Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa

Stephen Hanessian; Andreas Larsson; Tomas Fex; Wolfgang Knecht; Niklas Blomberg

doi:10.1016/j.bmcl.2010.09.141

Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa

Bioorg Med Chem Lett. 2010 Dec 1;20(23):6925-8. doi: 10.1016/j.bmcl.2010.09.141. Epub 2010 Oct 8.

Authors

Stephen Hanessian¹, Andreas Larsson, Tomas Fex, Wolfgang Knecht, Niklas Blomberg

Affiliation

¹ Department of Chemistry, Université de Montréal, Montréal, QC, Canada. stephen.hanessian@umontreal.ca

PMID: 21035339
DOI: 10.1016/j.bmcl.2010.09.141

Abstract

The synthesis of a series of novel macrocyclic compounds designed to target blood coagulation Factor XIa is described. The compounds were evaluated for their inhibition of a small set of serine proteases. Several compounds displayed modest activity and good selectivity for Factor XIa. Within the series, a promising lead structure for developing novel macrocyclic inhibitors of thrombin was identified.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anticoagulants / chemical synthesis*
Anticoagulants / pharmacology
Blood Coagulation / drug effects
Drug Design
Factor XIa / antagonists & inhibitors*
Indoles / chemistry
Indoles / pharmacology*
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology
Structure-Activity Relationship

Substances

Anticoagulants
Indoles
Serine Proteinase Inhibitors
Factor XIa