| 摘要 |
Claimed are a series of somatostatin agonists typically characterized by alkylation of the amide nitrogen, and uses thereof. Examples of claimed compounds are those according to formula (I), A1-cyclo{Cys-A2-D-Trp-A3-A4-Cys}- A5-Y1, wherein: A1 is an optionally substituted D- or L-aromatic .alpha.-amino acid or optionally substituted D- or L-cyclo(C3-6)alkylalanine; A2 is an optionally substituted aromatic .alpha.-amino acid or optionally substituted cyclo(C3-6)alkylalanine; A3 is Lys or Orn; A4 is .beta.-Hydroxyvaline, Ser, hSer, or Thr; A5 is .beta.-Hydroxyvaline, Ser, hSer, or Thr; and Y1 is OH, NH2 or NHR1, where R1 is (C1-6) alkyl; wherein each said optionally substituted aromatic .alpha.-amino acid and each said optionally substituted cyclo(C3-6) alkylalanine is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO2, OH, CN, (C1- 6)alkyl, (C2-6)alkenyl, (C2-6)alkynyl, (C1-6)alkoxy, Bzl, O-Bzl, and NR9R10, where R9 and R10 each is independently H or (C1-6) alkyl; and wherein the amine nitrogen of each peptide bond and the amino group of A1 of formula (I) is optionally substituted with a methyl group, provided that there is at least one said methyl group; and further provided that said compound is not D-Phe- cyclo{Cys-Phe-D-Trp-Lys-(N-Me-Thr)-Cys}-Thr-NH2; or a pharmaceutically acceptable salt thereof.
|
