Abstract:
:SCH 56592 is a novel triazole antifungal agent that is active both orally and intravenously in animal models of infection. This compound is in Phase II-III clinical trials for the treatment of systemic fungal infections. SCH 56592 is a single enantiomer with four stereogenic centers; therefore, it was necessary to evaluate the possible chiral inversion of this drug candidate in animals and humans. Thus, chiral high-performance liquid chromatographic (HPLC) methods have been developed to separate SCH 56592 from its diastereomers and to evaluate its chiral inversion in rats, dogs, cynomolgus monkeys, and humans. Chiral HPLC analysis involved the use of a Chiralcel OD column set at 39 degrees C with a mobile phase of hexane-ethanol-diethylamine and a fluorescence detector set at an excitation wavelength of 270 nm and an emission wavelength of 390 nm. Plasma or serum samples were subjected to solid phase extraction on a C(2) cartridge followed by HPLC analysis. The method was sensitive with a limit of quantitation of 0.1 microg/ml in dog serum. The linearity was satisfactory, as shown by correlations of >0.997 and by visual examination of the calibration curves. The precision and accuracy were satisfactory, as indicated by coefficients of variation (CV) ranging from 1.1 to 12.1% and bias values ranging from -11.0 to 9.0%. Chiral HPLC analysis indicated that SCH 56592 was not subjected to chiral inversion in rats, dogs, cynomolgus monkeys, and humans.
journal_name
Chiralityjournal_title
Chiralityauthors
Kim H,Lin CC,Laughlin M,Lovey R,Saksena A,Heimark L,Nomeir AAdoi
10.1002/1520-636X(2000)12:7<590::AID-CHIR7>3.0.CO;subject
Has Abstractpub_date
2000-07-01 00:00:00pages
590-7issue
7eissn
0899-0042issn
1520-636Xpii
10.1002/1520-636X(2000)12:7<590::AID-CHIR7>3.0.CO;journal_volume
12pub_type
临床试验,杂志文章相关文献
CHIRALITY文献大全abstract::Although the organocatalytic direct asymmetric Michael reactions of carbonyl compounds to nitroalkenes have been investigated intensely, the Michael reaction of the thioether-based donors remains a rather undeveloped field. This work concerns the asymmetric Michael addition of aryl sulfanyl-propan-2-one to nitroalkene...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20689
更新日期:2010-07-01 00:00:00
abstract::About 30% of a chemically diverse set of compounds were found to separate on four polysaccharide chiral stationary phases using polar organic mobile phases. No structural features appeared to correlate to successful separations. Titrations between normal and polar organic mobile phases suggested that separation mechan...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20212
更新日期:2006-01-01 00:00:00
abstract::Vibrational circular dichroism (VCD) spectra of (+)-alpha-pinene solutions in carbon tetrachloride have been measured in the range of volume fractions 5-100% (v/v) in the mid-infrared region. The concentration dependence measured was statistically analyzed with the aim of obtaining a reliable correlation between the V...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/(SICI)1520-636X(2000)12:4<199::AID-CHIR6>3
更新日期:2000-05-01 00:00:00
abstract::Vibrational circular dichroism spectra (VCD) in the mid-IR region and electronic circular dichroism (ECD) spectra for three carnitine derivatives in the form of hydrochloride salts were recorded in deuterated methanol solutions. Density Functional Theory calculations help one to understand the significance of the obse...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.22532
更新日期:2015-12-01 00:00:00
abstract::Asymmetric molecular and supramolecular systems are characterized by: i. the circular dicroism in the angular distribution of valence photoelectrons emitted from randomly oriented chiral molecules by their interaction with circularly polarized VUV light; ii. the different stability and reactivity of diastereomeric agg...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20274
更新日期:2006-08-01 00:00:00
abstract::The hydrolysis and acyl migration of biosynthetic S-naproxen-beta-l-O-acyl glucuronide (I) and R-naproxen-beta-l-O-acyl glucuronide (II) was followed by HPLC. Nine first-order kinetic rate constants for the hydrolysis and acyl migration between the beta-l-O-acyl glucuronide, its alpha/beta-2, alpha/beta-3-, alpha/beta...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.10047
更新日期:2002-05-05 00:00:00
abstract::A new water soluble zinc-salophen complex with appended D-glucose moieties was synthesized and characterized. Its binding properties toward six aminoacids were investigated by UV-vis spectrophotometric titrations. Association constants showed to be unfavorably affected by increasing steric hindrance of the side chain....
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20614
更新日期:2009-01-01 00:00:00
abstract::In the presence of tridentate chiral ligand 4e, 99% e.e. value was obtained by asymmetric reduction of ethyl benzoylacetate with borane in toluene at 25 degrees C. Various ligands and reaction conditions were investigated to develop a reasonable mechanism that explains the experimental outcomes. ...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20344
更新日期:2007-02-01 00:00:00
abstract::Polymorphonuclear neutrophils (PMNs) are short-lived leukocytes that die by apoptosis. Although PMNs are crucial in the defense against infection, they have been implicated in the pathogenesis of tissue injury observed in inflammatory diseases. The induction or prevention of PMN apoptosis is currently discussed as a k...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20516
更新日期:2008-02-01 00:00:00
abstract::This work reports confirmation of the experimental assignment of the absolute-handedness chirality of single-walled carbon nanotubes (SWNTs). This was achieved by applying the scanning tunneling microscopy (STM) imaging technique to a supramolecular composite consisting of a metalized porphyrin derivative (nickel-5,15...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.23163
更新日期:2020-03-01 00:00:00
abstract::Chiral pesticides are now receiving more and more attention in the food-making process. This experiment studied the enantioselective behavior of diclofop-methyl (DM) and its main metabolite, diclofop (DC), during the soy sauce brewing process. Two kinds of commonly used strains, Aspergillus oryzae and Saccharomyces ro...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.22545
更新日期:2016-01-01 00:00:00
abstract::Novel chiral diisopropyl spiro bis(isoxazoline) ligands, anti-i-Pr-SPRIX and syn-i-Pr-SPRIX, were designed and synthesized. Their catalytic utility, X-ray crystallographic analyses, and complexation studies demonstrated the structural features of tetraisopropyl spiro bis(isoxazoline) ligand, i-Pr-SPRIX, which is a pro...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.22467
更新日期:2015-08-01 00:00:00
abstract::[3β,5β,7α,12α]-3-(4-t-Butylbenzoilamine)-7,12-dihydroxycholan-24-oic acid was synthesized and recrystallized from chlorobenzene and acetone. Orthorhombic P2(1)2(1)2(1) and monoclinic P2(1) crystals were obtained, respectively, and both crystals include solvent and water molecules with a 1:1:1 stoichiometry. In the sec...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.21020
更新日期:2011-11-01 00:00:00
abstract::Perfluorooctane sulfonate (PFOS) is one of the most frequently detected perfluoroalkyl substances in environmental and human samples. Previous studies have shown that nonracemic PFOS in biological samples can be used as a marker of PFOS exposure sources. In recent years, supercritical fluid chromatography (SFC) has em...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.23120
更新日期:2019-10-01 00:00:00
abstract::Doping nematic liquid crystals with nonracemic chiral compounds induces a twisted nematic (cholesteric) phase. The ability of solutes to twist the nematic phase may be related to the overall shape of the chiral dopant and consequently to its absolute configuration. The cholesteric induction is therefore a powerful too...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20482
更新日期:2008-05-15 00:00:00
abstract::Nine patients taking oral doses of 10 mg/12 h rac-pindolol as part of their treatment for hypertension in pregnancy were recruited for the study. Maternal and fetal gestational age ranged from 20-38 years and 28-41 weeks, respectively. Blood was collected from the umbilical cord vein and from the mother from zero to 1...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.10124
更新日期:2002-08-01 00:00:00
abstract::The direct asymmetric aldol reactions of equivalent molar amounts of aldehydes and ketones were carried out at -20 degrees C over alkaline Al(2)O(3) with 20 mol % of Pro-Trp as catalyst and 20 mol % of N-methylmorpholine or 1,4-diazabicyclo[2.2.2]octane as additive. After simple and environmentally friendly work-up, m...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20783
更新日期:2010-06-01 00:00:00
abstract::A three-dimensional molecularly imprinted overoxidized polypyrrole/MnO2 /carbon felt (MIOPPy/MnO2 /CF) composites were fabricated, which results in increased active area of the surface of the molecularly imprinted polymers film and greatly improved electrochemical chiral recognition effect for tryptophan isomers. The ...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.23126
更新日期:2019-11-01 00:00:00
abstract::An improved synthesis of the enantiomers of the new benzofurane-type antiarrhythmic compound 1 is described, which makes use of the enantiomerically pure mbe-lactol. Thus, acylation of the benzofurane 4 with acetic anhydride and subsequent bromination gave the bromoacetyl-derivative 6, which, after reduction with LiAl...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.530060417
更新日期:1994-01-01 00:00:00
abstract::A Micelle-enhanced ultrafiltration (MEUF) separation process was investigated that can potentially be used for large-scale enantioseparations. Copper(II)-amino acid derivatives dissolved in nonionic surfactant micelles were used as chiral selectors for the separation of dilute racemic amino acids solutions. For the al...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/1520-636X(2000)12:8<627::AID-CHIR5>3.0.CO;
更新日期:2000-08-01 00:00:00
abstract::Chiral discrimination in a racemic mixture of dipalmitoylphosphatidylcholine (DPPC) is induced by a new selector at the water-air interface: L-DPPC is segregated in the condensed phase of a Langmuir monolayer upon interactions with an enantiopure amphiphilic compound. ...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.22508
更新日期:2015-11-01 00:00:00
abstract::Efficient synthesis of several new atropisomeric amino alcohols having 1-phenyl-1H-pyrrole skeleton are reported. Steric arrangements of the products were confirmed by a single-crystal X-ray measurement. The consequences of the size of the N-substituents on enantioinduction were examined by employing the enantioselect...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.22415
更新日期:2015-03-01 00:00:00
abstract::Planar 2(5H)-furanones substituted at C4 with a chiral pyrrolidinyl group show CD spectra which are apparently due to the distortion of the C4-N1 bond of sp2 character from the plane defined by the 2(5H)-furanone ring atoms and/or due to the presence of substituents in the pyrrolidine ring. This is a new, previously n...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20059
更新日期:2004-08-01 00:00:00
abstract::Synthetic pyrethroid insecticides are chiral compounds with multiple asymmetric positions. In this study, isomers of four commonly used pyrethroids were separated at the enantiomeric level by enantioselective high-performance liquid chromatography (HPLC), and differences between enantiomers in aquatic toxicity were ch...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20122
更新日期:2005-01-01 00:00:00
abstract::This article describes a very useful extension of an unique column switching technique called "Simulated Moving Columns" (SMC) that was previously reported for chiral high performance liquid chromatography (HPLC) (Zhang and McConnell, Journal of Chromatography A 2004;1028:227-238). SMC uses two or three short chiral c...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.20409
更新日期:2007-09-01 00:00:00
abstract::In this work, we study the effect of different variables affecting elution profile distortion on the enantiomeric resolution eventually achievable when working with on-line coupled liquid chromatography to gas chromatography (LC-GC). Specifically, the proposed configuration combines achiral reversed-phase liquid chrom...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.23121
更新日期:2019-10-01 00:00:00
abstract::Experimental hyperlipidemia has shown to decrease cytochrome P450 3A4 and 2C11 expression and to increase liver concentrations and the plasma protein binding of halofantrine (HF) enantiomers. The present study examined the effect of hyperlipidemic (HL) serum on the metabolism of HF enantiomers by primary rat hepatocyt...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.22054
更新日期:2012-07-01 00:00:00
abstract::One of the most powerful techniques that are currently available to measure thermodynamic parameters such as enthalpy (ΔH), Gibbs free energy (ΔG), entropy changes (ΔS), and binding affinity in chemical reactions is isothermal titration calorimetry (ITC). Recent advances in instrumentation have facilitated the develop...
journal_title:Chirality
pub_type: 杂志文章,评审
doi:10.1002/chir.22842
更新日期:2018-05-01 00:00:00
abstract::Flurbiprofen is a kind of nonsteroidal anti-inflammatory drug, which has been widely used in clinic for treatment of rheumatoid arthritis and osteoarthritis. It has been reported that S-flurbiprofen shows good performance on clinic anti-inflammatory treatment, while R-enantiomer almost has no pharmacological activitie...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/chir.23071
更新日期:2019-06-01 00:00:00
abstract::Weinreb amide 3 was synthesized using isobutyl chloroformate, carbonyldiimidazole, or ethylcarbodiimide as the coupling agent in the reaction of Boc-phenylalanine with O,N-dimethylhydroxylamine hydrochloride. An optically active oil was isolated along with an optically inactive solid irrespective of the type of coupli...
journal_title:Chirality
pub_type: 杂志文章
doi:10.1002/(SICI)1520-636X(2000)12:1<2::AID-CHIR2>3.0
更新日期:2000-01-01 00:00:00