Trypsin inhibitors for the treatment of pancreatitis

  • Bioorg Med Chem Lett. 2016 Sep 1;26(17):4340-4. doi: 10.1016/j.bmcl.2016.07.029.
Trixi Brandl  1 ,  Oliver Simic  2 ,  Philip R Skaanderup  2 ,  Kenji Namoto  2 ,  Frederic Berst  2 ,  Claus Ehrhardt  2 ,  Nikolaus Schiering  2 ,  Irene Mueller  2 ,  Julian Woelcke  3
Affiliations
  • 1. Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland. Electronic address: [email protected].
  • 2. Novartis Pharma AG, Novartis Institutes for BioMedical Research, Novartis Campus, CH-4002 Basel, Switzerland.
  • 3. Novartis Pharma AG, Cardio Metabolic Development Franchise, Novartis Campus, CH-4002 Basel, Switzerland.
PMID: 27476144 DOI: 10.1016/j.bmcl.2016.07.029
Abstract

Proline-based trypsin inhibitors occupying the S1-S2-S1' region were identified by an HTS screening campaign. It was discovered that truncation of the P1' moiety and appropriate extension into the S4 region led to highly potent trypsin inhibitors with excellent selectivity against related serine proteases and a favorable hERG profile.

Keywords
Pancreatitis; Trypsin inhibitor; X-ray crystal structure; hERG inhibition.
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