Abstract |
Complement C1s protease inhibitors have potential utility in the treatment of diseases associated with activation of the classical complement pathway such as humorally mediated graft rejection, ischemia-reperfusion injury (IRI), vascular leak syndrome, and acute respiratory distress syndrome (ARDS). The utility of biphenylsulfonyl- thiophene-carboxamidine small-molecule C1s inhibitors are limited by their poor in vivo pharmacokinetic properties. Pegylation of a potent analog has provided compounds with good potency and good in vivo pharmacokinetic properties.
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Authors | Nalin L Subasinghe, Ehab Khalil, Jeremy M Travins, Farah Ali, Shelley K Ballentine, Heather R Hufnagel, Wenxi Pan, Kristi Leonard, Roger F Bone, Richard M Soll, Carl S Crysler, Nisha Ninan, Jennifer Kirkpatrick, Michael X Kolpak, Karen A Diloreto, Stephen H Eisennagel, Norman D Huebert, Christopher J Molloy, Bruce E Tomczuk, Michael D Gaul |
Journal | Bioorganic & medicinal chemistry letters
(Bioorg Med Chem Lett)
Vol. 22
Issue 16
Pg. 5303-7
(Aug 15 2012)
ISSN: 1464-3405 [Electronic] England |
PMID | 22795627
(Publication Type: Journal Article)
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Copyright | Copyright © 2012 Elsevier Ltd. All rights reserved. |
Chemical References |
- Amides
- Protease Inhibitors
- Thiophenes
- Polyethylene Glycols
- Complement C1s
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Topics |
- Amides
(chemistry)
- Animals
- Complement C1s
(antagonists & inhibitors, metabolism)
- Drug Design
- Half-Life
- Polyethylene Glycols
(chemistry)
- Protease Inhibitors
(chemical synthesis, chemistry, pharmacokinetics)
- Rats
- Thiophenes
(chemistry)
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