Novel Proteasome Modulators

A molecule of general formula (I), and the pharmaceutically acceptable salts thereof:

• (X0)x0—(X1)x1—(X2)x2—X3—(X4)x4—X5—X6—(X7)x7—(X8)x8—(X9)x9 (I)
• in which
• x0, x1, x2, x4, x7, xhd 8 and x9 each represent, independently, an integer equal to 0 or to 1;
• X0 represents a group chosen from those corresponding to formula (II):
• in which Y represents a saturated or unsaturated, linear, branched or cyclic C1-C24 alkyl group, n represents an integer chosen from 0 and 1;
• X1 and X3 each represent a natural or synthetic amino acid in the L or D configuration, each comprising at least one hydroxyl function on its side chain;
• X2 represents a natural or synthetic amino acid in the L or D configuration chosen from those comprising an alkyl side chain;
• X4 represents a natural or synthetic amino acid in the L or D configuration which can be chosen from those comprising an aromatic side chain;
• X5 represents an amino acid in the L or D configuration chosen from lysine, arginine, histidine, aspartic acid, asparagine, glutamic acid and glutamine;
• X6 represents an amino acid in the L or D configuration which can be chosen from tyrosine, phenylalanine, leucine, isoleucine, alanine, para-benzoylphenylalanine and lysine;
• X7 represents an amino acid in the L or D configuration which can be chosen from glycine, alanine, leucine, valine, asparagine and arginine;
• X8 represents an amino acid in the L or D configuration which can be chosen from proline, valine, isoleucine and aspartic acid;
• X9 represents an amino acid in the L or D configuration which can be chosen from serine, alanine, lysine, arginine and tryptophan;
• the bond between two successive amino acids Xi—Xi+1, denoted qi−i+1, i=1, . . . 8, can be a peptide bond
• or a pseudopeptide bond chosen from:
• CO—O, CO—S, CO—CH2, CO—N(Me), NH—CO, CH═CH, CH2—CH2, CH2—S, CH2—O, CS—NH, CH2—NH, CO—CH2—NH, CO—NH—NH, CO—NH—N═ and CO—N(NH2);
• the amino acids stated above Xi, i=1, . . . 9, being capable of comprising a modification of their α-carbon, denoted Ci, i=1, . . . 9, and bearing the side chain R of the amino acid, which modification consisting of the replacement of:
• with a group chosen from:
• the groups R and CH—R1 representing the side chain of the amino acid and R2 representing a C1-C6 alkyl group;
• R-R2 can constitute a ring,
• the pseudopeptides of the invention also corresponding to the following conditions:
• x0 is equal to 1 or
• one of the bonds qi−i+1, i=1, . . . 8, is a pseudopeptide bond or
• one of the Ci, i=1, . . . 9, comprises one of the modifications stated above.