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Drug profiles: generic names A–Z
Published in Jerome Z. Litt, Neil H. Shear, Litt's Drug Eruption & Reaction Manual, 2017
Clinically important, potentially hazardous interactions with: boceprevir, carbamazepine, clarithromycin, cobicistat, conivaptan, danoprevir, dasabuvir/ombitasvir/paritaprevir/ritonavir, diltiazem, elvitegravir, enzalutamide, grapefruit juice, idelalisib, indinavir, itraconazole, ketoconazole, lopinavir, mitotane, nefazodone, nelfinavir, phenytoin, posaconazole, rifampin, ritonavir, saquinavir, St John’s wort, strong CYP3A inhibitors and inducers, tipranavir, troleandomycin, voriconazole
Mechanisms of Hepatitis C Virus Clearance by Interferon and Ribavirin Combination
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Srikanta Dash, Partha K. Chandra, Kurt Ramazan, Robert F. Garry, Luis A. Balart
NS3 protease is a bifunctional enzyme that contains serine protease in the N-terminal 180 amino acid residues. The search for small molecule inhibitors led to the identification of the first-generation protease inhibitors: telaprevir and boceprevir. Additional second generation NS3/4A protease inhibitors simeprevir (TMC435), faldaprevir, and danoprevir are in the clinical stage of development. Preliminary studies using them in naïve patients suggested that each of these second-generation protease inhibitors produces a better antiviral response than the first-generation protease inhibitors.
Benzoxaborole compounds for therapeutic uses: a patent review (2010- 2018)
Published in Expert Opinion on Therapeutic Patents, 2018
Alessio Nocentini, Claudiu T. Supuran, Jean-Yves Winum
Between 2010 and 2011, researchers from Anacor Pharmaceuticals Inc. and GlaxoSmithKline reported three studies on the design and synthesis of new HCV NS3/4A protease inhibitors, having a benzoxaborole moiety. The first study was dealing with synthesis of five acyl sulfamoyl benzoxaborole derivatives of the two HCV NS3 protease inhibitors, Danoprevir and Vaniprevir [30]. The main objective of the authors was to optimize the interaction with the P1 carboxylic acid region of the protease. All five compounds exhibited equipotent nanomolar inhibitory activity against HCV NS3/4A protease as Danoprevir. Nevertheless, they were less potent than Danoprevir, on HCV replicon assays. First in vivo pharmacokinetic study on two compounds of this series, 21 and 22, showed poor oral bioavailability caused by limited absorption compared to Danoprevir. In the second study reported in 2010 [85], the authors considered targeting the P4 region of the protease peptide framework with a benzoxaborole moiety. This series demonstrated nanomolar inhibitory potency against HCV NS3/4A protease. Pharmacokinetic properties evaluation of selected compounds 23, 24, and 25 (Figure 15) revealed the poor absorption and bioavailability of these derivatives, even if water solubility was improved. This study was then extended in 2011 by a new series of P4-benzoxaborole-based NS3 protease inhibitors [86]. These compounds exhibited nanomolar inhibitory activities in enzymatic assays and nanomolar potencies in cell-based replicon assays. As observed in the previous studies from 2010, pharmacokinetic studies utilizing a rat model revealed a low oral availability of this new inhibitor series, but encouraging results were pointed out by the author for compound 26 (Figure 16) that showed the best absorption profile in vitro and in vivo.