Histogranin peptide and their analgesic use

A compound or Formula I:

• 10
• wherein
• R1 represents hydrogen, alkyl, alkenyl, alkynyl, —(CH2)n—NH2, —(CH2)n—NH—C(═NH)NH2, or
• 11
• wherein
• “n” is an integer from 0 to 10;
• R2 represents —(CH2)nCONH2, wherein “n” represents an integer from 0 to 10;
• R3 represents hydrogen, alkyl, alkenyl, alkynyl, the radical of formula:
• 12
• or the radical of formula:
• 13
• wherein
• “n” represents an integer from 0 to 10;
• and
• R11, R12 and R13 may be the same or different and represent hydrogen, alkyl, alkenyl, alkynyl, —I, —F, —Br, —Cl, or —OH;
• and
• R4 represents —(CH2)nNH2, —(CH2)nNHC(═NH)NH2, or
• 14
• wherein
• “n” represents an integer from 0 to 10;
• R5 and R9 may be the same or different and represent hydrogen, alkyl, alkenyl, alkynyl, alkylcarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, dialkylamino, or —(CH2)naryl, wherein “n” is an integer from 1 to 10;
• R6, R7, and R8 may be the same or different and represent hydrogen, alkyl, alkenyl, or alkynyl;
• R10 represents hydroxy, alkoxy, alkenyloxy, alkynyloxy, amino, alkylamino, dialkylamino, alkylaryl, arylalkoxy, aryloxy, alkoxyaryl, A1, A1-A2, A1-A2-A3, A1-A2-A3-A4, or A1-A2-A3-A4-A5,
• wherein
• A1 represents threonine or serine;
• A2 represents leucine, glycine, alanine, valine, or isoleucine;
• A3 represents tyrosine, phenylalanine, or tryptophan;
• A4 represents glycine, alanine, leucine, isoleucine, or valine;
• and
• A5 represents phenylalanine, tyrosine, or tryptophan;
• pseudopeptide analogues thereof wherein ore or more of the carbonyl groups of the peptide linkage is replaced by —C(═S)— or by —CH2—, and/or wherein one or more of the amide bonds, —C(O)—NH—, is replaced by the retro-verso form, —NH—C(O)—, thereof;
• and
• pharmaceutically acceptable salts and esters thereof,
• with the proviso that the compound is not selected from the group comprising:
• 12 H-glycine-glutamine-glycine-arginine-threonine-leucine-tyrosine-glycine-phenylalanine-OH H-valine-glutamine-tryptophan-lysine-OH H-histidine-asparagine-leucine-lysine-OH H-leucine-glutamine-ψ(CS-NH)leucine-lysine-OH H-lysine-glutamine-phenylalanine-lysine-OH H-glycine-glutamine-leucine-lysine-OH