CYCLOPEPTIDE DERIVATIVES WITH INTEGRIN INHIBITOR PROPERTIES

摘要

The invention relates to compounds of formula (I), R-Q-X, wherein R = cyclo-(Arg-Gly-Asp-Z), whereby Z is bonded in a side chain to Q or to Z if Q is lacking, Q is lacking and represents -[CO-R<1>-NH-X]m, -[NH-R<1>-CO-]m, -[CO-R<1>-CO-]m, -(CO-CH2-O-CH2CH2-O-CH2CH2-NH-)n, -(NH-CH2-O-CH2CH2-O-CH2CH2-CO-)n, -(NH-CH2CH2-O-CH2CH2-O-CH2-CO-)n or -(CO-CH2-O-CH2CH2-O-CH2-CH2-NH-)n-[CO-R<1>-NH-]m, X = -CO-CH=CH2, -CO-C(CH3) = CH2, -NH-CH = CH2, -NH-C(CH3)=CH2 or -NH-(CH2)p-SH, Z means, independently from each other, an amino acid radical or a dipeptide or tripeptide radical, whereby the amino acids, independently from each other, are selected from a group consisting of Ala, Asn, Asp, ARg, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, Val or M, whereby the above-mentioned amino acids can also be derivatized, and the amino acid radicals are linked to each other like peptides by the alpha amino and alpha carboxy groups, and whereby m is always contained, M = NH(R<8>)-CH(R<3>)-COOH, and R<1>, R<3>, R<8>, m, n and p have the meanings cited in claim 1, in addition to the salts thereof, whereby said substances can be used as integrin inhibitors, especially in the treatment of implant-induced diseases, defects, inflammations and osteolytic diseases such as osteoporosis, thrombosis, cardiac infarction, and arteriosclerosis, in addition to accelerating and amplifying the integration process of an implant or biocompatible surface in tissues.