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The book details the synthesis of molecules designed to inhibit the hepatitis C virus (HCV) NS3 serine protease and the human aspartic protease BACE-1. It explores the relationships between potential inhibitors and the targeted enzymes while discussing the class of enzymes known as proteases. The book also discusses why such enzymes can be regarded as suitable targets for developing drugs to combat diseases. It presents the results of the design and synthesis of linear and macrocyclic NS3 protease inhibitors containing a novel trisubstituted cyclopentane moiety as an N-acyl-(4 bioisostere. The book is intended for researchers and students in the field of medicinal chemistry and drug design.
Aspartic Proteinases. --- Hepatitis C Virus. --- Enzyme Inhibitors.
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Hepatitis C virus. --- Hepatitis, Viral. --- Hepatitis viruses.
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There is great potential to improve health outcomes for Veterans and other patients with chronic genotype 1 (GT1) Hepatitis C (HCV) infections through the use of newly-available triple combination therapies that include directly acting antivirals (DAA) along with recently developed patient genotyping (IL-28B) which is predictive of HCV treatment response. Chronic GT1 HCV infections have been historically difficult to treat, with low cure rates on standard two drug therapy (Pegylated Interferon + Ribavirin), high rates of side-effects and treatment discontinuation, and low rates of uptake. Recently, FDA approved two DAAs (boceprevir and telaprevir). Used in combination with standard two drug therapy as triple therapy, these DAAs show higher rates of sustained viral response, though they are also more costly and have more severe side-effect profiles. IL-28B genotyping can help to identify patients least likely to respond to standard therapy and hence who stand to benefit the most from triple therapy and for whom, therefore, the increased risks of side-effects may be most justified.
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Hepatitis C --- Hepatitis C virus --- Prevention. --- Transmission
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Hepatitis C virus --- Hepatitis C virus. --- Blood - Transfusion - Complications. --- Hepatitis C - Prevention.
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