Novel fluorobenzothiazole as a dual inhibitor of gyrase B and topoisomerase IV against Gram-positive pathogens.

The development of a novel inhibitor targeting gyrase B and topoisomerase IV offers an opportunity to combat multidrug resistance. We investigated the activity of RBx 10080758 against Gram-positive bacteria and . RBx 10080758 showed a potent 50% inhibitory concentration of 0.

Potential of the fluoroketolide RBx 14255 against Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae in an experimental murine meningitis model.

Background: RBx 14255 is a fluoroketolide in pre-clinical evaluation with potent activity against MDR Gram-positive pathogens.

Objectives: To investigate the efficacy of RBx 14255 against bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis or Haemophilus influenzae in an experimental murine meningitis model.

Methods: In vitro activity of RBx 14255 was evaluated against clinical isolates of S.

Synthesis and evaluation of thiomannosides, potent and orally active FimH inhibitors.

FimH is a type I fimbrial lectin located at the tip of type-1 pili of Gram-negative uropathogenic Escherichia coli (UPEC) guiding its ability to adhere and infect urothelial cells. Accordingly, blocking FimH with small molecule inhibitor is considered as a promising new therapeutic alternative to treat urinary tract infections caused by UPEC. Herein, we report that compounds having the S-glycosidic bond (thiomannosides) had improved metabolic stability and plasma exposures when dosed orally.

A novel ketolide, RBx 14255, with activity against multidrug-resistant Streptococcus pneumoniae.

We present here the novel ketolide RBx 14255, a semisynthetic macrolide derivative obtained by the derivatization of clarithromycin, for its in vitro and in vivo activities against sensitive and macrolide-resistant Streptococcus pneumoniae. RBx 14255 showed excellent in vitro activity against macrolide-resistant S. pneumoniae, including an in-house-generated telithromycin-resistant strain (S.

Synthesis and antibacterial activity of a novel series of acylides active against community acquired respiratory pathogens.

A novel series of acylides 4 were designed to overcome antibacterial resistance and evaluated for in vitro and in vivo activity. This series of acylides was designed from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate. These compounds showed significantly potent antibacterial activity against not only Gram-positive pathogens, including macrolide-lincosamide-streptogramin B (MLS(B))-resistant and efflux-resistant strains, but also Gram-negative pathogens such as Haemophilus influenzae.

Activity of a novel series of acylides active against community-acquired respiratory pathogens.

Resistance to macrolides and beta-lactams has increased sharply amongst key respiratory pathogens, leading to major concern. A novel series of acylides was designed to overcome this resistance and was evaluated for in vitro and in vivo activity. This series of acylides was designed starting from clarithromycin by changing the substitution on the desosamine nitrogen, followed by conversion to 3-O-acyl and 11,12-carbamate.

Novel biaryl oxazolidinones: in vitro and in vivo activities with pharmacokinetics in an animal model.

RBx 1000075 and RBx 1000276, the new investigational oxazolidinones, have an extended spectrum of in vitro activity against Gram-positive pathogens and showed minimum inhibitory concentrations (MICs) lower than comparator drugs. MIC for 90% of the organisms (MIC(90)) values of RBx 1000075, RBx 1000276 and linezolid against the isolates tested were, respectively: methicillin-sensitive Staphylococcus aureus, 0.25, 1 and 4 microg/mL; methicillin-resistant S.

Synthesis and antibacterial activity of potent heterocyclic oxazolidinones and the identification of RBx 8700.

Several potent oxazolidinone antibacterial agents were obtained by systematic modification of the linker between the five-membered heterocycle and the piperazinyl ring of RBx 7644 (Ranbezolid, 1) and its thienyl analogue 2, leading to the identification of an expanded spectrum compound RBx 8700 (6b).

Synthesis and antibacterial activity of novel oxazolidinones with methylene oxygen- and methylene sulfur-linked substituents at C5-position.

Novel oxazolidinone derivatives of the lead compound RBx 8700, containing methylene oxygen- and methylene sulfur-linked substituents at the C5-position, were synthesized. Antibacterial screening of these compounds against a panel of resistant and susceptible Gram-positive and fastidious Gram-negative bacteria gave compounds 2 and 4 as new antibacterial agents.

Characterisation of laboratory-generated vancomycin intermediate resistant Staphylococcus aureus strains.

Vancomycin has been the drug of choice for 30 years for the treatment of methicillin-resistant Staphylococcus aureus (MRSA). Emergence of decreased vancomycin susceptibility in MRSA strains presents a significant clinical problem with few therapeutic options. This study was performed to generate and characterise S.

Synthesis and SAR of novel oxazolidinones: discovery of ranbezolid.

Novel oxazolidinones were synthesized containing a number of substituted five-membered heterocycles attached to the 'piperazinyl-phenyl-oxazolidinone' core of eperezolid. Further, the piperazine ring of the core was replaced by other diamino-heterocycles. These modifications led to several compounds with potent activity against a spectrum of resistant and susceptible gram-positive organisms, along with the identification of ranbezolid (RBx 7644) as a clinical candidate.

In vitro activity of RBx 7644 (ranbezolid) on biofilm producing bacteria.

Biofilm associated infections are becoming more common. Treatment outcome of device related infections cannot be predicted by the results of a standard susceptibility test such as the MIC. Microorganisms involved in device related infections have a slow growth rate and adhere to surfaces.