Somatostatin analogues having different activity profiles - inhibit growth hormone, insulin and glucagon secretion, with reduced effect on gastric secretion

摘要

Somatostatin analogues of formula (I) and their acid addition salts are new. (where R is H, an aminoacid or a dipeptide e.g. Ala-Gly; X1 is (L) trp or (I) Trp; X2 is (L) Thr, (D) Phe or a bond; X3 is (L) Ser or a bond; Cys is (L) Cys or (D) Cys and AzaA is a non-natural, alpha aminoacid gp. in which the metric C atom of alanine is replaced by N, i.e. NH = N(CH3)-CO-). PHE is Phe. This is not in formula as printed but covers most claimed cpds. (I) regulate the secretion of insulin, glucagon and growth. hormone and may be used to regulate glycemic levels in insulin dependent and non-insuling dependent diabetes and to control acromegalia. Unlike somatostatin, (I) have little effect on gastric secretion and are resistant to proteolysis (due to presence of -NH-NCCH3)-CO and the D-aminoacids) by resistant bacterial strains. The activity profile of the cpds. differs from that of somatostatin and each other and suitable cpds. can be selected to give the required activity. (I) are administered as 1-5% solns. by intravenous, intramuscular or sub-cutaneous injection in doses of 0.1-10 mg.