Patent GB-1064263-A (GB)
Title: Improvements in or relating to a pentacosapeptide
Inventor: BOISSONNAS ROGER
IPC: C07K14/695
Filed: 1964-06-16
Abstract: The peptide H-Ser-Tyr-Ser-Nle-Glu-His-Phe-Arg - Try - Gly - Lys - Pro - Val - Gly - Lys - Lys-Arg - Arg - Pro - Val - Lys - Val - Tyr - Pro - Val - NH2 and its acid addition salts are prepared by hydrolysing off the protecting groups from the N-trityl-Ne -formyl derivative and optionally forming the acid addition salt.  N - Tri - Ser - Tyr - Ser - Nle - Glu - His - Phe - Arg - Try - Gly - Lys (For) - Pro - Val - Gly - Lys (For) - Lys (For) - Arg - Arg - Pro - Val - Lys (For) - Val - Tyr - Pro - Val - NH2 (where For = formyl and Tri = trityl) is prepared by stepwise synthesis through the following compounds: (where CBO = carbobenzyloxy; CP = trichlorophenyl; Tos = Tosyl; and TB = t=butyl) CBO-Tyr(CBO)OCP; CBO-Lys (For)OCP; CBO-Arg(Tos)-OCP; CBO-Phe-OCP; CBO-Glu(OTB)-OCP; CBO-Try-Gly-OCP; CBO - Val - Gly - OCP; CBO - Val-OCP; CBO - Tyr (CBO) - Pro - Val - NH2; CBO - Tyr - Pro - Val - NH2; H - Tyr - Pro-Val - NH2 - HBr; CBO - Val - Tyr - Pro - Val-NH2; H - Val - Tyr - Pro - Val - NH2 - HBr; CBO - Lys (For) - Val - Tyr - Pro - Val - NH2; H - Lys (For) - Val - Tyr - Pro - Val - NH2; CBO - Arg(Tos) - ProOTB; CBO - Arg (Tos)-ProOH; H - Arg(Tos) - ProOH, HBr; CBO-Arg (Tos) - ProOH; H - Arg (Tos)-Arg (Tos) - ProOH,HBr; CBO - Lys (For) - Arg (Tos)-Arg (Tos)-ProOH; H-Lys (For)-Arg (Tos)-Arg (Tos)-ProOH; - ProOH, HBr; CBO - Lys (For) - Arg (Tos)-Arg (Tos) - ProOH; H-Lys (For)-Arg (Tos)-Arg(Tos)-ProOh, HBr; CBO - Lys (For) - Lys (For) - Arg (Tos) - Arg (Tos) - ProOH; H - Lys (For) - Lys (For) - Arg (Tos) - Arg (Tos) - ProOH, HBr; CBO - Val - Gly - Lys (For) - Lys (For)-Arg (Tos) - Arg (Tos) - ProOH; CBO - Val-Gly - Lys (For) - Lys (For) - Arg (Tos) - Arg (Tos)-Pro - Val - Lys (For) - Val - Tyr - Pro - ValNH2; H - Val - Gly - Lys (For) - Lys (For) - Arg (Tos)-Arg (Tos) - Pro - Val - Lys (For) - Val - Tyr-Pro - Val - NH2; H - Lys (For) - Pro - OTB, HAc; CBO - Try - Gly - Lys (For) - ProOTB; CBO - Arg (Tos) - Try - Gly - Lys (For) - Pro-OTB; H - Arg (Tos) - Try - Gly - Lys (For)-Pro - OTB; CBO - Phe - Arg (Tos) - Try - Gly-Lys (For) - Pro - OTB; H - Phe - Arg (Tos)-Try - Gly - Lys (For) - Pro - OTB; CBO - His-Phe - Arg (Tos) - Try - Gly - Lys (For) - Pro OTB; CBO - His - Phe - Arg (Tos) - Try - Gly-Lys (For) - ProOH; H - His - Phe - Arg (Tos)-Try - Gly - Lys (For) - ProOH;  CBO - Glu-(OTB) - His - Phe - Arg (Tos) - Try - Gly - Lys (For) - ProOH; CBO - Glu (OTB) - His - Phe-Arg (Tos) - Try - Gly - Lys (For) - ProOCP; CBO - Glu (OTB) - His - Phe - Arg (Tos) - Try-Gly - Lys (For) - Lys (For) - Arg (Tos) - Arg (Tos)-Pro - Val - Lys (For) - Val - Tyr - Pro - ValNH2; H - Glu - His - Phe - Arg (Tos) - Try - Gly - Lys (For) - Lys (For) - Arg (Tos) - Arg (Tos) - Pro-Val - Lys (For) - Val - Tyr - Pro - Val - NH2; Tri - Ser - TyrOMe; Tri - Ser - Tyr - NHNH2; CBO - Ser - Nle - OMe; H - Ser - Nle - OMe, HCl; Tri - Ser - Tyr - Ser - Nle - OMe; Tri-Ser - Tyr - Ser - NleNHNH2; Tri - Ser - Tyr-Ser - Nle - N3. Tri - (2,4,5 - trichloro - phenyl)-phosphite is also prepared.  Pharmaceutical compositions comprise the pentacosapeptides of the invention and a suitable inert carrier.  The compositions may be in a form suitable for oral, parenteral, enteral or intranasal administration.