Oxazolidinones

Background.—It has been suggested that triptans achieving higher central nervous system (CNS) levels should have an advantage in efficacy, if central actions are important.Objective.—Our aim was to correlate the efficacy and tolerability results of triptans with their lipophilicity.Methods.—Data for response and pain free at 2 hours, recurrence, adverse events (AE), CNS AE, and chest symptoms taken from Ferrari et al's meta-analysis publications for the recommended doses of oral triptans were correlated with their lipophilicity coefficients (logDpH7.4 =−2.1 almotriptan < −1.5 sumatriptan < −1.0 zolmitriptan < −0.7 rizatriptan < −0.2 naratriptan < 0.5 eletriptan).Results.—We found no significant correlation between lipophilicity coefficients and any of the analyzed parameters. There was, however, some correlation between lipophilicity and CNS AE (P= .09, r= 0.74) and, to a lesser degree, with a reduction in recurrence rate (r=−0.36). The r values for response and pain free with placebo correction ranged from 0.04 to 0.34, suggesting almost no correlation between lipophilicity and efficacy variables.Conclusions.—According to this analysis, a higher lipophilicity does not seem crucial to improve triptan efficacy. This physico-chemical property, however, correlates with higher CNS AE and, possibly, lower recurrence rates.

A chiral liquid chromatographic method for enantiomeric resolution of β-amino-β-(3-methoxyphenyl) propionic acid was developed and validated. The “hybrid” π-electron donor–acceptor based stationary phase (R,R) Whelk-01 was found to be enantiomerically selective for (R) and (S) enantiomers of β-amino-β-(3-methoxyphenyl) propionic acid with a resolution greater than 2.0. The effects of isopropyl alcohol and ethanol on enantioselectivity and resolution of enantiomers were evaluated. Calibration curves were linear over the range of 0.10–1.00, with a regression coefficient (r) of 0.999. The limit of detection (LOD) and limit of quantification (LOQ) were 300 and 1,000 ng mL−1 respectively for 10 μL injection volume. The percentage RSD of the peak area of six replicate injections of (S) enantiomer at LOQ concentration was 2.8. The percentage recovery of (S) enantiomer from (R) enantiomer samples ranged from 92 to 102. The test solution was observed to be stable up to 24 h after the preparation. The developed normal phase chiral LC method can be used for the enantiomeric purity evaluation of R-β-amino-β-(3-methoxyphenyl) propionic acid.

Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by the simultaneous measurement of linezolid levels in serum and cerebrospinal fluid.

Novel 5-phenyl-1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2,4(3H)-dithiones, 5-phenyl-3,5-dihydro-4H-chromeno[2,3-d]pyrimidin-4-ones, 7-phenyl-7,9-dihydro-8H pyrimido[5′,4′:5,6]pyrano[3,2-h]quinolin-8-ones, and 4-amino-5-phenyl-1,5-dihydro-2H-chromeno[2,3-d]pyrimidine-2-thiones were synthesized form 2-amino-4-phenyl-4H-chromene-3-carbonitrile. The newly synthesized compounds were characterized by IR, 1H-NMR, 13C-NMR, Mass spectra, and Elemental analysis. The compounds were evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H 37 Rv and antibacterial activity against Staphylococcus Aureus [ATCC-25923] and Streptococcus pyogenes [MTCC-443] as Gram-positive, Escherichia coli [ATCC-25922], and Pseudomonas aeruginosa [MTCC-441] as Gram-negative bacterial strains and antifungal activity against Aspergillus niger [MTCC-282]. Some of these derivatives exhibited pronounced antitubercular and antimicrobial activities.