Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 22, Issue 16, Pages 5303-5307Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2012.06.030
Keywords
Complement inhibitors; C1s inhibitors; Pegylation; Pegylated small molecule; Polyethylene glycol-modified; Pharmacokinetics; Polyethylene glycol-modified small molecule; Pegylated molecule pharmacokinetics; Pegylated molecule PK
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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. (C) 2012 Elsevier Ltd. All rights reserved.
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