Somatostatin agonists

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, (I) wherein: A¹ is an optionally substituted D- or L-aromatic alpha-amino acid or optionally substituted D- or L-cyclo(C_3-6)alkylalanine; A² is an optionally substituted aromatic alpha-amino acid or optionally substituted cyclo(C_3-6)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 (C_1-6)alkyl; wherein each said optionally substituted aromatic alpha-amino acid and each said optionally substituted cyclo(C_3-6)alkylalanine is optionally substituted with one or more substituents each independently selected from the group consisting of halogen, NO₂, OH, CN, (C_1-6)alkyl, (C_2-6)alkenyl, (C_2-6)alkynyl, (C_1-6)alkoxy, Bzl, O-Bzl, and NR⁹R¹⁰, where R⁹ 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 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.