Results 191 to 200 of about 9,765 (234)

Orally bioavailable HCV NS5A inhibitors of unsymmetrical structural class

Bioorganic & Medicinal Chemistry Letters, 2020
A novel unsymmetrical structural class of orally bioavailable hepatitis C virus (HCV) nonstructural 5A protein (NS5A) inhibitors has been generated by improving both the solubility and membrane permeability of the lead compound found in our previous work.
Hiroshi, Nakamura, Shingo, Fujioka, Takashi, Terui, Satoshi, Okuda, Kentaro, Kondo, Yoshinori, Tamatani, Yusuke, Akagi, Yasumasa, Komoda, Wataru, Kinoshita, Soichiro, Ito, Kimiya, Maeda, Yutaka, Ukaji, Takashi, Inaba   +12 more
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HCV NS5A Inhibitors in Development

Clinics in Liver Disease, 2013
NS5A protein plays a key role in hepatitis C virus (HCV) replication. Daclatasvir (DCV, BMS-790052) is a first-in-class inhibitor of the HCV NS5A replication complex with potent antiviral activity but a low barrier to resistance. DCV as triple therapy in combination with pegylated interferon and ribavirin resulted in a high rate of early virologic ...
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In Silico Approaches to the Design of NS5A Inhibitors

Current Topics in Medicinal Chemistry, 2016
In recent years, nonstructural protein 5A (NS5A) has rapidly emerged as a promising therapeutic target for Hepatitis C (HCV) virus therapy. It is involved in both viral RNA replication and virus assembly and NS5A plays a critical role in the regulation of HCV life cycle. NS5A replication complex inhibitors (NS5A RCIs) have demonstrated strong antiviral
Yan A, Ivanenkov, Mark S, Veselov, Vladimir A, Aladinskiy, Artem G, Shakhbazyan, Sofya M, Yartseva, Alexander G, Majouga, Anastasia V, Aladinskaya, Anton S, Vantskul, Sergey V, Leonov, Alexandre V, Ivachtchenko, Victor E, Koteliansky   +10 more
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Prevalence of Natural Polymorphisms at the HCV Ns5A Gene Associated with Resistance to Daclatasvir, An Ns5A Inhibitor

Antiviral Therapy, 2012
Background Daclatasvir (BMS-790052) is an investigational molecule that inhibits the HCV NS5A protein and shows potent antiviral activity apparently across all HCV genotypes. Selection of drug resistance mutations has been reported only for HCV genotype 1, and no information exists for other HCV variants and/or in HIV–HCV-coinfected individuals ...
Plaza, Zulema, Soriano, Vincent, Vispo, Eugenia, del Mar Gonzalez, Maria, Barreiro, Pablo, Seclén, Eduardo, Poveda, Eva   +6 more
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Potent bisimidazole-based HCV NS5A inhibitors bearing annulated tricyclic motifs

Bioorganic & Medicinal Chemistry Letters, 2014
This Letter describes the synthesis and biological evaluation of a number of functionalized bisimidazoles bearing annulated tricyclic motifs as potent inhibitors of HCV NS5A protein. Compound 4 h, which contains a substituted tricyclic 6-6-6 xanthene, demonstrated broad genotypic spectrum, compelling potency, and good oral bioavailability with dose ...
Min, Zhong, Eric, Peng, Ningwu, Huang, Qi, Huang, Anja, Huq, Meiyen, Lau, Richard, Colonno, Leping, Li   +7 more
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Alkyl substituted aminal derivatives of HCV NS5A inhibitor MK-8742

Bioorganic & Medicinal Chemistry Letters, 2016
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.
Wensheng Yu, Craig A. Coburn, Anilkumar G. Nair, Michael Wong, Ling Tong, Michael P. Dwyer, Bin Hu, Bin Zhong, Jinglai Hao, De-Yi Yang, Oleg Selyutin, Yueheng Jiang, Stuart B. Rosenblum, Seong Heon Kim, Brian J. Lavey, Guowei Zhou, Razia Rizvi, Bandarpalle B. Shankar, Qingbei Zeng, Lei Chen, Sony Agrawal, Donna Carr, Laura Rokosz, Rong Liu, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Fred Lahser, Ernest Asante-Appiah, Amin Nomeir, Joseph A. Kozlowski   +30 more
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Synthesis and evaluation of NS5A inhibitors containing diverse heteroaromatic cores

Bioorganic & Medicinal Chemistry Letters, 2015
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 ...
James A, Henderson, Darius, Bilimoria, Monica, Bubenik, Caroline, Cadilhac, Kevin M, Cottrell, Francois, Denis, Evelyne, Dietrich, Nigel, Ewing, Guy, Falardeau, Simon, Giroux, Lucille, L'Heureux, Bingcan, Liu, Nagraj, Mani, Mark, Morris, Olivier, Nicolas, Oswy Z, Pereira, Carl, Poisson, T Jagadeeswar, Reddy, Subajini, Selliah, Rebecca S, Shawgo, Louis, Vaillancourt, Jian, Wang, Jinwang, Xu, Nathalie, Chauret, Francoise, Berlioz-Seux, Laval C, Chan, Sanjoy K, Das, Anne-Laure, Grillot, Youssef L, Bennani, John P, Maxwell   +29 more
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Ser38‐His93‐Asn91 triad confers resistance of JFH1 HCV NS5A‐Y93H variant to NS5A inhibitors

The FEBS Journal
HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct‐acting antivirals (DAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38‐His93‐Asn91 triad to dissect the mechanism. Using
Wei‐Ping Lee, Keng‐Chang Tsai, Shi‐Xian Liao, Yi‐Hsiang Huang, Ming‐Chih Hou, Keng‐Hsin Lan   +5 more
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Substituted tetracyclic indole core derivatives of HCV NS5A inhibitor MK-8742

Bioorganic & Medicinal Chemistry Letters, 2016
As part of an ongoing effort in NS5A inhibition at Merck we now describe our efforts for introducing substitution around the tetracyclic indole core of MK-8742. Fluoro substitution on the core combined with the fluoro substitutions on the proline ring improved the potency against GT1a Y93H significantly.
Wensheng Yu, Guowei Zhou, Craig A. Coburn, Qingbei Zeng, Ling Tong, Michael P. Dwyer, Bin Hu, Bin Zhong, Jinglai Hao, Tao Ji, Shuai Zan, Lei Chen, Robert Mazzola, Jae-Hun Kim, Deyou Sha, Oleg Selyutin, Stuart B. Rosenblum, Brian Lavey, Anilkumar G. Nair, Seong Heon Kim, Kerry M. Keertikar, Laura Rokosz, Sony Agrawal, Rong Liu, Ellen Xia, Ying Zhai, Stephanie Curry, Patricia McMonagle, Paul Ingravallo, Ernest Asante-Appiah, Shiying Chen, Joseph A. Kozlowski   +31 more
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Discovery of Novel Highly Potent Hepatitis C Virus NS5A Inhibitor (AV4025)

Journal of Medicinal Chemistry, 2014
A series of next in class small-molecule hepatitis C virus (HCV) NS5A inhibitors with picomolar potency containing 2-pyrrolidin-2-yl-5-{4-[4-(2-pyrrolidin-2-yl-1H-imidazol-5-yl)buta-1,3-diynyl]phenyl}-1H-imidazole cores was designed based on the SAR studies available for the reported NS5A inhibitors.
Alexandre V, Ivachtchenko, Oleg D, Mitkin, Pavel M, Yamanushkin, Irina V, Kuznetsova, Elena A, Bulanova, Natalia A, Shevkun, Angela G, Koryakova, Ruben N, Karapetian, Vadim V, Bichko, Andrey S, Trifelenkov, Dmitry V, Kravchenko, Natalia V, Vostokova, Mark S, Veselov, Nina V, Chufarova, Yan A, Ivanenkov   +14 more
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