Sulphur-free cyclic peptide somatostatin analogues - used for treating excessive secretion of growth hormone, insulin and glucagon

摘要

(A) Cyclic peptides of formula (I) and their acid addition salts and complexes are new (R is Asn or is absent; trp is D-Trp or L-Trp, opt. substd. in the benzene ring by halo or nitro gps.; W is a substituent on the benzene ring of the L-phenylalanine gp., and is opt. etherified OH, halogen or H; X is the residue of an omega-amino-lower alkane-mono- or dicarboxylic acid or is absent; Y is as X). (B) Intermediates of formula (II) and (III) (see "Preparation") and their acid addition salts are new. (I) have somatostatin-like activity, and can be used for treating diseases associated with excessive secretion of growth hormone, insuline or glucagon, e.g. acromegaly or juvenile diabetes. (I) have comparable activity with somatostatin, but are more easily synthesised, since they contain fewer aminoacid residues and no sulphur-contg. gps. Since (I) retain physiological activity when some of the optically active aminoacid residues of stomatostatin are replaced by simple optically inactive aminoacids, (I) require =7 optically active aminoacids for synthesis, cf. 13 for somatostatin. Daily dose is 0.1-120 mg/70 kg., generally by injection or intranasally.