| 摘要 |
The present invention is directed to cyclic peptides of formula (I): X-A<1>-cyclo(D-Cys-A<3>-A<4>-Lys-A<6>-A<7>)-A<8>-Y, or a pharmaceutically acceptable salt thereof, wherein X is H, formula (a) or formula (b); A<1> and A<3> are each independently the D- or L-isomer of an amino acid selected from the group consisting of Phe, Tyr, Tyr(I), Trp, 3-Pal, 4-Pal, Cpa and Nal; A<4> is L-Trp, D-Trp, L- beta -methyl-Trp or D- beta -methyl-Trp; A<6> is -NH-(CHR<1>)n-CO-, where n is 2, 3, or 4; A<7> is L- or D-Cys; A<8> is the D- or L-isomer of an amino acid selected from the group consisting of Phe, Tyr, Tyr(I), Trp, Nal, Cpa, Val Leu, Ile, Ser and Thr; Y is NR<2>R<3> where R<2> and R<3> are each independently H or (C1-C5)alkyl; R<1> is selected from the group consisting H, (C1-C4)alkyl and -CH2-aryl; wherein said aryl is an optionally substituted moiety selected from the group consisting of phenyl, 1-naphthyl, and 2-naphthyl, wherein said optionally substituted moiety is optionally substituted with one or more substituents each independently selected from the group consisting of (C1-6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, aryl, aryl(C1-6)alkyl, (C1-6)alkoxy, -N(R<4>R<5>), -COOH, -CON(R<4>R<5>), halo, -OH, -CN, and -NO2; R<4> and R<5> each is, independently for each occurrence, H or (C1-3)alkyl; where the Cys of A<2> is bonded to the Cys of A<7> by a di-sulfide bond formed from the thiol groups of each Cys; pharmaceutical compositions comprising said peptides and the use thereof as a somatostatin receptor subtypes agonist. The peptides of the present invention bind selectively to the somatostatin subtype receptor type-5 and elicit an agonist effect from the somatostatin subtype receptors that the peptides bind to. |
