Patent ID: 6541453
Filing Date: 2003-04-01
Classification: A61K,A61P,C07K,Y10S

Abstract:
A peptide derivative of the formulaP-AA1-AA2-AA3-II-AA5-IIIa-AA8-Q or a pharmaceutically acceptable salt thereof, whereinP is a hydrophobic residue; AA1, AA2, AA3, AA5, and AA8 are L-amino acid residues; II is a residue of an L-amino acid of formula II â€ƒwherein n is an integer 1, 2, 3 or 4; X is â€”NHâ€”COâ€”, â€”CCâ€” or â€”OCOâ€”; R1 and R2 are selected from (A), (B) and (C) wherein A) is a group of the formula â€”(CH2)aâ€”COâ€”N(R3)(R4) in which a is an integer 1 or 2 and R3 and R4 are independently selected from a group â€”{(CH2)bO}mâ€”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 â€”(CH2)bOâ€” unit is independently selected from 2 and 3; (B) is a group of the formula â€”(CH2)cO(CH2)dâ€”COâ€”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 â€”{(CH2)eO}pâ€”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 â€”(CH2)eOâ€” unit is independently selected from 2 and 3; and (C) is a group of the formula â€”{(CH2)fO}gâ€”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 â€”(CH2)fOâ€” unit is independently selected from 2 and 3; IIIa is a group of the formula 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 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 is 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 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 of Q.