Template-fixed peptidomimetics with antimicrobial activity

摘要

Template-fixed β-hairpin peptidomimetics of the general formula;
wherein Z is a template-fixed chain of 12 α-amino acid residues which, depending on their positions in the chain (counted starting from the N-terminal amino acid) are Gly, or Pro, 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 the property to selectively inhibit the growth of or to kill microorganisms such as Pseudomonas aeruginosa. They can be used as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials, or as medicaments to treat or prevent infections.
;These β-hairpin peptidomimetics can be manufactured by processes which are based on a mixed solid- and solution phase synthetic strategy.

主权项

1. A method of treating a disease or infection caused by Pseudomonas aeruginosa comprising administering to a subject in need thereof an effective amount of a compound represented by formula (I): is DPro-LPro or LPro-DPro and Z is a chain of 12 α-amino acid residues, wherein the positions of the amino acid residues in the chain are counted starting from the N-terminal amino acid, wherein the amino acid residues are, in positions P1 to P12 of the chain:
P1: Ala, Cit, Thr, Thr, Asp, or Glu;P2: Trp, or Tyr;P3: Ile, Val, Nle, Chg, or Cha;P4: Dab, Lys, or Gln;P5: Lys, Dab, or Orn;P6: Dab, DDab, or Lys;P7: His, Lys, Gln, or Dab;P8: Tyr, Trp, or Ser;P9 Dab or Lys;P10: Dab or Lys;P11: Ala, Abu, Thr, Gly, Pro, Hse, Ile, Nva, DAla, DVal, Aib, Nle, Chg, Cha, Gln, Asp, Glu, Cpa, t-BuG, Leu, Val, or Asn; andP12: Dab, Lys, Gln, or Ser, or a pharmaceutically acceptable salt or enantiomer thereof.