Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 22, Issue 15, Pages 4955-4961Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.06.038
Keywords
Hepatitis C virus; Entry inhibitors; Bioisostere; Oral bioavailability; Scavenger receptor B-1
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The manuscript reports an identification of a highly potent, orally bioavailable hepatitis C virus entry inhibitor through optimization of a previously reported class of molecules (1) that were not stable in the rat plasma. Compound 39 (ITX 4520) exhibited an excellent PK profile in both rats and dogs with good oral exposure, half-life and oral bioavailability. The compound is also well-tolerated in the preliminary in vivo toxicity studies and has been selected as a pre-clinical candidate for our HCV clinical pipeline. (c) 2012 Elsevier Ltd. All rights reserved.
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