[Relationship between chemical structure and toxicologic-pharmacokinetic properties of new ampicillin derivatives]. / Beziehungen zwischen chemischer Struktur und toxikologisch-pharmakokinetischen Eigenschaften neuer Ampicillin-Derivate.

The toxicity and the bioavailability of new ampicillin derivatives with glyoxylic acid benzhydrazones as site chain depend on the hydrophobic properties of the site chain. Substituents with lower hydrophobicity (expressed by the hydrophobic substituent constant pi according to Hansch) show a lower toxicity (maximal tolerated doses) and also a lower bioavailability.

[New ampicillin derivatives with glyoxyloylbenzhydrazone side chains]. / Neue Ampicillinderivate mit Glyoxyloylbenzhydrazon-Seitenketten.

New ampicillin derivatives were synthesized from glyoxylic acid benzhydrazones by reaction with chloroformates via mixed anhydrides and ampicillin. These compounds were tested in an agar diffusion test against six different bacterial strains and also for their stability against beta-lactamases. Studies about structure-activity relationships have shown, that the activity against different bacterial strains is influenced in different manner by hydrophilic or hydrophobic and electronic properties of substituents.

[Synthesis and antibacterial activity of benzoylaminoacyl-penicillins and related compounds with and without acylated catechol substituents]. / Synthese und antibakterielle Wirksamkeit von Benzoylaminoacyl-Penicillinen und verwandten Verbindungen mit und ohne acylierte Catechol-Substituenten.

Synthesis and Antibacterial Activity of Benzoylaminoacyl Penicillins and Related Compounds with and without Acylated Catechol Substituents. Syntheses of benzoyl, cinnamoyl, and benzoylhydrazido glyoxyloyl aminoacyl penicillins with and without acylated catechol substituents by condensation of corresponding acids or acylchlorides with ampicillin or amoxycillin and also of a 6-a-methoxy-derivative and corresponding esters are reported. Acylated catechol substituents improve the antibacterial activity against Gram-negative bacteria, especially against Pseudomonas strains and Salmonella. MIC tests of bacterial mutants with higher outer membrane penetrability and of the corresponding wild typs show that the increase of antibacterial activity by catechol substituents is caused by improvement of the penetration through the bacterial outer membran. The affinity to penicillin binding proteins is not influenced by catechol substituents. Stability against beta-lactamases is partly higher than that of azlocillin.