BIOMAT Database Logo BIOMAT Database Logo

Design and synthesis of macrocyclic indoles targeting blood coagulation cascade Factor XIa. 2010

Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Department of Chemistry, Université de Montréal, Montréal, QC, Canada. stephen.hanessian@umontreal.ca

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.

UI MeSH Term Description Entries
D007211 Indoles Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D001777 Blood Coagulation The process of the interaction of BLOOD COAGULATION FACTORS that results in an insoluble FIBRIN clot. Blood Clotting,Coagulation, Blood,Blood Clottings,Clotting, Blood
D000925 Anticoagulants Agents that prevent BLOOD CLOTTING. Anticoagulant Agent,Anticoagulant Drug,Anticoagulant,Anticoagulant Agents,Anticoagulant Drugs,Anticoagulation Agents,Indirect Thrombin Inhibitors,Agent, Anticoagulant,Agents, Anticoagulant,Agents, Anticoagulation,Drug, Anticoagulant,Drugs, Anticoagulant,Inhibitors, Indirect Thrombin,Thrombin Inhibitors, Indirect
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D015842 Serine Proteinase Inhibitors Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES. Serine Endopeptidase Inhibitor,Serine Endopeptidase Inhibitors,Serine Protease Inhibitor,Serine Protease Inhibitors,Serine Proteinase Antagonist,Serine Proteinase Antagonists,Serine Proteinase Inhibitor,Serine Proteinase Inhibitors, Endogenous,Serine Proteinase Inhibitors, Exogenous,Serine Protease Inhibitors, Endogenous,Serine Protease Inhibitors, Exogenous,Antagonist, Serine Proteinase,Endopeptidase Inhibitor, Serine,Inhibitor, Serine Endopeptidase,Inhibitor, Serine Protease,Inhibitor, Serine Proteinase,Protease Inhibitor, Serine,Proteinase Antagonist, Serine,Proteinase Inhibitor, Serine
D015945 Factor XIa Activated form of factor XI. In the intrinsic pathway, Factor XI is activated to XIa by factor XIIa in the presence of cofactor HMWK; (HIGH MOLECULAR WEIGHT KININOGEN). Factor XIa then activates factor IX to factor IXa in the presence of calcium. Coagulation Factor XIa,Factor XI, Activated,Activated Factor XI,Blood Coagulation Factor XI, Activated,Contact Activation Product,Factor 11A,Factor Eleven A,Factor XIa, Coagulation

Related Publications

Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Macrocyclic factor XIa inhibitors.
September 2017, Bioorganic & medicinal chemistry letters,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Structure-Based Design of Macrocyclic Factor XIa Inhibitors: Discovery of the Macrocyclic Amide Linker.
February 2017, Journal of medicinal chemistry,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Factors affecting the evolution of factor XIa during blood coagulation.
May 1975, The Journal of laboratory and clinical medicine,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Structure-Based Design of Macrocyclic Coagulation Factor VIIa Inhibitors.
August 2015, Journal of medicinal chemistry,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Thrombosis: Targeting factor XIa.
November 2016, Nature reviews. Cardiology,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Evidence for factor IX-independent roles for factor XIa in blood coagulation.
December 2013, Journal of thrombosis and haemostasis : JTH,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Kinetics of the Factor XIa catalyzed activation of human blood coagulation Factor IX.
May 1984, The Journal of clinical investigation,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Inhibition of human blood coagulation factor XIa by C-1 inhibitor.
February 1988, Biochemistry,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Functional characterization of human blood coagulation factor XIa using hybridoma antibodies.
September 1985, The Journal of biological chemistry,
Stephen Hanessian, and Andreas Larsson, and Tomas Fex, and Wolfgang Knecht, and Niklas Blomberg
Coagulation procofactor activation by factor XIa.
July 2010, Journal of thrombosis and haemostasis : JTH,
Copied contents to your clipboard!