1217340-75-4Relevant academic research and scientific papers
Discovery of a Hepatitis C Virus NS5B Replicase Palm Site Allosteric Inhibitor (BMS-929075) Advanced to Phase 1 Clinical Studies
Yeung, Kap-Sun,Beno, Brett R.,Parcella, Kyle,Bender, John A.,Grant-Young, Katherine A.,Nickel, Andrew,Gunaga, Prashantha,Anjanappa, Prakash,Bora, Rajesh Onkardas,Selvakumar, Kumaravel,Rigat, Karen,Wang, Ying-Kai,Liu, Mengping,Lemm, Julie,Mosure, Kathy,Sheriff, Steven,Wan, Changhong,Witmer, Mark,Kish, Kevin,Hanumegowda, Umesh,Zhuo, Xiaoliang,Shu, Yue-Zhong,Parker, Dawn,Haskell, Roy,Ng, Alicia,Gao, Qi,Colston, Elizabeth,Raybon, Joseph,Grasela, Dennis M.,Santone, Kenneth,Gao, Min,Meanwell, Nicholas A.,Sinz, Michael,Soars, Matthew G.,Knipe, Jay O.,Roberts, Susan B.,Kadow, John F.
, p. 4369 - 4385 (2017)
The hepatitis C virus (HCV) NS5B replicase is a prime target for the development of direct-acting antiviral drugs for the treatment of chronic HCV infection. Inspired by the overlay of bound structures of three structurally distinct NS5B palm site allosteric inhibitors, the high-throughput screening hit anthranilic acid 4, the known benzofuran analogue 5, and the benzothiadiazine derivative 6, an optimization process utilizing the simple benzofuran template 7 as a starting point for a fragment growing approach was pursued. A delicate balance of molecular properties achieved via disciplined lipophilicity changes was essential to achieve both high affinity binding and a stringent targeted absorption, distribution, metabolism, and excretion profile. These efforts led to the discovery of BMS-929075 (37), which maintained ligand efficiency relative to early leads, demonstrated efficacy in a triple combination regimen in HCV replicon cells, and exhibited consistently high oral bioavailability and pharmacokinetic parameters across preclinical animal species. The human PK properties from the Phase I clinical studies of 37 were better than anticipated and suggest promising potential for QD administration.
BENZOFURAN DERIVATIVES FOR THE TREATMENT OF HEPATITIS C
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, (2013/10/21)
The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and may be useful in treating those infected with HCV.
BENZOFURANE DERIVATIVES FOR THE TREATMENT OF HEPATITITS C
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, (2012/06/30)
The disclosure provides compounds of formula I, including their salts, as well as compositions and methods of using the compounds. The compounds have activity against hepatitis C virus (HCV) and maybe useful in treating those infected with HCV.
