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The present invention relates to a bicyclic inhibitor of the coagulation enzyme activated factor XII (FXIIa) comprising or consisting of the peptide (X1)(X2)(X3)n(X4)(X5)(X6)m(X7)(X9)l(X10)(X11)(X12)(X13)(X14)k(X15)(X16), wherein (X1) is present or absent and, if present, is an amino acid; (X2) is an amino acid with a side chain; (X3) is an amino acid and n is between 0 and 3, preferably 0 or 1 and most preferably 0; (X4) is an aliphatic L-amino acid or a cyclic L- amino acid, preferably L, P or an aromatic L-amino acid, and most preferably an aromatic L-amino acid; (X5) is an amino acid; (X6) is an amino acid and m is between 0 and 3, preferably 0 or 1 and most preferably 0; (X7) is an amino acid with a side chain; (X9) is an amino acid and I is between 0 and 3, preferably 0 or 1 and most preferably 0; (X10) is an amino acid; (X11) is an amino acid, preferably Q; (X12) is a hydrophobic L-amino acid, preferably an aliphatic L-amino acid, and is most preferably L; (X13) is an amino acid; (X14) is an amino acid and k is between 0 and 3, preferably 0 or 1 and most preferably 0, (X15) is an amino acid with a side chain; and (X18) is present or absent and, if present, is an amino acid; and wherein the side chains of (X2), (X7) and (X15) are connected via a connecting molecule, said connecting molecule having at least three functional groups, each functional group forming a covalent bond with one of the side chains of (X2), (X7) and (X15).
Tamar Kohn, Shotaro Torii, Aleksandar Antanasijevic
Luc Reymond, Fabien Kuttler, Milena Maria Schuhmacher, Daria Korotkova, Manon Sandra Bardyn, Triana Amen