PD-140248 (Parke-Davis & Co).
PD-140248 is an isomerase inhibitor and topoisomerase II inhibitor under development by Parke-Davis and Co as a potential treatment for bacterial infection. Although no details of active development have been published in the scientific literature since 1996, in September 1999, the company confirmed that PD-140248 is still in active development [338530]. The compound is one of two new pyrrolidinyl naphthyridines (the other compound being PD-131628) with a broad spectrum of antibacterial activity, including activity against quinolone-resistant bacteria. PD-140248 demonstrates strong in vitro activity, particularly against Gram-positive bacteria, such as quinolone-susceptible Staphylococcus aureus (S aureus), Staphylococcus epidermidis (S epidermidis), Staphylococcus haemolyticus (S haemolyticus), methicillin- and ciprofloxacin-resistant S aureus, Streptococcus species, Streptococcus pneumoniae (S pneumoniae) and Enterococcus faecalis (E faecalis). An MIC90 value of 0.015 microg/ml was obtained against Haemophilus influenzae (H influenzae) and Moraxella catarrhalis [160129]. The (3R,1S) enantiomer, PD-140248, demonstrated a 1- to 10-fold enhanced activity against Gram-positive and Gram-negative organisms in vitro and in vivo compared to its stereoisomers, and has thus been targeted for further preclinical studies [133377].
Steiert
M
M
Institute for Medical Microbiology and Virology, University Hospital Düsseldorf, Germany.
Schmitz
F J
FJ