Patent ID: 6355617
Filing Date: 2002-03-12
Classification: A61K,A61P,C07K,C12N

Abstract:
A peptide derivative of the formula I, Pâ€”R1â€”R2â€”R3â€”R4, or a pharmaceutically acceptable salt thereof, whereinP is a hydrophobic residue selected from: (a) an aliphatic, aromatic or mixed aliphatic/aromatic organic group of from 5 to 20 carbon atoms, or a heteroaromatic or aliphatic/heteroaromatic organic group of from 5 to 20 carbon atoms and 1, 2 or 3 heteroatoms selected from oxygen, sulfur and nitrogen; (b) an L-amino acid selected from phenylalanine and hydrogenated analogues thereof, para-chloroPhe, 3-(2-thienyl)alanine, tyrosine, Tyr(Omethyl), tryptophan, biphenylalanine, 3-(1-naphthyl)alanine, 3-(2-naphthyl)alanine and hydrogenated analogues thereof 3-(1-adamantyl)alanine, Glu(OBenzyl), 3-(benzyloxy)Ala, 3-(benzylsulfanl)Ala and 9-fluoroenylGly, each of which may optionally bear on the N-terminus a hydrophobic aliphatic, aromatic, heteroaromatic or mixed aliphatic/aromatic or aliphatic/heteroaromatic organic group as defined on (a); and (c) a sequence of L-amino acids selected from Ala-Cha, Ala-Ala-Cha, Tyr-Ala-Ala-Cha, Tyr-Ala-Ala-Phe, Ala-Phe-Phe-Phe and Ala-Ala-Ala-Phe, wherein the first amino acid may also be a D-amino acid and may also optionally bear a hydrophobic aliphatic, aromatic, heteroaromatic or mixed aliphatic/aromatic or aliphatic/heteroaromatic organic group as defined in (a); R1 is a sequence of 2 L-amino acids and R3 is a sequence of 4 L-amino acids; R2 is a group of formula II in which Ra is selected from hydrogen and (1-4C)alkyl and A methylene or oxygen; and R4 is OH, NH2 or 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 â€”A1â€”G1 in which A1 is (3-7C)alkylene or A1 is selected from (1) a group of the formula â€”A2â€”B2â€” 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 â€”A3â€”B3â€”C3â€” in which A3 is methylene, B3 is p-phenylene or 1,4-cyclohexylene and C3 is (1-3C)alkylene; and G1 a group of the formula â€”N&boxH;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 R4 is 1-piperazinyl, 4-methyl-1 piperazinyl, 4-amidino-1-piperazinyl, 4-(2-(2-hydroxyethoxy)ethyl)-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 R4 is a sequence of 1 to 6 amino acids or an amide thereof.