Peptide derivatives

A peptide derivative of the formula I,

• P-AA1-AA2-AA3-AA4-AA5-AA6-AA7-AA8-Q
• or a pharmaceutically acceptable salt thereof, wherein
• P is a hydrophobic residue;
• AA1, AA2, AA3, AA4, AA5, AA6, AA7 and AA8 are L-amino acid residues in which 1, 2 or 3 of AA1, AA2 and AA3 are selected from a residue of the L-amino acid of formula II
• 18
• wherein n is an integer 1, 2, 3 or 4;
• X is —NH—CO—, —CO— or —O.CO—;
• R1 and R2 are selected from (A), (B) and (C) wherein
• (A) is a group of the formula —(CH2)a—CO—N(R3)(R4) in which a is an integer 1 or 2 and R3 and R4 are independently selected from a group —[(CH2)bO]m—Ra in which Ra is methyl or ethyl and m is an integer 1, 2, 3, 4 or 5;
• when m is 1, b is 2 or 3 and when m is 2, 3, 4 or 5, the value of b in each —(CH2)bO— unit is independently selected from 2 and 3;
• (B) is a group of the formula —(CH2)cO(CH2)d—CO—N(R5)(R6) in which c is an integer 2 or 3, d is an integer 1, 2 or 3 and R5 and R6 are independently selected from a group —[(CH2)eO]p—Rb in which Rb is methyl or ethyl and p is an integer 1, 2, 3, 4 or 5;
• when p is 1, e is 2 or 3 and when p is 2, 3, 4 or 5, the value for e in each —(CH2)eO— unit is independently selected from 2 and 3;
• and
• (C) is a group of the formula —[(CH2)fO]g—R7 in which R7 is methyl or ethyl and g is an integer 1, 2, 3, 4 or 5;
• when g is 1, f is 2 or 3 and when g is 2, 3, 4 or 5, the value for f in each—(CH2)fO— unit is independently selected from 2 and 3;
• or AA1, AA2, AA3, AA6, AA7, and AA8 are L-amino acid residues in which one or both of AA1 and AA7 are selected from a residue of the L-amino acid of formula II as defined above and AA4 together with AA5 form a group of the formula III, IIIa, IV or IVa;
• 19
• in which Ra, Rb and Rz are independently selected from hydrogen and (1-4C)alkyl, and A is oxygen or methylene;
• or AA1, AA2, AA3, AA4, AA5 and AA8 are L-amino acid residues in which one or both of AA1 and AA4 are selected from a residue of the L-amino acid of formula II as defined above and AA6 together with AA7 form a group of the formula III, IIIa, IV or IVa as defined above;
• and Q is OH, NH2, NRcRd wherein Rc is selected from (1-4C)alkyl, 2-carbamoylcyclopentyl, 2-pyridylmethyl, 4-carbamoylcyclohexyl, 4-carbamoylcyclohexylmethyl, 3-carbamoylphenyl, 4-carbamoylphenyl, 4-(carbamoylmethyl)phenyl, 4-(carboxymethyl)phenyl, 2-morpholinoethyl and a group of the formula -A1-G1 in which A1 is (3-7C)alkylene or
• A1 is selected from
• (1) a group of the formula -A2-B2-in which A2 is p-phenylene or 1,4-cyclohexylene and B2 is (1-4C)alkylene or A2 is methylene and B2 is p-phenylene or 1,4-cyclohexylene;
• and
• (2) a group of the formula -A3-B3-C3-in which A3 is methylene, B3 is p-phenylene or 1,4-cyclohexylene and C3 is (1-3C)alkylene;
• and
• G1 is a group of the formula —N═C[N(Rp)2]2 in which each Rp is independently selected from hydrogen, methyl, ethyl and propyl;
• and Rd is hydrogen or (1-4C)alkyl;
• or Q is 1-piperazinyl, 4-methyl-1-piperazinyl, 4-(2-(2-hydroxyethoxy)ethyl)-1-piperazinyl, 4-amidino-1-piperazinyl, 1-piperidyl or 4-substituted-1-piperidyl wherein the 4-substituent is selected from carboxy, carbamoyl, N-(2-aminoethyl)carbamoyl and N-(4-aminobutyl)carbamoyl;
• or Q is a sequence of 1 to 6 amino acid residues or an amide thereof.