Novel conformationally restricted analogues of agomelatine were synthesized and pharmacologically evaluated at MT₁ and MT₂ melatoninergic receptors. Replacement of the N-acetyl side chain of agomelatine by oxathiadiazole-2-oxide (compound 3), oxadiazole-5(4H)-one (compound 4), tetrazole (compound 5), oxazolidinone (compound 7a), pyrrolidinone (compound 7b), imidazolidinedione (compound 12), thi...

The oxazolidinone antimicrobial, linezolid, has been approved for the treatment of infections caused by various gram-positive bacteria, including vancomycin-resistant enterococci (VRE). This is the first report on isolation of a linezolid resistant, vancomycin-resistant Enterococcus faecium (LRVREF) strain in Poland, from a Haematological Unit patient in the Clinical Hospital in Gdańsk. PCR-RFL...

Seven-membered heterocyclic [1,2,5]triazepane and [1,2,5]oxadiazepane derivatives were synthesized as candidate structures for application in drug discovery in place of conventional piperazine or morpholine moieties, offering multiple sites for modification with functional groups. We first synthesized the N-protected heterocycles, and then confirmed their utility by synthesizing analogues of th...

The emergence of resistance in gram-positive bacteria has necessitated a search for new antimicrobial agents. Linezolid is an oxazolidinone, a new class of antibacterial agents with enhanced activity against pathogens. We compared the activity of linezolid to those of other antimicrobial agents against 3,945 clinical isolates. Linezolid demonstrated potent activity against all isolates tested. ...

Certain Gram-positive bacteria, including meticillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and quinolone-resistant Streptococcus pneumoniae have achieved the status of "superbugs", in that there are few or no antibiotics available for therapy against these pathogens. Only a few classes of novel antibiotics have been introduced in the past 40 years, and all since 199...

A diastereoselective and modular approach to the synthesis of the 3-hydroxymethyl-2,3,5,6,7,7a-hexahydro-1H-pyrrolizine-1,2,7-triol structure, characteristic of several natural pyrrolizidine natural products, has been developed. This approach culminated in the synthesis of (-)-7-epiaustraline and (+)-1,7-diepiaustraline. The oxazolidinone group has been found to be a useful protecting group in ...

The in vitro activity of AZD2563, a novel oxazolidinone, was assessed against 595 Gram-positive cocci, comprising recent surveillance isolates and a collection of resistant (including multiresistant), epidemiologically diverse isolates. The MICs of AZD2563 for staphylococci, pneumococci and enterococci had narrow ranges, 0.25-2 mg/L, with modal MICs of 1 mg/L for staphylococci and pneumococci, ...

An azide-functionalised analogue of the oxazolidinone antibiotic linezolid was synthesised and shown to retain antimicrobial activity. Using facile 'click' chemistry, this versatile intermediate can be further functionalised to explore antimicrobial structure-activity relationships or conjugated to fluorophores to generate fluorescent probes. Such probes can report bacteria and their location i...

The activity of ranbezolid (RBX 7644), a new oxazolidinone, against 306 anaerobes was compared with those of 11 other agents. The MICs at which 50% of the isolates tested are inhibited and those at which 90% of the isolates tested are inhibited (in micrograms per milliliter) were as follows: ranbezolid, 0.03 and 0.5; linezolid, 2 and 4; vancomycin, >16 and >16; teicoplanin, 1 and >16; quinupris...

Asymmetric epoxidation of various styrenes using carbocyclic oxazolidinone-containing ketone 3 has been investigated. High enantioselectivity (89-93% enantiomeric excess) has been attained for this challenging class of alkenes. Mechanistic studies show that substituents on the ketone catalyst can have electronic influences on secondary orbital interactions, which affects the competition between...