Patent IL-65937-A (IL)
Title: Peptides related to corticotropin releasing factor and analogs thereof and pharmaceutical compositions containing them
IPC: C07K14/00
Filed: 1982-06-01
Abstract: 1. Claims for the contracting states : BE, CH, DE, FR, GB, IT, LI, LU, NL, SE A compound having the formula : Z-R1 -Pro-Pro-Ile-Ser-R8 -Asp-Leu-R11 -R12 -R13 - Leu-Leu-Arg-R17 -R18 -R19 -Glu-R21 -R22 -Lys-R24 -R25 - R26 -R27 -R28 -Gln-Gln-Ala-R32 -R33 -Asn-Arg-R36 - Leu-Leu-Asp-R40 -R41 -NH2 or a nontoxic addition salt thereof : wherein Z is an acyl group having 7 or less carbon atoms or hydrogen ; R1 is Ser-Gln-Glu or pGlu-Gly or Gln-Glu or Glu or D-Ser-Gln-Glu or D-pGlu-Gly or des R1 ; R8 ; R12 , R19 , R24 and R40 are selected from the group consisting of Leu, Ile, Ala, Gly, Val, Nle, Phe and Gln ; R11 is Thr or Ser ; R13 is His, Tyr or Glu ; R17 is Glu or Lys ; R18 is Val or Met ; R21 is Met, Met(O), Ile, Ala, Leu, Gly, Nle, Val, Phe or Gln ; R22 is Thr or Glu ; R25 is Asp or Glu ; R26 is Gln or Lys ; R27 is Leu, Ile, Ala, Gly, Val, Nle, Phe, Asp, Asn, Gln or Glu ; R28 is Ala or Lys ; R32 is His, Tyr or Ala ; R33 is Ser, Asn, Thr or Ala ; R36 is Lys or Leu ; R41 is Ala, Ile, Gly, Val, Leu, Nle, Phe, Gln or des R41 , provided however that when R13 is His, then R17 is Glu, R18 is Val, R22 is Thr, R26 is Gln, R28 is Ala, and R36 is Lys ; and provided that when R13 is Glu, R17 is Lys, R18 is Met, R22 is Glu, R26 is Lys, R28 is Lys, R32 is Ala and R36 is Leu, then either R1 is not pGlu-Gly or R8 is not Ile or R11 is Thr or R12 is not Leu or R9 is not Ile or R21 is not Ile or R24 is not Gln or R7 is not Glu or R33 is not Asn or R40 is not Thr or R41 is not Ile and provided further that Z may optionally include 1 to 10 amino acids. 1. Claims for the contracting state : AT A process for the manufacture of a peptide-compound comprising : (a) forming a peptide intermediate having the formula : X**1 -R1 -Pro-Pro-Ile-Ser(X**2 )-R8 -Asp(X**5 )-Leu-R11 (X**2 )-R12 -R13 -Leu-Leu-Arg(X**3 )-R17 -R18 -R19 - Glu(X**5 )- R21 -R22 -Lys(X**6 )-R24 -R25 -R26 -R27 -R28 -Gln(X**4 )- Gln(X**4 )-Ala-R32 -R33 -Asn(X**4 )-Arg(X**3 )- R36 -Leu-Leu-Asp (X**5 )-R40 -R41 -X**7 wherein R1 is Ser-Gln-Glu or pGlu-Gly or Gln-Glu or Glu or D-Ser-Gln-Glu or D-pGlu-Gly or des R1 ; R8 , R12 , R19 , R24 and R40 are selected from the group consisting of Leu, Ile, Ala, Gly, Val, Nle, Phe and Gln ; R11 is Thr or Ser ; R13 is His, Tyr or Glu ; R17 is Glu or Lys ; R18 is Val or Met ; R21 is Met, Met(O), Ile, Ala, Leu, Gly, Nle, Val, Phe or Gln ; R22 is Thr or Glu ; R25 is Asp or Glu ; R26 is Gln or Lys ; R27 is Leu, Ile, Ala, Gly, Val, Nle, Phe, Asp, Asn, Gln, or Glu ; R28 is Ala or Lys ; R32 is His, Tyr or Ala ; R33 is Ser, Asn, Thr or Ala ; R36 is Lys or Leu ; R41 is Ala, Ile, Gly, Val, Leu, Nle, Phe, Gln or des R41 , provided however that when R13 is His, then R17 is Glu, R18 is Val, R22 is Thr, R26 is Gln, R28 is Ala, and R36 is Lys ; and provided that when R13 is Glu, R17 is Lys, R18 is Met, R22 is Glu, R26 is Lys, R28 is Lys, R32 is Ala and R36 is Leu, then either R1 is not pGlu-Gly or R8 is not Ile or R11 is Thr or R12 is not Leu or R19 is not Ile or R21 is not Ile or R24 is not Gln or R27 is not Glu or R33 is not Asn or R40 is not Thr or R41 is not Ile, and wherein : X**1 is hydrogen or an alpha-amino protecting group ; X**2 is hydrogen or a protecting group for the alcoholic hydroxyl group of a Ser or Thr residue ; X**3 is hydrogen or a protecting group for the guanidino group of Arg ; X**4 is hydrogen or a protecting group for the amido group of Gln or Asn ; X**5 is hydrogen or a protecting group for the carboxyl group of Asp or Glu ; X**6 is hydrogen or a protecting group for the side chain amino group of Lys ; X**7 is selected from the class consisting of OH, OCH3 , esters, amides, hydrazides, -O-CH2 -polystyrene resin support and -O-CH2 -benzyl-polystyrene resin support ; provided that not all of X**1 to X**7 are hydrogen or OH, (b) removing protecting groups and optional covalently bound resin support from said polypeptide intermediate to provide a polypeptide and, if desired converting such resulting polypeptide into a nontoxic salt thereof.