| 摘要 |
Beta-hairpin peptidomimetics of the general formula (I), cyclo[P1-p2-p3-p4-p5-p6-p7-p8p9-p10-p11-p12-T1-T2], and pharmaceutically acceptable salts thereof, with P1 to P12, T1 and T2 being elements as defined in the description and the claims, have Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiella pneumoniae and/or Acinetobacter baumannii and/or Escherichia coli. They can be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These 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 formula (I),
cyclo[P1-P2-P3-P4-P5-P6-P7-P8-P9-P10-P11-P12-T1-T2] (I)wherein the single elements T or P are connected in either direction from the carbonyl (C═O) point of attachment to the nitrogen (N) of the next element and wherein
T1 is a naturally or non-naturally occurring D α-amino acid containing an optionally substituted side-chain which forms a five-membered heterocycle or a bicyclic system comprising the α-carbon and the α-amino atom; T2 is a naturally or non-naturally occurring L α-amino acid containing an optionally substituted side-chain which forms a five- or six-membered heterocycle or a bicyclic system comprising the α-carbon and the α-amino atom; P1 and P12 are independently
a naturally or non-naturally occurring L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain; P2 is a naturally or non-naturally occurring aliphatic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain; or
a naturally or non-naturally occurring L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one urea function, amide function, ester function, sulfone function or ether function; ora naturally or non-naturally occurring basic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one amino function; ora naturally or non-naturally occurring alcoholic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain; orGly; P3 and P10 are independently
a naturally or non-naturally occurring aliphatic or aromatic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain; P4 and P9 are independently
a naturally or non-naturally occurring basic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one amino function; ora naturally or non-naturally occurring alcoholic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain; P5 is a naturally or non-naturally occurring basic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one amino function; P6 is a naturally or non-naturally occurring basic L or D α-amino acid or cyclic α,α-disubstituted α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one amino function; P7 is a naturally or non-naturally occurring basic L or D α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one amino function; P8 is a naturally or non-naturally occurring aromatic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain; P11 is a naturally or non-naturally occurring L or D α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain;or a tautomer or rotamer thereof, or a salt, or a hydrate or solvate thereof;with the proviso that
if P2 is a naturally or non-naturally occurring basic L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one amino function; or a naturally or non-naturally occurring L α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one urea function, amide function, ester function, sulfon function or ether function; then P11 is a naturally or non-naturally occurring aliphatic L or D α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain;
or a naturally or non-naturally occurring alcoholic L or D α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain;or a naturally or non-naturally occurring L or D α-amino acid containing in total 1 to 25 carbon- and/or heteroatoms in a single side-chain comprising at least one ester function, sulfon function, ether function, acid function or amide function. |
