SOMATOSTATIN AGONISTS

摘要

The present invention is directed to cyclic peptides of formula (I): X-A1-cyclo(D-Cys-A?3-A4-Lys-A6-A7)-A8¿-Y, or a pharmaceutically acceptable salt thereof, wherein X is H, formula (a) or formula (b); A?1 and A3¿ 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; A4 is L-Trp, D-Trp, L-β-methyl-Trp or D-β-methyl-Trp; A6 is -NH-(CHR1)n-CO-, where n is 2, 3, or 4; A7 is L- or D-Cys; A8 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 NR2R3 where R?2 and R3¿ are each independently H or (C¿1?-C5)alkyl; R?1¿ is selected from the group consisting H, (C¿1?-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?4R5¿), -COOH, -CON(R4R5), halo, -OH, -CN, and -NO¿2?; R?4 and R5¿ each is, independently for each occurrence, H or (C¿1-3?)alkyl; where the Cys of A?2¿ is bonded to the Cys of A7 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.