iTherX Pharmaceuticals, Inc., San Diego, CA 92191-0530, USA.
Bioorg Med Chem Lett. 2012 Aug 1;22(15):4955-61. doi: 10.1016/j.bmcl.2012.06.038. Epub 2012 Jun 19.
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.
本文报道了通过优化先前报道的一类在大鼠血浆中不稳定的分子（1），鉴定出一种高效、口服生物利用度的丙型肝炎病毒进入抑制剂。化合物 39（ITX 4520）在大鼠和犬中均表现出优异的 PK 特征，具有良好的口服暴露量、半衰期和口服生物利用度。该化合物在初步的体内毒性研究中也具有良好的耐受性，并已被选为我们丙型肝炎病毒临床研发管线的临床前候选药物。
