Derivatives of peptides and peptide mimetics having integrin...

C - Chemistry – Metallurgy – 07 – K

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C07K 14/78 (2006.01) A61K 31/195 (2006.01) A61K 38/39 (2006.01) A61L 33/00 (2006.01) A61P 41/00 (2006.01) C07C 279/18 (2006.01) C07K 7/06 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2419469

The invention relates to compounds of formula (I) B-Q-X1, wherein B is a bioactive, cell adhesive mediating molecule, selected from the group (i) and Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (ii), Trp-Tyr-Lys-Ile-Ala-Phe- Gln-Arg-Asn-Arg-Lys (iii), Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (iv), Thr- Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg (v), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln- Arg-Asn (vi), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg (vii), wherein (i) X, Y, Z, R2, R3, R4, A, Ar, Hal, Het, Het1, n, m, o, p, q, s, t have the meanings cited in Claim 1, Q is absent or is an organic spacer molecule, X1 is an anchor molecule selected from the group cited in Claim 1, and the salts thereof, which can be used as integrin inhibitors particularly for treatment of illnesses, deficiencies and inflammations caused by implants and osteolytic illnesses such as osteoporosis, thrombosis, cardiac infarction and arteriosclerosis, in addition to the acceleration and strengthening of the integration process of implants or the biocompatible surface in tissue.

La présente invention concerne des composés de formule (1) B-Q-X¿1? dans laquelle B est une molécule bioactive établissant l'adhésion cellulaire, choisie parmi le groupe (i) et Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (ii), Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (iii), Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg-Lys (iv), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn-Arg (v), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg-Asn (vi), Thr-Trp-Tyr-Lys-Ile-Ala-Phe-Gln-Arg (vii). Selon l'invention, dans (i), X, Y, Z, R?2¿, R?3¿, R?4¿, A, Ar, Hal, Het, Het?1¿, n, m, o, p, q, s, t correspondent aux éléments indiqués dans la revendication 1, Q est manquant ou est une molécule organique d'espacement, X¿1? est une molécule d'ancrage choisie parmi le groupe indiqué dans la revendication 1. Selon l'invention, lesdits composés, ainsi que leur sels, peuvent être utilisés en tant qu'inhibiteurs d'intégrine notamment pour le traitement de maladies, lésions et inflammations provoqués par des implants, et de maladies ostéolytiques telles que l'ostéoporose, la thrombose, l'infarctus du myocarde et l'artériosclérose, ainsi que pour accélérer et amplifier le processus d'intégration de l'implant ou de la surface biocompatible dans le tissu.

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