STUDY OF COUMARINS WITH IMPROVED SOLUBILITY TO INHIBIT FXIIa, AN EMERGING TARGET IN THROMBOSIS RESEARCH

Charlotte Bouckaert, Christelle Vancraeynest, Eduard Dolušić, Raphaël Frédérick, Lionel Pochet

Résultats de recherche: Contribution à un événement scientifique (non publié)Poster

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Résumé

Thrombotic diseases, in which a deregulated haemostatic activity occurs, remain a major concern in medicine. Anticoagulants are part of the strategies to address these disorders. However current available drugs are still associated with risk of severe bleeding complications and thus, novel antithrombotics are required1.

In this perspective, coagulation factor XIIa (FXIIa), a serine protease implicated in the coagulation cascade, recently emerged as a promising target in the development of such agents2. Indeed, it was demonstrated that FXII deficiency or inhibition protects against thrombosis without causing spontaneous bleeding in mice3.

Based on these considerations, the aim of our project is to develop novel selective FXIIa inhibitors to detail the exact role of this enzyme in thrombotic diseases. These compounds could also be a good starting point for the development of new antithrombotic drugs.

The 3-carboxamide coumarins (figure 1) are to date the only nonpetidic and selective inhibitors of FXIIa described in literature4. However, their low solubility and poor pharmacokinetics resulted in a lack of activity in in vivo models of thrombosis. As consequence, we need to improve these characteristics while keeping the selectivity and potency towards FXIIa.

In this work, we first synthesized new coumarins with improved solubility. Their inhibition potency was then measured on FXIIa and finally, their stability was evaluated.
langue originaleAnglais
PagesBook of Abstracts, MedChem 2012, Château de Colonster, Liège - November 30, 2012, P01
Nombre de pages1
Etat de la publicationPublié - 30 nov. 2012
EvénementAnnual One-Day Symposium on Medicinal Chemistry of SRC & KVCV (Medchem 2012) - Liège, Belgique
Durée: 30 nov. 2012 → …

Colloque

ColloqueAnnual One-Day Symposium on Medicinal Chemistry of SRC & KVCV (Medchem 2012)
PaysBelgique
La villeLiège
période30/11/12 → …

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    Annual One-Day Symposium on Medicinal Chemistry of SRC & KVCV (Medchem 2012)

    Eduard Dolusic (Orateur)

    30 nov. 2012

    Activité: Types de Participation ou d'organisation d'un événementParticipation à une conférence, un congrès

    Thèses de l'étudiant

    Conception, synthèse et évaluation biologique de coumarines en tant qu'inhibiteurs de protéases à sérine

    Author: Pochet, L., 2000

    Superviseur: Masereel, B. (Promoteur)

    Thèse de l'étudiant: Doc typesDocteur en Sciences

    Etude du mode de liaison de composés coumariniques, inhibiteurs de thrombine

    Author: De Ruyck, J., 2004

    Superviseur: Durant, F. (Promoteur)

    Thèse de l'étudiant: Master typesMaster en sciences chimiques

    Evaluation biologique de coumarines en tant qu'inhibiteurs de protéases à sérine de la cascade de la coagulation

    Author: Robert, S. H., 2004

    Superviseur: Masereel, B. (Promoteur) & Pochet, L. (Copromoteur)

    Thèse de l'étudiant: Master typesMaster en sciences biologiques

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    Bouckaert, C., Vancraeynest, C., Dolušić, E., Frédérick, R., & Pochet, L. (2012). STUDY OF COUMARINS WITH IMPROVED SOLUBILITY TO INHIBIT FXIIa, AN EMERGING TARGET IN THROMBOSIS RESEARCH. Book of Abstracts, MedChem 2012, Château de Colonster, Liège - November 30, 2012, P01. Poster présenté � Annual One-Day Symposium on Medicinal Chemistry of SRC & KVCV (Medchem 2012), Liège, Belgique.