Author: Beno, Brett R. ; Yeung, Kap-Sun ; Ng, Alicia ; Soars, Matthew G. ; Wang, Ying-Kai ; Bender, John A. ; Gao, Min ; Santone, Kenneth ; Shu, Yue-Zhong ; Sinz, Michael ; Mosure, Kathy ; Bora, Rajesh Onkardas ; Kadow, John F. ; Wan, Changhong ; Roberts, Susan B. ; Witmer, Mark ; Liu, Mengping ; Meanwell, Nicholas A. ; Grant-Young, Katherine A. ; Kish, Kevin ; Hanumegowda, Umesh ; Haskell, Roy ; Anjanappa, Prakash ; Colston, Elizabeth ; Nickel, Andrew ; Grasela, Dennis M. ; Parcella, Kyle ; Sheriff, Steven ; Gao, Qi ; Zhuo, Xiaoliang ; Selvakumar, Kumaravel ; Parker, Dawn ; Knipe, Jay O. ; Rigat, Karen ; Raybon, Joseph ; Gunaga, Prashantha ; Lemm, Julie

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.

01 Jan 2007·Expert Opinion on Investigational DrugsQ2 · MEDICINE

Discontinued drugs in 2005: anti-infectives

Q2 · MEDICINE

Review

Author: Georgopapadakou, Nafsika

This perspective is the fifth in a series discussing drugs dropped from development in 2005, of which 11 were being developed for infectious diseases. Of these, eight were antivirals and were dropped in Phase II or III: Medivir's alovudine, Ono Pharmaceuticals' aplaviroc hydrochloride and Excite's immunotherapeutic Xcellerate for HIV; Boehringer Ingelheim's ciluprevir, ViroPharma's HCV-086, Isis Pharmaceuticals' antisense oligonucleotide ISIS-14803, Japan Tobacco's JTK-003 and Rigel's R803 for hepatitis C virus. The remaining discontinued anti-infective drugs were an antibacterial vaccine (Vical's anthrax vaccine), an antiseptic (YM Bioscience's Dermofural) and an antifungal formulation (MacroChem's topical econazole). The drugs are grouped by compound class and reasons for their failure are discussed in this article.

100 Deals associated with HCV-086

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05884

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Hepatitis C	Phase 1	United States	Wyeth Pharmaceuticals LLC	24 Feb 2004
Hepatitis C	Phase 1	United States	Shire ViroPharma, Inc.	24 Feb 2004

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis