro Pharmacology, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Liu R; Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Curry S; Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • McMonagle P; Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Ingravallo P; Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Lahser F; Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Asante-Appiah E; Department of Infectious Diseases, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Nomeir A; Department of PPDM, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
  • Kozlowski JA; Department of Medicinal Chemistry, Merck Research Laboratories, 126 E. Lincoln Avenue, Rahway, NJ 07065, USA.
Bioorg Med Chem Lett ; 26(15): 3800-5, 2016 08 01.
Article em En | MEDLINE | ID: mdl-27282742
ABSTRACT
HCV NS5A inhibitors have demonstrated impressive in vitro potency profiles in HCV replicon assays and robust HCV RNA titer reduction in the clinic making them attractive components for inclusion in an all oral fixed dose combination regimen for the treatment of HCV infection. Herein we describe our continued research efforts around the alkyl "Z group" modification of the tetracyclic indole-based NS5A inhibitor MK-8742, which led to the discovery of a series of potent NS5A inhibitors. Compounds 10 and 19 are of particular interests since they are as potent as our previous leads and have much improved rat pharmacokinetic profiles.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Benzofuranos / Proteínas não Estruturais Virais / Hepacivirus / Imidazóis Limite: Animals Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Antivirais / Benzofuranos / Proteínas não Estruturais Virais / Hepacivirus / Imidazóis Limite: Animals Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article