A novel series of arylsulfonylthiophene-2-carboxamidine inhibitors of the complement component C1s

被引：17

作者：

Subasinghe, NL ^{[1
]}

Travins, JM ^{[1
]}

Ali, F ^{[1
]}

Huang, H ^{[1
]}

Ballentine, SK ^{[1
]}

Marugán, JJ ^{[1
]}

Khalil, E ^{[1
]}

Hufnagel, HR ^{[1
]}

Bone, RF ^{[1
]}

DesJarlais, RL ^{[1
]}

Crysler, CS ^{[1
]}

Ninan, N ^{[1
]}

Cummings, MD ^{[1
]}

Molloy, CJ ^{[1
]}

Tomczuk, BE ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev LLC, Exton, PA 19341 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 08期

关键词：

classical pathway; complement; C1s; complement inhibitor; C1s inhibitor; classical pathway inhibitor;

D O I：

10.1016/j.bmcl.2006.01.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Inhibiting the classical pathway of complement activation by attenuating the proteolytic activity of the serine protease C1s is a potential strategy for the therapeutic intervention in disease states such as hereditary angioedema, ischemia-reperfusion injury, and acute transplant rejection. A series of arylsulfonylthiophene-2-carboximidine inhibitors of C1s were synthesized and evaluated for C1s inhibitory activity. The most potent compound had a K-i of 10 nM and >1000-fold selectivity over uPA, tPA, FXa, thrombin, and plasmin. (C) 2006 Elsevier Ltd. All rights reserved.

引用

页码：2200 / 2204

页数：5

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