Peptides and therapeutic applications thereof

Peptide derivatives having the general formula:

• Tyr--A--Gly--B--C--D (I)
• in which:
• A is a D.Ser, D.Thr, D.Cys, .beta.Phe Ser, .alpha.OH Leu, 4OH Ile or .alpha.,.beta.,.gamma. OHNor Val residue in which the side-chain OH or SH groups may be free or protected by (i) an unsubstituted benzyl radical or a benzyl radical substituted with one or more fluorine atoms, (ii) an aliphatic acyl radical having 1-6 carbon atoms or
• an acyl radical of the formula COX in which X is a phenyl, benzyl or benzhydryl radical, optionally substituted with one or more fluorine atoms,
• B is a L.Phe, pF.L.Phe or pentafluoro L.Phe residue,
• C is a Leu, N.Leu or Ile residue having D or L configuration,
• D represents a group of the formula:
• ##STR11## in which n=0 or 1, R is a hydrogen atom or a radical as defined for the protection of the OH group of residue A,
• Y is a hydrogen atom, a carboxy, carbamoyl oxy group, a group COOR.sub.1 or CONHR.sub.1 in which R.sub.1 represents an alkyl radical having 1-4 carbon atoms or a radical such as defined for the protection of the OH group of residue A, a phosphatidylethanolamine chain, or a chain ##STR12## in which n is an integer from 0 to 3 and R.sub.2 is a straight alkyl radical containing 1-4 carbon atoms,
• and their pharmaceutically acceptable salts.

Therapeutic composition having in particular analgesic, psychotropic and anti-diarrheic activities, comprising, as active ingredient, an effective amount of a peptide derivative having the formula:

• Tyr--A--Gly--B--C--D (I)
• in which:
• A is a D.Ser, D.Thr, D.Cys, homo Serine, .beta.Phe Ser, .beta.OH Leu, 4OH Ile, .alpha.,.beta.,.gamma. OHNor Val or OH Val residue in which the side-chain OH or SH groups may be free or protected by (i) a straight-or branched-chain alkyl radical having 1-6 carbon atoms, (ii) an unsubstituted phenyl radical or a phenyl radical substituted with one or more fluorine atoms, (iii) an unsubstituted benzyl radical or a benzyl radical substituted with one or more fluorine atoms, (iv) an aliphatic acyl radical having 1-6 carbon atoms or an acyl radical of the formula COX in which X is a phenyl, benzyl or benzhydryl radical, optionally substituted with one or more fluorine atoms,
• B is a L.Phe, pF.L.Phe or pentafluoro L.Phe residue,
• C is a Leu, N.Leu or Ile residue having D or L configuration,
• D represents a group of the formula:
• ##STR13## in which n=0, 1 or 2, R is a hydrogen atom or a radical as defined for the protection of the OH group of residue A,
• Y is a hydrogen atom, a hydroxy, carboxy, carbamoyl oxy group, a group OR.sub.1, COOR.sub.1 or CONHR.sub.1 in which R.sub.1 represents a radical such as defined for the protection of the OH group of residue A, a phosphatidylethanolamine chain, or a chain ##STR14## in which n is an integer from 0 to 3, R.sub.2 is a hydrogen atom or a straight alkyl radical containing 1-4 carbon atoms, and R.sub.3 is a hydrogen or oxygen atom or a straight alkyl residue having 1-4 carbon atoms
• and its pharmaceutically acceptable salts.