Synthesis and structure–activity studies of novel homomorpholine oxazolidinone antibacterial agents

A novel series of oxazolidinones were synthesized in which the morpholine C-ring of linezolid was replaced with homomorpholine. In addition to investigating the effect of a homomorpholine C-ring on antibacterial activity, the effect of des-, mono-, di-, and tri-fluoro substitution on the phenyl B-ring was investigated as well. Various C-5 functional groups were also examined, including acetamides and triazoles and carboxamides.     

Synthesis and in vitro activity of new methylenepiperidinyl and methylenepyrrolidinyl oxazolidinone antibacterial agents

We have prepared and evaluated the antibacterial activities of a series of substituted methylenepiperidinyl and methylenepyrrolidinyl oxazolidinones against several gram-positive strains including the resistant strains of Staphyloccus and Enterococcus, such as MRSA, CRSA, MSSA and VRE. Some of them showed comparable or superior in vitro activities (MIC) to vancomycin.     

Synthesis and in vitro activity of novel 1,2,4-triazolo[4,3-a]pyrimidine oxazolidinone antibacterial agents

The synthesis and antibacterial activity of 3-(4-([1,2,4]triazolo[4,3-a]pyrimidin-3-yl)phenyl)oxazolidin-2-ones is reported. Thiocarbonyl derivatives were found to be potent inhibitors of Gram-positive pathogens and compound 4l was two to fourfold more potent than Linezolid.     

Synthesis and in vitro activity of new oxazolidinone antibacterial agents having substituted isoxazoles.

Two series of oxazolidinone derivatives having substituted isoxazoles were synthesized and tested for antibacterial activities against several Gram-positive strains including the resistant strains of Staphylococcus and Enterococcus, such as MRSA, CRSA, MSSA and VRE. Some of them showed in vitro activities (MIC) comparable or superior to the reference compound vancomycin.     

Synthesis and structure-activity studies of novel benzocycloheptanone oxazolidinone antibacterial agents

We describe a novel class of benzocycloheptanone derived oxazolidinone antibacterial agents. The synthesis and antibacterial activities with structure variation is discussed.     

Synthesis and in vitro activity of novel 1,2,4-triazolo[4,3-a]pyrimidine oxazolidinone antibacterial agents. Part II

The synthesis and antibacterial activity of 1,2,4-triazolo[4,3-a]pyrimidine oxazolidinones is reported. Compound 3e with a 2,4-disubstituted thiophene ring was found to be a potent inhibitor of Gram-positive pathogens and was 4-16-fold more potent than Linezolid.     

Synthesis of novel oxazolidinone antimicrobial agents

The oxazolidinone class of antimicrobials represents a promising advance in the fight against resistant Gram-positive bacterial infections. Four novel oxazolidinone antimicrobial compounds, each containing a benzodioxin ring system, have been prepared. The general synthesis of each compound begins with the construction of a benzodioxin ring system containing a nitro substituent that ultimately becomes the nitrogen of the oxazolidinone ring. Three of the compounds utilize high yielding 'click chemistry' in their final step. The antimicrobial activities of the new oxazolidinones have been measured and the MIC against Staphylococcus aureus for one of the antimicrobials was determined to be 2-3 microg/mL, which is comparable to the well-known oxazolidinone, linezolid.     

Recent developments in the identification of novel oxazolidinone antibacterial agents

The oxazolidinones are a promising new class of synthetic antibacterial agents. Here, we review recent efforts directed at the discovery of new antibacterial compounds of this class. New structures and structure-activity relationships (SAR) are discussed in the context of earlier work in the field. Key issues of potency, spectrum, selectivity, in vivo efficacy, and pharmacokinetic profile of the new analogs are addressed.     

Synthesis and antibacterial activity of novel (un)substituted benzotriazolyl oxazolidinone derivatives

A series of novel (un)substituted benzotriazolyl oxazolidinone derivatives has been synthesized and tested for in vitro antibacterial activities by MIC determination against a panel of susceptible and resistant Gram-positive and Gram-negative microorganisms, some of which are resistant to methicillin and vancomycin. Compounds 20, 21, 24, 29 and 30 from this series were found to be equipotent or more potent than linezolid in vitro.     

Synthesis and antibacterial activity of oxazolidinone containing sulphonyl group

A series of oxazolidinone derivatives carrying sulphonyl group was synthesized and their antibacterial activity was evaluated in vitro. Many of such compounds demonstrated potent antibacterial activity. The activity of a novel compound (YC-20) was 2-4-fold more potent than that of linezolid.     

Synthesis, SAR, and antibacterial activity of novel oxazolidinone analogues possessing urea functionality

The syntheses of a number of novel oxazolidinone analogues possessing an urea functionality are reported. While the urea derivatives possessing aliphatic and aromatic groups were prepared by the more conventional isocyanate method, the derivatives possessing heterocyclic rings were synthesized by a relatively uncommon but otherwise efficient carbamate chemistry. Though the SAR resulted in novel compounds possessing in vitro activity equivalent to Linezolid, the compounds possess a range of substituents that are amenable for altering physicochemical properties of the resultant drug. The antibacterial activity was found to be not sensitive to the functional groups attached to the urea site regardless of the size and electronic characteristics. Based on in vivo results, one molecule has been identified as a candidate and additional work such as salt selection, scale-up, etc., are currently underway to take the molecule further through development.     

Synthesis and in vitro study of novel Mannich bases as antibacterial agents

A series of novel Mannich bases derived from 5-chloro-2-methoxybenzamide and sulfonamides/amines have been synthesised and the antibacterial activities were evaluated against various Gram positive and Gram negative strains of bacteria. Some of the synthesized compounds showed superior in vitro activities as compared to their parent sulfonamides.     

Synthesis and antibacterial activity of some aryloxy/thioaryloxy oxazolidinone derivatives

A series of aryloxy/thioaryloxy oxazolidinone derivatives has been synthesized and tested for in vitro antibacterial activity by MIC determination against a panel of susceptible and resistant Gram-positive and Gram-negative microorganisms, some of which are resistant to methicillin and vancomycin. Compounds 12a, 12b, 14a, and 14b from this series were found to be equipotent or more potent than linezolid in vitro.     

Synthesis and in vitro antibacterial activity of novel methylamino piperidinyl oxazolidinones

Design and synthesis of a few novel methylamino piperidinyl substituted oxazolidinones are reported. Their antibacterial activities have been evaluated in a MIC assay against broader panel of both susceptible and resistant Gram-positive strains. (S)-N-{3-[3-Fluoro-4-(methyl-{1-[3-(5-nitrofuran-2-yl)-acryloyl]-piperidin-4-yl}-amino)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 4i has shown comparable antibacterial activity to linezolid and eperezolid in the MIC assay, additionally compound 4i showed good antibacterial activity with an in vitro MIC value of 2-4 microg/mL against linezolid resistant Staphylococcus aureus (linezolid 16 microg/mL).     

Synthesis and antibacterial evaluation of novel oxazolidinone derivatives containing a piperidinyl moiety

In this article, a series of novel oxazolidinone derivatives containing a piperidinyl moiety was designed and synthesized. Their antibacterial activities were measured against S. aureus, MRSA, MSSA, LREF and VRE by MIC assay. Most of them exhibited potent activity against Gram-positive pathogens comparable to linezolid. Among them, compound 9h exhibited comparable activity with linezolid against human MAO-A for safety evaluation and showed moderate metabolism in human liver microsome. The most promising compound 9h, which showed remarkable antibacterial activity against S. aureus, MRSA, MSSA, LREF and VRE pathogens with MIC value of 0.25–1 μg/mL, was an interesting candidate for further investigation.     

In vitro activity of linezolid and eperezolid, two novel oxazolidinone antimicrobial agents, against anaerobic bacteria

Linezolid (formerly U-100766) and eperezolid (formerly U-100592) are novel oxazolidinone antimicrobial agents that are active against multi-drug-resistant staphylococci, streptococci, enterococci, corynebacteria, and mycobacteria. Preliminary studies also demonstrated that the compounds inhibited some test strains of anaerobic bacteria. Therefore, we extended the in vitro evaluation of these agents to include a total of 54 different anaerobic species. Minimal inhibitory concentration (MIC) values were determined using a standard agar dilution method for 143 anaerobic bacterial isolates. Eperezolid and linezolid demonstrated potent activity against the anaerobic Gram-positive organisms with most MIC values in the range of 0.25-4 microg/mL. Viridans streptococci demonstrated MICs of 1-2 microg/mL; Peptostreptococcus species and Propionibacterium species were inhibited by 相似文献   

Recent development of potent analogues of oxazolidinone antibacterial agents

The oxazolidinones are a new and potent class of antimicrobial agents with activity mainly against Gram-positive strains. The commercial success of linezolid, the only FDA-approved oxazolidinone, has prompted many pharmaceutical companies to devote resources to this area of investigation. Until now, four types of chemical modifications of linezolid and oxazolidinone-type antibacterial agents, including modification on each of the A-(oxazolidinone), B-(phenyl), and C-(morpholine) rings as well as the C-5 side chain of the A-ring substructure, have been described. Division into sections according to side chain modification or the type of ring will be used throughout this review, although the process of synthesis usually involves the simultaneous modification of several elements of the linezolid substructure; therefore, assignment into the appropriate section depends on the structure–activity relationships (SAR) studies.This review makes an attempt to summarise the work carried out in the period from 2006 until mid-2012.     

Synthesis and in vitro antibacterial activity of novel fluoroquinolone derivatives containing substituted piperidines

We report herein the synthesis of novel 7-(4-alkoxyimino-3-aminomethyl-3-methylpiperidin-1-yl) fluoroquinolone derivatives. The antibacterial activity of the newly synthesized compounds was evaluated and correlated with their physicochemical properties. Results reveal that all of the target compounds have good potency in inhibiting the growth of Staphylococcus aureus and Staphylococcus epidermidis including MRSE (MIC: 0.125–4 μg/mL). Compounds 12, 13 are more potent than or comparable to levofloxacin against MRSA, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, and Shigella sonnei. Compound 17 is more active than or comparable to levofloxacin against S. aureus including MRSA, S. epidermidis and S. pyogenes.     

Synthesis and antibacterial activity of aminosugar-functionalized intercalating agents

A series of previously reported amino sugar-functionalized intercalating agents, 3-14, were evaluated in two antibacterial assays (paper disk diffusion and 96-well microdilution) against Bacillus atrophaeus, ATCC 9372 and Escherichia coli, ATCC 47076. Although none of the compounds were active against this E. coli strain, several showed activity against B. atrophaeus. In anticipation of the need for larger amounts of these compounds for future structure-activity relationship studies, improved routes to 11-14 were developed.     

Synthesis and in vitro study of novel 7-O-acyl derivatives of Oroxylin A as antibacterial agents

A series of Oroxylin A derivatives, prepared by alkylation and condensation, were fully characterized by spectroscopic methods. All the derivatives were screened for antibacterial activity against a panel of susceptible and resistant Gram-positive and Gram-negative organisms. It was observed that acylation of 7-OH group in Oroxylin A significantly enhanced the activity as compared to their parent compound (Oroxylin A).