Patent ES-316390-A1 (ES)
Title: Peptides having an adrenocorticotropic hormone action and process for their manufacture
IPC: A61K38/22
Filed: 1965-08-11
Abstract: A peptide that differs from an ACTH-active peptide containing 16-39 amino acid residues and having an N-terminal amino acid residue with L-configuration, solely in that the N-terminal amino acid residue has D-configuration, acid addition salts, complexes and amino and carboxylic acid blocked derivatives thereof are prepared by standard methods of peptide synthesis. Preferred peptides are those that differ from an (all-L)-ACTH-active peptide containing a 16-39 amino acid residue sequence (commencing at the N-terminus) of a natural corticotrophin, in which at least one of the amino acid residues in the positions 1 to 5, 17, 18 and 25 to 33 may be replaced by the residue of another natural a -amino acid or of a homologue thereof, solely in that the N-terminal amino acid residue has D-configuration. The following compounds are prepared as starting materials or as intermediates: BOC-D-Serine, BOC - D - Ser - Tyr - Ser - Met - OMe and -NHNH2 BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - GlyOH BOC - D - Ser - Tyr+ - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu BOC - D - alanine BOC - D - Ala - Tyr - Ser - Met - NHNH2 BOC - D - Ala - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - GlyOH BOC - D - Ala - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu Z - Arg - Pro - OtBu Z - Arg - Arg - Pro - OtBu H-Arg - Arg - Pro -OtBu Z - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - OtBu H - Lys(BOC) - Pro - Val - Gly - Lys - Lys(BOC) - Arg - Arg - Pro OtBu BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - OtBu Z - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu H - Pro - Val - Lys - Val - Tyr - Pro OtBu Z - Orn(BOC) - OH its p-nitrophenyl ester and its hydrophthalimide ester Z - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu H - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu Z - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBOC H - Orn(BOC) - Orn(BOC) - Pro - Val - Lys (BOC) - Val - Tyr - Pro - OtBu Z - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys (BOC) - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Orn - Tyr - Pro OtBu H - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro OtBu - tosylate BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys - (BOC) - Lys(BOC) - Orn(BOC) - Orn(BOC) - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu H - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - NH2 BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - NH2 BOC - D - Ser - Tyr - Ser - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - ProVal - Lys(BOC) - Val - Tyr - Pro - Asp(OtBu) - Gly - Ala - Glu(OtBu) - Asp(OtBu) - Glu(NH2) - Leu - Ala - Glu(OtBu) - Ala - Phe - Pro - Leu - Glu(OtBu) - Phe - OtBu BOC - Tyr - Gly - Ome H - Tyr - Gly - Ome, HCl BOC - D - Ser - Tyr - Gly - Ome BOC - D - Ser - Tyr - Gly - OH BOC - D - Ser - Tyr - Gly - Met - Ome and -NHNH2 Z - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) - Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu - triacetate H - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu - tetra-acetate and BOC - D - Ser - Tyr - Gly - Met - Glu(OtBu) - His - Phe - Arg - Try - Gly - Lys(BOC) - Pro - Val - Gly - Lys(BOC) Lys(BOC) - Arg - Arg - Pro - Val - Lys(BOC) - Val - Tyr - Pro - OtBu. Pharmaceutical compositions comprise the peptides of the invention in admixture or in conjunction with a suitable carrier. The compositions may be formulated for enteral or parenteral administration.