bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stereoselective binding and activity of oxotremorine analogs at muscarinic receptors in rat brain
Authors: Messer, William S. , Ngur Dan O. , Abuh Yahaya F. , Dokas Linda A. , Ting Shu‐Mei , Hacksell Uli , Nilsson Bjorn M. , Dunbar Philip G. , Hoss Wayne 
Published: January 2005

AbstractThe activities of the enantiomers of BM‐5 were examined to measure muscarinic cholinergic selectivity in the central nervous system. Autoradiographic studies assessed the ability of each enantiomer to inhibit the binding of [3H]‐(R)‐quinuclidinyl benzilate ([3H]‐(R)‐QNB) to muscarinic receptors in the rat brain. (+)‐(R)‐BM‐5 inhibited [3H]‐(R)‐QNB binding to rat brain sections at concentrations below 1.0 μM, while 100‐fold higher concentrations of (—)‐(S)‐BM‐5 were required for comparable levels of inhibition. Analysis of the autoradiograms indicated that both stereoisomers had a similar distribution of high affinity binding sites. Each enantiomer displayed higher affinity for muscarinic receptors in the superior colliculi and lower affinity for receptors in the cerebral cortex and hippocampus. (+)‐(R)‐BM‐5 and oxotremorine inhibited adenylyl cyclase activity in the cerebral cortex with efficacies comparable to that for acetylcholine. (+)‐(R)‐BM‐5 was 26‐fold more potent than (—)‐(S)‐BM‐5 in inhibiting adenylyl cyclase. Oxotremorine‐M and carbamylcholine stimulated phosphoinositide turnover in the cerebral cortex. Oxotremorine had lower activity and (+)‐(R)‐BM‐5 was essentially inactive at comparable concentrations. The difference in activity of the two enantiomers indicates a remarkable stereochemical selectivity for muscarinic receptors. The stereoselectivity index is comparable for both the autoradiographic assays (48) and measures of adenylyl cyclase activity (26) in the cerebral cortex. © 1992 Wiley‐Liss, Inc.
An in vitro study of the stereoselective dissolution of (rac)‐verapamil from two sustained release formulations
Authors: Aubry Anne‐Françcloise , Wainer Irving W. 
Published: January 2005

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. © 1993 Wiley‐Liss, Inc.
In vitro and in vivo irreversible plasma protein binding of beclobric acid enantiomers
Authors: Mayer Sascha , Mutschler Ernst , Spahn‐Langguth Hildegard , Benet Leslie Z. 
Published: January 2005

AbstractAcyl glucuronides are known to be labile conjugates, which undergo hydrolysis and bind irreversibly to proteins. The lipid‐regulating agent (±)‐beclobrate is immediately converted to the free acid after oral administration. Further metabolism leads to formation of the corresponding diastereomeric acyl glucuronides. Beclobric acid glucuronides were quantified by indirect measurement with an HPLC method based on chiral fluorescent derivatization of the carboxylic acid and subsequent normal‐phase chromatography. The renal clearance of unchanged drug is low, with almost all drug excreted into urine as glucuronic acid conjugates. Beclobric acid glucuronide is also detectable in plasma. In vitro degradation studies with beclobric acid glucuronide (at a concentration of 5 μM in 150 mM phosphate buffer pH 7.4) exhibited a minor tendency for acyl migration and hydrolysis, i.e., a higher stability than has been observed for the acyl glucuronides of most other drugs. The in vitro degradation half‐lives of the two beclobric acid β‐1‐O‐acyl glucuronides were 22.7 and 25.7 h. After incubation with pooled plasma and human serum albumin in buffer pH 7.4 irreversible binding was measured in vitro. No significant difference between the two enantiomers was detected with respect to the magnitude of in vitro irreversible binding. In 3 healthy male volunteers the extent of irreversible binding of both beclobric acid enantiomers to plasma proteins was investigated after single and multiple oral doses of racemic beclobrate (100 mg once daily). Irreversible binding of both enantiomers was observed in all volunteers. The adduct densities for (−)‐ and (+)‐beclobric acid after single 100 mg beclobrate doses were 0.147 × 10−4 and 0.177 × 10−4 mol/mol protein. Multipie dosing increased irreversible binding 3‐ to 4‐fold. © 1993 Wiley‐Liss, Inc.
Stereoselectivity in central analgesic action of tocainide and its analogs
Authors: Franchini Carlo , Noja Francesca Chiaia , Corbo Filomena , Lentini Giovanni , Tortorella Vincenzo , Bartolini Alessandro , Ghelardini Carla , Matucci Rosanna , Giotti Alberto 
Published: January 2005

AbstractThe antiarrhythmic drug tocainide (5a) and some related chiral α‐amino and α‐imino anilides (5b–e) were synthesized in optically active form. The antinociceptive effects of the different stereoisomers of these compounds were examined and it was found that the analgesic effect of tocainide is due only to its (−)‐(R)‐enantiomer. Benzyl replacement for methyl group at the stereogenic centre of tocainide causes loss of activity while both enantiomers of the αiminoxilidide 5e and of the strictly related tocainide analog 5d produce an analgesic effect without any stereoselectivity. Pharmacological tests and [3H] quinuclidinyl benzilate ([3H]QNB) binding assay, taken together, seem to show that the antinociceptive effect of (−)‐(R)‐tocainide, like the analgesia induced by lidocaine, procaine, and mexiletine, is due to a central presynaptic cholinergic mechanism of action. © 1993 Wiley‐Liss, Inc.
Enantioselective lipase‐catalyzed ester hydrolysis: Effects on rates and enantioselectivity from a variation of the ester structure
Authors: Bojarski Jacek , Oxelbark Joachim , Andersson Christina , Allenmark Stig 
Published: January 2005

AbstractIn order to make a preliminary study of substituent effects on the rate and enantioselectivity obtained in esterolytic reactions catalyzed by a lipase from Candida rugosa, a series of racemic esters, derived from some α‐alkyl and α‐halo phenylacetic acids, were prepared. The reactions were studied at pH 6.0 and 50°C under which conditions uncatalyzed hydrolysis was relatively slow. Reaction samples were studied at different points of time by means of analytical chiral reversed‐phase liquid chromatography, which permitted the simultaneous determination of product enantiomeric excess and of the degree of total ester hydrolysis. These data were then used to calculate initial rates as well as enantioselectivity. An increase of the steric bulk of the α‐substituent was found to highly decrease the rate of the reaction. On the other hand, rates were higher for the p‐nitrophenyl esters than for the corresponding 2‐chloroethyl esters. Consistently, the enantioselectivity was found to be higher for the latter type of ester. The esters of the α‐halo (bromo and chloro) phenylacetic acids gave mandelic acid as the final product. This was caused by a rapid solvolysis of the α‐halo phenylacetic acid initially formed. © 1993 Wiley‐Liss, Inc.
Chiral stationary phases in concert with homologous chiral mobile phase additives: Push/pull model
Authors: Duff Keith J. , Gray Hannah L. , Gray Rachael J. , Bahler Caroline C. 
Published: January 2005

AbstractA new “push/pull” model has been developed to explain synergistic effects observed in a system in which a chiral stationary phase (CSP) is used in combination with its homologous chiral mobile phase additive (CMPA). The model predicts the beneficial CMPA enantiomer and the counterproductive CMPA enantiomer a priori. Thus, an (R)‐CSP will obtain positive synergism from a homologous (S)‐CMPA and negative synergism from a homologous (R)‐CMPA. The reverse is true for an (S)‐CSP. The importance of structural homology between the CSP and the CMPA is demonstrated. Furthermore, the analysis time is decreased relative to the use of a CSP alone, because the retention time of the analyte peaks decreases when the CMPAs are used. © 1993 Wiley‐Liss, Inc.
Separation of N‐arylthiazoline‐2‐(thi)‐one atropisomers on p‐methylbenzoyl cellulose beads: A factorial design approach
Authors: Roussel Christian , Lehuédé Stephan , Popescu Cristina , Stein Jean‐Louis 
Published: January 2005

AbstractA two level full factorial design has been applied to quantify the effect of three selected structural parameters on the capacity factors and chiral separation of atropisomers in N‐arylthiazoline‐2‐(thi)‐ones derivatives on tris(p‐methylbenzoyl) cellulose beads. The behavior of the two enantiomers is influenced by different factors which might result from different retention sites within the same stationary phase. It appears that the two enantiomers behave independently on the CSP, the order of elution and separation being controlled by a minor steric modification in a very precise location in the molecule for one enantiomer. The methodology of the experimental design allows the comparison of equations generated from data issued from designed compounds. These equations afford much more information than the step by step comparison of individual molecules. In our case, the tris(p‐methylbenzoyl)cellulose beads and microcrystalline cellulose triacetate appear as complementary CSPs for the resolution of atropisomers of the series studied. © 1993 Wiley‐Liss, Inc.
Quantification of trace levels of β‐cyclodextrin and substitution patterns in hydroxypropyl‐β‐cyclodextrin using high‐performance liquid chromatography with polarimetric detection
Authors: Liu Gaoyuan , Goodall David M. , Loran John S. 
Published: January 2005

AbstractA high‐performance liquid chromatographic (HPLC) method has been developed for separation and determination of components in hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD). The method involves separation on an amino‐bonded HPLC column using water–acetonitrile as a mobile phase with a polarimetric HPLC detector for quantification. It provides good selectivity and sensitivity and can also be used to compare different sources of HP‐β‐CD and to measure batch to batch variation. The similarity of the values of molar optical rotation for β‐cyclodextrin (β‐CD) and HP‐β‐CD suggests that a polarimetric HPLC detector may be used with a straightforward area normalization method, to quantify the proportion of β‐CD in any HP‐β‐CD sample. Trace amounts of β‐CD in HP‐β‐CD have been measured to a precision of 0.01%. © 1993 Wiley‐Liss, Inc.
Enantiomeric separations of remoxipride, propranolol, and trimipramine on CHIRAL‐AGP using micellar chromatography and anionic additives
Authors: Haupt Dan , Pettersson Curt , Westerlund Douglas 
Published: January 2005

AbstractThe retentions and enantiomeric resolutions of remoxipride, propranolol, and trimipramine were studied using a CHIRAL‐AGP column with micellar mobile phases and aliphatic, anionic additives. The retentions of the compounds, which in neat buffer solution were very high (k′ > 50), could be decreased to k′ < 10 by adding a mixture of Tween® 20 and heptanoic acid to the mobile phase. The presence of the aliphatic acid was essential in order to increase the enantiomeric selectivity. An efficiency enhancement was obtained by increasing the temperature. With a mobile phase composition optimized for the separation of remoxipride, the possibility of detecting levels of the enantiomeric impurity (R‐remoxipride) down to 0.025% in the drug was demonstrated. © 1993 Wiley‐Liss, Inc.
Chiral separation of amines using reversed‐phased ion‐pair chromatography
Authors: Pettersson Curt , Gioeli Carlo 
Published: January 2005

AbstractThe direct separation of enantiomeric amines has been carried out using a chiral counter ion, (−)‐2,3:4,6,‐di‐O‐isopropylidene‐2‐keto‐L‐gulonic acid [(−)‐DIKGA] dissolved in polar mobile phases, water:methanol or isopropanol:acetonitrile. High separation factors, α = 1.2–1.7, were obtained for several compounds of pharmacological interest such as metoprolol, oxprenolol, remoxipride, mefloquine and p‐OH‐ephedrine. © 1993 Wiley‐Liss, Inc.
Preparative separation of amino acid enantiomers as N‐TFA, O‐isopropyl derivatives by continuous countercurrent gas‐liquid chromatography
Authors: Sato Katsuya , Watabe Katsunori , Ihara Toshihide , Hobo Toshiyuki 
Published: January 2005

AbstractPreparative separation of derivatives of amino acid enantiomers was carried out by a countercurrent gas–liquid chromatography (CCGLC) with chiral liquid phases, N‐stearoyl‐L‐valine tert‐butylamide and/or N‐stearoyl‐L‐leucine tert‐butylamide. In order to make effective use of these phases and also to lower the viscosity, Apiezon C was added as diluent. Through a repeated operation of a temperature gradient, purities more than 99% of leucine and α‐amino butyric acid derivatives were proved to be obtained. © 1993 Wiley‐Liss, Inc.
Enzymatic and chromatographic chiral discrimination of racemic (thio)glycidyl esters: Part I. A chemoenzymatic approach to both enantiomers of thioglycidyl esters
Authors: Martin Arnim A. , Offhauss Ulrike , Wagner Jürgen 
Published: January 2005

AbstractBoth hitherto unknown (+)‐(R)‐ and (−)‐(S)‐thioglycidyl esters, (R)‐(2) and (S)‐(2), have been synthesized with different high enantiomeric excesses (ee) by two routes from the corresponding rac‐glycidyl esters rac‐(1). The first includes a porcine pancreatic lipase (PPL)‐mediated kinetic resolution of these esters followed by sulfuration with practically complete inversion to the (+)‐(R)‐enantiomer (+)‐(R)‐(2) (36–86% ee). (−)‐(S)‐Thioglycidyl esters (−)‐(S)‐(2) are obtained by the reverse reaction sequence (43–80% ee). In the latter case the hydrolysis rate is lower than that of analogous glycidyl esters. Moreover, the dependence of enantiomeric excess on the size of the acyl‐group is of the opposite tendency. Therefore, in both cases suitable selection of the acid residue gives rise to maximum enantioselectivity. The irreversible lipase‐catalyzed acylation of rac‐glycidol and rac‐thioglycidol, however, was found to be a less suitable alternative. The enantiomeric excess of recovered homochiral esters was determined by chiral chromatography using modified cellulose stationary phases (OB, OD). © 1993 Wiley‐Liss, Inc.
Preparative scale enantioseparation of a chiral epoxide: Comparison of liquid chromatography and simulated moving bed adsorption technology
Authors: Nicoud Roger‐Marc , Fuchs Géraldine , Adam Philippe , Bailly Michel , Küsters Ernst , Antia Firoz D. , Reuille Robert , Schmid Emil 
Published: January 2005

AbstractThe feasibility of using simulated moving bed technology (SMB) for chiral separation on cellulose triacetate is demonstrated on the preparative scale: 1 kg of a chiral epoxide has been separated. On comparing SMB technology with conventional liquid chromatography it turns out that the main advantage of SMB lies in the significant reduction of mobile phase consumption. The process design for SMB is made theoretically and the predictions are confirmed by our pilot study. © 1993 Wiley‐Liss, Inc.
Chiral discrimination phenomena in mixed‐ligand copper(II) complexes with amino acids and 1,3‐dicarbonyl compounds
Authors: Davankov Vadim A. , Kurganov Alexander A. , Zhuchkova Ludmila Ya. , Ponomareva Tamara M. 
Published: January 2005

AbstractCircular dichroism (CD) spectra of individual mixed‐ligand copper(II) complexes of 1,3‐dicarbonyl compounds, (1S)‐ or (1R)‐3‐hydroxymethylene camphor, (1S)‐3‐trifluoroacetyl camphor, or (1R)‐2‐hydroxymethylene menthone, and α‐amino acids, alanine, valine, proline, or their N‐alkyl derivatives, were calculated from CD spectra of equilibrium solutions containing the above constituents in methanol or ethylene dichloride. Diastereomeric mixed‐ligand complexes incorporating identical dicarbonyl but enantiomeric N‐alkyl‐α‐amino acid ligands exhibit quasi‐enantiomeric CD spectra. Unsubstituted amino acids, on the contrary, will make no decisive contributions to the net optical activity spectrum of the mixed‐ligand complexes. Formation constants of diastereomeric mixed‐ligand complexes have been calculated from data on disproportionation of the latter into corresponding equally paired complexes. Enantioselectivity was demonstrated to amount to up to 700 cal/mol. Possible steric structures of mixed‐ligand complexes are discussed. © 1993 Wiley‐Liss, Inc.
Enantioselective sequential transformations by use of metal complexes: Tandem‐Knoevenagel‐hetero‐Diels–Alder reactions with new chiral Lewis acids
Authors: Tietze Lutz F. , Saling Peter 
Published: January 2005

AbstractEnantioselective reaction of the aldehydes 1a‐g and the 1,3‐dicarbonyl compound 2 in the presence of the chiral Lewis acid 5, derived from diacetone glucose, leads in a sequential transformation consisting of a Knoevenagel condensation and an intramolecular Diels Alder reaction to the cycloadducts 4a‐g with an ee value up to 88%. The selectivity is strongly dependent upon the temperature and solvent giving best results at room temperature in isodurene; in agreement with the principle of isoinversion, the ee values decrease at lower and higher temperatures. © 1993 Wiley‐Liss, Inc.
Chiral symmetry breaking: Experimental results and computer analysis of a liquid‐phase autoxidation
Authors: Buhse Thomas , Lavabre Dominique , Micheau Jean‐Claude , Thiemann Wolfram 
Published: January 2005

AbstractThe autoxidation of tetralin is treated as a model reaction system to define the applicability of stereospecific autocatalysis. This concept, predicting a spontaneous amplification of enantiomeric excess generated by an autocatalytic chemical reaction, is used in several theoretical models as an explanation for the origin of natural optical activity. The reaction system investigated obeys the basic criteria of these models: a chiral intermediate (tetralin hydroperoxide) is produced from an achiral substrate (tetralin) via an autocatalytic pathway where the feedback mechanism is expected to generate a state of broken chiral symmetry. In order to test the amplification capacity of this reaction a computer analysis of the kinetic scheme is performed. This simulation is derived from the known kinetic scheme of autoxidation and is validated by fitting the experimentally observed data of hydroperoxide evolution. Calculations show that this model allows powerful amplification of enantiomeric excess and a transient amplification of the optical rotation. It is also demonstrated that the model system exhibits pronounced sensitivity toward any loss of absolute configuration of the involved chiral species. Since an amplification effect results exclusively at a high degree of stereoselectivity, it is concluded that stereospecific autocatalysis is possible in systems which show template reactions, crystallization, or colloidal effects. © 1993 Wiley‐Liss, Inc.
Stereoselective distribution of acenocoumarol enantiomers in human plasma: Chiral chromatographic analysis of the ultrafiltrates
Authors: Fitos Ilona , Visy Júlia , Simonyi Miklós , Hermansson Jörgen 
Published: January 2005

AbstractStereoselectivities for the binding of rac‐acenocoumarol to human serum albumin (HSA), α1‐acid glycoprotein (AGP), and human plasma were determined by chiral HPLC analysis of the ultrafiltrates on a Chiral‐AGP column. The results confirmed the previously detected inverse stereoselectivities; for HSA the ratio of the enantiomeric constants was KR/KS ∼ 2, while for AGP it was KR/KS ∼ 0.3. In plasma the contribution of HSA dominates, although in pathological states, elevated AGP levels may compensate for stereoselective distribution. © 1993 Wiley‐Liss, Inc.
Biological significance of the enantiomeric purity of drugs
Authors: Waldeck Bertil 
Published: January 2005

AbstractThe knowledge that enantiomers of chiral compounds may differ widely in biological activity, qualitatively as well as quantitatively, is not new. Nevertheless most of the pharmacological data available to date on chiral drugs are obtained from experiments with racemates which assume that the biological activity generally resides in one of the enantiomers. With the advancements made in stereospecific synthesis and stereoselective analysis of drugs pharmacologists are now offered new possibilities to explore the steric aspects of drug action. This survey will discuss pharmacological data obtained with enantiomer pairs of phenylethylamine derivatives which interact with adrenergic mechanisms. The degree of resolution is seldom specified in published work on stereoselectivity of drugs. In a recent study from our laboratory the enantiomers of the β2‐adrenoceptor agonist formoterol and their diastereomers have been evaluated. We found that the (R;R)‐enantiomer was by far the most potent. However, the relative potencies obtained for the (R;S)‐, (S;R), and (S;S)‐ isomers were critically dependent on the degree of enantiomeric purity. It is concluded that the certainty of potency ratios observed for chiral drugs is limited by the enantiomeric purity and by unspecific effects of the least active enantiomer at very high concentrations. © 1993 Wiley‐Liss, Inc.
Siderophore‐Mediated microbial iron(III) uptake: An exercise in chiral recognition
Authors: Shanzer A. , Libman J. , Yakirevitch P. , Hadar Y. , Chen Y. , Jurkevitch E. 
Published: January 2005

AbstractMolecular recognition by microbial receptors for siderophores [natural iron(III) carriers] is examined with synthetic iron(III) carriers as structural probes. The iron(III) carriers have been designed to reproduce the two essential features of the natural siderophores: the capability to form octahedral iron(III) binding cavities and to fit specific membrane receptors. Specifically, analogs of tripodal ferrichrome and linear ferrioxamines have been prepared and examined. The ferrichrome analogs rely on C3‐symmetric binders that are assembled from triscarboxylates as anchors, amino acids as bridges, and terminal hydroxamate groups as binding sites. The ferrioxamine analogs are based on linear assemblies of three identical monomers, each derived from a chiral amino acid. The deliberate use of animo acid residues as variable building blocks enables us to systematically modify the molecules' envelopes and the preferred absolute configuration of the iron(III) complexes until optimal performance is reached. Examination of the synthetic analogs in Pseudomonas putida demonstrates that the domains around the iron(III) center and their chiral sense dictate the extent of recognition by the membrane receptors. It is also shown that the synthetic siderophore analogs may be designed to either exert a broader, or a more narrow range of microbial activity than the natural siderophores. The implications of these findings are discussed in relation to the possible design of species‐specific antimicrobial agents. © 1993 Wiley‐Liss, Inc.