Template-fixed beta-hairpin peptidomimetics with CXCR4 antagonizing activity

摘要

Template-fixed β-hairpin peptidomimetics of the general formula (I);
wherein Z is a template-fixed chain of 12, 14 or 18 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid), are Gly, NMeGly, Pro or Pip, or of certain types which, as the remaining symbols in the above formula, are defined in the description and the claims, and salts thereof, have CXCR4 antagonizing properties These β-hairpin peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

主权项

1. A compound of the general formulais a dipeptide residue made up of two different amino acid building blocks, the dipeptide being DPro-LPro; andZ is a chain made up of 12 α-amino acid residues, in which
the P1 residue is the residue of Tyr; the P2 residue is the residue of Arg or Gly; the P3 residue is the residue of Cit; the P4 residue is the residue of Val, Phe, Cys, Gly, Ile, Thr or Gln; the P5 residue is the residue of Arg; the P6 residue is the residue of DArg or Arg; the P7 residue is the residue of Arg; the P8 residue is the residue of 2-Nal or Trp; the P9 residue is the residue of Phe, Val, Cys, Gly, Ile, Thr or Gln; the P10 residue is the residue of Tyr; the P11 residue is the residue of Cit or Gly; the P12 residue is the residue of Lys;when P4 and P9 are both cysteine, a disulfide bridge is present between the two side chains thereof; or an enantiomer of said compound,or a pharmaceutically acceptable salt of said compound.