Discovery of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid diamides that increase CFTR mediated chloride transport

被引：22
作者：
Hirth, BH [1 ]
Qiao, SA [1 ]
Cuff, LM [1 ]
Cochran, BM [1 ]
Pregel, MJ [1 ]
Gregory, JS [1 ]
Sneddon, CF [1 ]
Kane, JL [1 ]
机构：
[1] Genzyme Corp, Genzyme Drug Discovery & Dev, Cambridge, MA 02139 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 08期
关键词：
CFTR; cystic fibrosis;
D O I：
10.1016/j.bmcl.2005.02.041
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid diamides that increase chloride transport in cells expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein has been identified from our compound library. Analoging efforts and the resulting structure-activity relationships uncovered are detailed. Compound potency was improved over 30-fold from the original lead, yielding several analogs with EC50 values below 10 nM in our cellular chloride transport assay. (c) 2005 Elsevier Ltd. All rights reserved.
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收藏
页码：2087 / 2091
页数：5
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