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

• Main Author: MICHEL VEDEL, JOSEPH DIAZ ET CATHERINE CAZAUBON
• Format: Patent
• Language: English; French
• Published: 16.09.1983
• Subjects: CHEMISTRY; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEPTIDES; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

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. LA PRESENTE INVENTION CONCERNE DES ANALOGUES DE LA SOMATOSTATINE SUBSTITUES PAR L'AZAALANINE CARACTERISES EN CE QU'ILS REPONDENT A LA FORMULE GENERALE(CF DESSIN DANS BOPI)DANS LAQUELLE:-R DESIGNE UN H, UN ACIDE AMINE, UN DIPEPTIDE COMME ALA-GLY PAR EXEMPLE;-X (L) TRP OU (D) TRP;-X (L) THR, (D) PHE OU BIEN LIAISON SIMPLE;-X (L) SER OU LIAISON SIMPLE;-CYS (L)-CYS OU (D)-CYS;-AZA A REPRESENTE UNE STRUCTURE ACIDE A-AMINE NON NATUREL DANS LAQUELLE LE CARBONE ASSYMETRIQUE DE L'ALANINE A ETE REMPLACE PAR UN ATOME D'AZOTE(CF DESSIN DANS BOPI)ET LES SELS, PHARMACEUTIQUEMENT ACCEPTABLES, DE CES PRODUITS ET LES MEDICAMENTS EN CONTENANT.