Peptide derivatives containing a hydrophobic group, L-amino acid residues and modified L-amino acid residues

摘要

A peptide derivative having the formula (I) P-AA1-AA22-AA3-AA4-AA5-AA6-AA7-AA8-Q or a pharmaceutically acceptable salt thereof wherein: P is a hydrophobic residue; AA1 to AA8 are L-amino acid residues wherein 1 to 3 of AA1, AA4 and AA7 are residues of an L-amino acid of formula (II) HO-C(O)-CH(NH2)-(CH2)n-X-NR1R2 or AA1 to AA3 and AA6 to AA8 are L-amino acid residues wherein one or both of AA1 and AA7 have the formula II and AA4 together with AA5 form a group of formula III, IIIa, IV, IVa, V or Va or AA1 to AA5 and AA8 are L-amino acid residues in which one or both of AA1 and AA4 have the formula II and AA6 together with AA7 form a group of formula III, IIIa, IV, IVa, V or Va n is 1 to 4; X is -NHCO-, -CO- or -OC(O)-; R1 and R2 are independently -(CH2)a-CO-NR3R4, -(CH2)c-O-(CH2)d-CO-NR5R6 or -[(CH2)r-Og]-R7 with a, c, d, r and R3 to R7 being as defined in the specification; Ra , Rb and Rz are independently H or alkyl; A is oxygen or methylene and Q is OH, NH2, NRcRd or 1-piperazinyl, 4-methyl-1-piperazinyl, 4-(2-(2-hydroxyethoxy)ethyl)-1-piperazinyl, 4-amidino-1-piperazinyl, 1-piperidinyl or 4-(substituted)-1-piperidinyl wherein the substituent is carboxy, carbamoyl, N-(2-aminoethyl)-carbamoyl or N-(4-aminobutyl)carbamoyl or Q is a sequence of 1-6 amino acid residues or an amide thereof. A pharmaceutical composition containing a compound of formula I useful in the treatment of a MHC class II dependent T-cell mediated autoimmune or inflammatory disease is claimed.