Discovery of ITX 4520: A highly potent orally bioavailable hepatitis C virus entry inhibitor

被引：19
|
作者：
Mittapalli, Gopi Kumar [1 ]
Zhao, Fang [1 ]
Jackson, Andrew [1 ]
Gao, Hongfeng [1 ]
Lee, Haekyung [1 ]
Chow, Stephine [1 ]
Kaur, Maninder Pal [1 ]
Natalie Nguyen [1 ]
Zamboni, Robert [1 ]
McKelvy, Jeffrey [1 ]
Wong-Staal, Flossie [1 ]
Macdonald, James E. [1 ]
机构：
[1] iTherX Pharmaceut Inc, San Diego, CA 92191 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 15期
关键词：
Hepatitis C virus; Entry inhibitors; Bioisostere; Oral bioavailability; Scavenger receptor B-1; HCV ENTRY; INFECTION; RECEPTOR; CULTURE; DRUGS;
D O I：
10.1016/j.bmcl.2012.06.038
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
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.
引用
收藏
页码：4955 / 4961
页数：7
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