Patent UA-61071-C2 (UA)
Title: Cyclopeptids, a method for preparing thereof, a pharmaceutical composition and a method for preparing the same
IPC: C07K14/75
Filed: 1997-04-02
Abstract: The invention concerns cyclopeptides of formula (I): Cyclo-(Arg-Gly-Asp-X-Y) in which ? is Cha, Nal, Phe, 2-R1-Phe, 3-R1-phe, 4-R1-Phe, homo-Phe, Phg, Thi, Trp, Tyr or derivatives of Tyr, whereby the OH group can be etherified by alkyl groups containing 1-18 C-atoms and the amino-acid groups given can also be derivatives, R1 is NH2. NO2, Br, Cl, F, alkyl with 1-18 C-atoms, Ar, Ar-O or 3H. ? is Gly in which the N-atom may be substituted by R2 and/or the C-atom may be substituted by R3 and/or R4, with the provision that Gly has at least one of the substituents specified, Ar is phenyl which may be substituted by one or two of the groups NH2. NC2, I, Br, Cl, F, alkyi with 1-6 C-atoms or 3H, R2, R3 or R4, independently of each other, are alkyl with 1-18 C-atoms or R2 and R3 or R3 and R4 together in each case are a branched or unbranched alkylene chain with 3 to 18 C-atoms so that either the N-atom and the C-atom together with the alkylene chain, or the C-atom alone, forms a ring with the alkylene chain, whereby, when optically active ammo-acid or amino-acid-derivative groups are involved, both the D- and the L-form are included, plus derivatives, in particular the -ester of aspartic acid or N-guanidine acyl derivatives of arginine or prodrug as well as their physiologically acceptable salts. These compounds act as integrin inhibitors and may be used particularly for the prophylaxis and treatment of circulatory and angiogenic conditions and microbial infections as well as in tumor therapy. The invention concerns cyclopeptides of formula (I): Cyclo-(Arg-Gly-Asp-X-Y) in which X is Cha, Nal, Phe, 2-R1-Phe, 3-R1-Phe, 4-R1-Phe, homo-Phe, Phg, Thi, Trp, Tyr or derivatives of Tyr, whereby the OH group can be by alkyl groups containing 1-18 C-atoms and the amino-acid groups given can also be derivatives, R1 is NH2, NO2, I, Br, Cl, F, alkyl with 1-18 C-atoms, Ar, Ar-O or 3H, Y is Gly in which the 'alpha' N-atom may be substituted by R2 and/or the 'alpha' C-atom may be substituted by R3 and/or R4, with the provision that Gly has at least one of the substituents specified, Ar is phenyl which may be substituted by one or two of the groups NH2, NO2, I, Br, Cl, F, alkyl with 1-6 C-atoms or 3H, R2, R3 or R4, independently of each other, are alkyl with 1-18 C-atoms or R2 and R3 or R3 and R4 together in each case are a branched or unbranched alkylene chain with 3 to 18 C-atoms so that either the 'alpha' N-atom and the 'alpha' C-atom together with the alkylene chain, or the 'alpha' C-atom alone, forms a ring with the alkylene chain, whereby, when optically active amino-acid or amino-acid-derivative groups are involved, both the D- and the L-form are included, plus derivatives, in particular the 'beta'-ester of aspartic acid or N-guanidine acyl derivatives of arginine or prodrug as well as their physiologically acceptable salts. These compounds act as integrin inhibitors and may be used particularly for the prophylaxis and treatment of circulatory and angiogenic conditions and microbial infections as well as in tumor therapy.