摘要:

AbstractA molecular mechanics investigation of R‐ vs. S‐phenylethanol, R‐ vs. S‐mandelic acid, R‐ vs. S‐flurbiprofen, and R‐ vs. S‐fenoprofen in their cyclodextrin crystal environments was undertaken. It was found that the dominant force responsible for guesthost complexation is the short‐range London force; the enantiodiscriminating forces tend to be very small and are generally, but not always, dominated by long‐range electrostatic contributions. Derivatized cyclodextrins are generally more enantiodiscriminating than native cyclodextrins, perhaps due to exterior rather than interior guest‐host binding.

ISSN:0899-0042    

DOI:10.1002/chir.530050202

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractIt is shown, using in vitro measurements of beat frequency of rat tracheal cilia, that (+)‐(1S, 2R, 5S)‐menthol and (−)−(1R, 2S, 5R)−menthol have equipotent ciliotoxicities despite the fact that inhalation of menthol vapours from the crystals of the pure enantiomers show clearly that the (−)−(1R, 2S, 5R)‐menthol produces a more potent cooling sensation. Differential scanning calorimetry demonstrates the formation of a racemic compound when equimolar amounts of the two enantiomers are admixed. © 1993

ISSN:0899-0042    

DOI:10.1002/chir.530050203

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe pharmacokinetics of the enantiomers of the non‐steroidal anti‐inflammatory drug pirprofen were studied in male Sprague‐Dawley rats after oral and intravenous (iv) doses of the racemate. No significant differences were detected between the enantiomers after oral or iv dosing in t½, Vd, or ∑Xu. However, the R:S area under the plasma concentration (AUC) ratio after oral doses (0.92 ± 0.13) was slightly but significantly lower than after matching iv doses (1.05 ± 0.036). The absolute bioavailability of the active S‐enantiomer (78.5%) after oral doses was higher than the inactive R‐enantiomer (69.3%). The plasma protein binding of both enantiomers was saturable over a fivefold range of plasma concentrations. At higher plasma concentrations, the S‐enantiomer was less bound than the R‐enantiomer. In an in vitro experiment using everted rat jejunum, no chiral inversion was discernible. The dependency of the AUC ratio of the enantiomers on the route of administration may be due to stereoselective first‐pass metabolism. ©

ISSN:0899-0042    

DOI:10.1002/chir.530050204

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractA sequential achiral‐chiral high‐performance liquid chromatographic system has been developed for the quantitation in urine of the enantiomers of hydroxychloroquine (HCQ), and of its 3 major metabolites, desethylhydroxychloroquine (DHCQ), desethylchloroquine (DCQ), and bisdesethylchloroquine (BDCQ). HCQ and its metabolites were separated and quantified on a cyano‐bonded phase, and the enantiomeric ratios were determined using a Chiral‐AGP chiral stationary phase. The assay validation and application of this method to a preliminary study in a human volunteer are presented. In this subject, the initial 0‐4 h urine contained the 2 HCQ enantiomers in a ratio of (+)‐HCQ:(−)‐HCQ of 3:2; by the 2,064 h of the study, this ratio had reversed to (+)‐HCQ:(−)‐HCQ of 3:7.

ISSN:0899-0042    

DOI:10.1002/chir.530050205

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractSpecific ligand markers for the various binding sites of human serum albumin (HSA) have been described in the literature. Some of these markers (medium chain fatty acids, warfarin, digoxin, and bilirubin) were used as mobile phase modifiers. Using a high performance liquid chromatographic (HPLC) column containing HSA as stationary phase, their influence was investigated on the separation in this phase of the enantiomers of three benzodiazepines (temazepam, oxazepam, and lorazepam). Displacement effects were observed with medium chain fatty acids. This influence was proportional to the chain length and to the concentration of acid. Allosteric cooperative effects were noted with digoxin for the three benzodiazepines. Both displacement and cooperative effects were observed with warfarin. Stereoselectivity was decreased for temazepam and oxazepam and increased for lorazepam. © 1993 Wiley‐Liss, I

ISSN:0899-0042    

DOI:10.1002/chir.530050206

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractBecause of the constantly increasing demand for optically pure drugs it is of great importance to elucidate factors affecting stereochemistry, in order to provide a stable formulation with a high chiral quality of the desired isomer. Therefore, the effects of cyclodextrins (CyDs) and their alkylated and hydroxyalkylated derivatives on racemization and hydrolysis of (−)‐(S)‐hyoscyamine and (−)‐(S)‐scopolamine were examined kinetically and spectroscopically (NMR). Direct methods, based on a chiral and achiral chromatographic phase system, were used to determine their degradation products and enantiomer composition during stability tests. All different CyDs, except α‐CyD, retarded racemization and hydrolysis. The inclusion of the drug substances in CyDs inhibits the attack of hydroxyl ions and/or water molecules and thus retards the racemization and hydrolysis. The racemization of the tropic acid alkaloids is dependent on the pH and temperature. NMR studies were used to evidence the formation of a soluble 1:1 complex in aqueous solution. © 1993

ISSN:0899-0042    

DOI:10.1002/chir.530050207

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe stereoselectivity of the in vitro dissolution of two commercially available sustained release formulations of rac‐verapamil (rac‐VER) has been investigated. The studies were carried out using a single‐tablet continuous‐flow apparatus and the concentrations of R‐ and S‐VER released from the formulations were measured using enantioselective chromatography on a high performance liquid chromatography (HPLC) chiral stationary phase containing immobilized α1‐acid glycoprotein (Chiral AGP‐column). The data from this study demonstrates that the two formulations have different dissolution profiles and that the amount of drug dissolved was highly dependent on pH. In addition, between pH 3 and 8, the total cumulative amount of R‐VER released was greater than the amount of S‐VER and a statistically significant difference (P<0.01) was detected at pH 6. The results of this study indicate that bioavailability and bioequivalency studies should consider the possibility of enantioselective dissolution when racemic compounds are present in the formulations. ©

ISSN:0899-0042    

DOI:10.1002/chir.530050208

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractpKa1values of 3‐methoxy‐N‐desmethyldiazepam in acetonitrile and methanol containing various acid concentrations were determined by spectrophotometry to be 3.5 and 1.3, respectively. Temperature‐dependent racemization of enantiomeric 3‐methoxy‐N‐desmethyldiazepam in methanol containing 0.5 M H2SO4was studied by circular dichroism spectropolorimetry and the racemization reactions were found to follow apparent first‐order kinetics. Thermodynamic parameters of the racemization reaction were found to be: Eact= 18.8 kcal/mol, and at 25°C: ΔH‡= 18.3 kcal/mol, ΔS‡= −14.8 entropy unit, and ΔG‡= 22.7 kcal/mol, respectively. The racemization had an isotope effect (kH/kD) of 1.6 at 42°C. Based on the results of this report and those of earlier reports by other investigators, a nucleophilically solvated C3 carbocation intermediate resulting from either a P (plus) or an M (minus) conformation is proposed to be an intermediate and responsible for the stereoselective nucleophilic substitution and the subsequent racemization of 3‐methoxy‐N‐desmethyldiazepam e

ISSN:0899-0042    

DOI:10.1002/chir.530050209

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

摘要:

Abstractcis‐ andtrans‐5‐Ethoxy‐1,3‐oxathiolane‐2‐carboxylic acids were obtained in pure form. Thecisisomer was resolved into its enantiomers through diastereoisomeric salt formation with enantiomerically pure α‐methylbenzylamine. Reduction of the salt followed by benzoylation led to 2‐benzoyloxymethyl‐5‐ethoxy‐2(R)‐5(S)‐1,3‐oxathiolane and 2‐benzoyloxymethyl‐5‐ethoxy‐2(S)‐5(R)‐1,3‐oxathiolane, useful intermediates in

ISSN:0899-0042    

DOI:10.1002/chir.530050210

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY

ISSN:0899-0042    

DOI:10.1002/chir.530050211

出版商:Alan R. Liss, Inc.    

年代:1993

数据来源: WILEY