CYCLOPEPTIDE DERIVATIVES WITH INTEGRIN INHIBITOR PROPERTIES

• Main Authors: MEYER, JORG, KESSLER, HORST, JONCZYK, ALFRED, FINSINGER, DIRK, KANTLEHNER, MARTIN, NIES, BERTHOLD
• Format: Patent
• Language: English; French
• Published: 12.02.2008
• Subjects: CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS, ORSURGICAL ARTICLES; CHEMISTRY; DISINFECTION, STERILISATION, OR DEODORISATION OF AIR; HUMAN NECESSITIES; HYGIENE; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS, OR SURGICALARTICLES; MEDICAL OR VETERINARY SCIENCE; METALLURGY; METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS INGENERAL; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

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- R1- NH-X]m, -[NH-R1-CO-]m, -[CO-R1-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-R1-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 selecte d 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(R8)-CH(R3)-COOH, and R1, R3, R8, m, n and p ha ve 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 surfac e in tissues.