Peptide analogues containing a 7-membered lactam ring
AssigneeZeneca Limited
InventorsRichard William Arthur Luke, Ronald Cotton
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Abstract
The invention concerns pharmaceutically useful peptide derivatives of the formula (I), P—R1—R2—R3—R4, in which P, R1, R2, R3, and R4 have the various meanings defined herein, and their pharmaceutically acceptable salts, and pharmaceutical compositions containing them. The novel peptide derivatives are of value in treating MHC class II dependent T-cell mediated autoimmune or inflammatory diseases, such as rheumatoid arthritis. The invention further concerns processes for the manufacture of the novel peptide derivatives and the use of the compounds in medical treatment.
Claims12
A peptide compound of the formula I, P—R1—R2—R3—R4, or a pharmaceutically acceptable salt thereof, wherein
- P is a hydrophobic residue;
- R1 is a sequence of 5 L-amino acids and R3 is a single L-amino acid;
- or
- R1 is a sequence of 3 L-amino acids and R3 is a sequence of 3 L-amino acids;
- R2 is a group of formula II
- in which Ra is independently selected from hydrogen and (1-4C)alkyl;
- 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 —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
- 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-substitutent 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.
Dependencies are inferred from the claim text.