Patent GB-1097172-A (GB)
Title: Pentacosapeptide
Inventor: BOISSONNAS ROGER
IPC: A61K38/00
Filed: 1965-01-18
Abstract: The pentacosapeptide H - Ser - Tyr - Ser - Nle-Glu(OH) - His - Phe - Arg - Try - Gly - Lys - Pro-Val - Gly - Lys - Lys - Lys - Lys - Pro - Val-Lys -Val-Tyr-Pro-ValNH2 and its acid addition salts are prepared by condensing H-Val-Lys(R)-Val-Tyr-Pro-ValNH2 with Z-Val-Gly-Lys(R)-Lys(R)-Lys(R)-Lys(R)-Lys(R)-ProOCP, removing the Z-group from the resulting Z-Val-Gly-Lys(R)-Lys(R) - Lys(R) - Lys(R) - Pro - Val - Lys(R)-Val-Tyr-Pro-ValNH2 condensing the tridecapeptide with Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Try-Gly-Lys(R)-Pro-OCP, removing the terminal Tri-group from Tri-Glu(OtBu)-His(Tri)-Phe - Arg - Try - Gly - Lys(R) - Pro - Val - Gly-Lys(R) - Lys(R) - Lys(R) - Lys(R) - Pro - Val-Lys(R)-Val-Try-Pro-Val-NH2, condensing the eicosapeptide with R1-Ser-Tyr-Ser-NleN3 and removing in one or more processes the blocking groups R, Tri and R1, where R and R1 are N-blocking groups used in peptide chemistry especially the butoxycarbonyl (BOC) and tertamyloxy carbonyl (CAT) group.  Tri is triphenylmethyl, Z is carbobenzoxy, and CP is 2,4,5-trichlorophenyl.  The following intermediates and starting materials are prepared: Z-Lys(BOC)OCP; H-Val - Lys(BOC) - Val - Tyr - Pro - ValNH2; Z-Tyr - Pro - ValNH2; H - Tyr - Pro - Val - NH2-HBr; Z - Val - Tyr - Pro - Val - NH2; H - Val-Tyr - Pro - ValNH2HBr; Z - Lys(BOC) - Val-Tyr - Pro - Val - NH2; H - Lys(BOC) - Val - Tyr-Pro - Val - NH2HBr; Z - Lys(BOC) - ProOMe and its free acid; H-Lys(BOC)-Pro-OH; Z-Lys-(BOC) - Lys(BOC) - ProOH; H - Lys(BOC)-Lys(BOC) - ProOH; Z - Lys(BOC) - Lys(BOC)-OMe; Z - Val - Gly - Lys(BOC) - Lys(BOC)OMe; Z - Val - Gly - Lys(BOC) - Lys(BOC) - NHNH2 and its azide; Z-Val-Gly-Lys(BOC)-Lys(BOC)-Lys(BOC)-Lys(BOC)-ProOH and its -CP ester; Z - Arg(NO2) - Try - GlyOH and its -CP ester; Z - Arg(NO2) - Try - Gly - Lys(BOC) - Pro - OH - H - Arg - Try - Gly - Lys(BOC) - Pro - OH; Z-Glu(OtBu) - His - Phe - OMe; Tri - Glu(OtBu); His(Tri) - Phe - OMe and its hydrazide and azide; Tri - Glu(OtBu) - His(Tri) - Phe - Arg-Try - Gly - Lys(BOC) - ProOH and its -CP ester, HCl salt; Tri-Ser-Tyr-OMe and its hydrazide; Z - Ser - Nle-OMe; H - Ser - NleOMeHCl; Tri - Ser - Tyr - Ser - Nle - OMe and its hydrazide and azide; tert amyl-thiophenyl carbonate; tertamyl carbazate; Z-Lys(CAT)OH and its methyl and -CP esters; H - Val - Lys(CAT) - Val - Tyr-Pro-ValNH2 and its Z-derivative; H-Lys(CAT)-Val-Tyr-Pro-ValNH2 and its Z-derivative; H-Lys(CAT)-Pro-OH and its Z-derivative; H-Lys-(CAT) -Lys(CAT)-ProOH and its Z-derivative; Z - Lys(CAT) - Lys(CAT)OMe; Z - Val - Gly-Lys(CAT) - Lys(CAT)OMe and -NHNH2; Z - Val - Gly - Lys(CAT) - Lys(CAT) - Lys-(CAT) - Lys(CAT) - ProOH and its -CP ester; H - Val - Gly - Lys(CAT) - Lys(CAT) - Lys(CAT) - Lys(CAT) - Pro - Val - Lys(CAT) - Val-Tyr-Pro-ValNH2 and its Z-derivative; H-Arg-Try-Gly-Lys(CAT)-ProOH and its Z- and NO2-derivative and Tri-Glu(OtBu)-His(Tri)-Phe-Arg-Arg-Try-Gly-Lys(CAT)-ProOH and its -CP ester, HCl salt.  Pharmaceutical compositions comprise the pentacosapeptide or a salt thereof and a carrier. The compositions may be in a form suitable for enteral or parenteral administration.