| abstract |
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-A?3-A4-Cys}-A5-Y1¿, wherein: A1 is an optionally substituted D- or L-aromatic α-amino acid or optionally substituted D- or L-cyclo(C¿3-6?)alkylalanine; A?2¿ is an optionally substituted aromatic α-amino acid or optionally substituted cyclo(C¿3-6?)alkylalanine; A?3¿ is Lys or Orn; A4 is β-Hydroxyvaline, Ser, hSer, or Thr; A5 is β-Hydroxyvaline, Ser, hSer, or Thr; and Y1 is OH, NH¿2? or NHR?1¿, where R1 is (C¿1-6?) alkyl; wherein each said optionally substituted aromatic α-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 NR?9R10¿, where R?9 and R10¿ each is independently H or (C¿1-6?) alkyl; and wherein the amine nitrogen of each peptide bond and the amino group of A?1¿ 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-NH¿2?; or a pharmaceutically acceptable salt thereof. |