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1. |
Lack of stereoselectivity of the peroxisome proliferation induced by 2‐phenylpropionic acid: Evidence against a role for lipid disturbance in peroxisome proliferation |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 365-371
Dzulkifly Ahmad,
John Caldwell,
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摘要:
AbstractThe significance of disturbances of lipid metabolism caused by xenobiotic acyl‐CoAs as possible causes of peroxisomal proliferation has been studied with the enantiomers of 2‐phenylpropionic acid (2‐PPA), the (R)‐enantiomer of which is converted to the acyl‐CoA in rats while its (S)‐antipode is not.rac‐2‐PPA (250 mg/kg/day ip × 3) was shown to be an hepatic peroxisomal proliferator in male Sprague–Dawley rats on the basis of increases in microsomal cytochrome P‐450 content and lauric acid hydroxylation and hepatic CN−‐insensitive palmitoyl‐CoA oxidation, a peroxisomal marker activity, while electron microscopy revealed a rise in the peroxisome/mitochondria ratio in hepatocytes. Further studies established the dose–response relationships for these biochemical changes. The (R)‐ and (S)‐enantiomers were administered at a dose of 50 mg/kg/day ip × 3 and both were peroxisome proliferators of very similar potency. The effects of 100 mg/kg/day ip × 3 of the racemate, a dose giving ca. 75% of maximal response, were essentially additive of those of 50 mg/kg/day ip × 3 of its two component isomers. The stereoselectivity of acyl‐CoA formation from the enantiomers of 2‐PPA was confirmed by their differential inhibition of microsomal palmitoyl‐CoA synthesis. Taken together, these data indicate that it is very unlikely that the acyl‐CoA of 2‐PPA plays any role in the peroxisomal proliferation which this compo
ISSN:0899-0042
DOI:10.1002/chir.530060502
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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2. |
Effect of cytochrome P‐450 1A induction on enantioselective metabolism and pharmacokinetics of an aryltrifluoromethyl sulfide in the rat |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 372-377
Etienne Benoît,
Thierry Buronfosse,
Paul Delatour,
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摘要:
AbstractThe pharmacokinetics of the antiparasitic drug toltrazuril (1‐methyl‐3‐[3‐methyl‐4‐[4‐[trifluoromethyl]thio]phenoxy]phenyl‐1,3,5‐ triazine‐2,4,6(1H,3H,5H)‐trione) were studied in the rat following pretreatment with 3‐methylcholanthrene, an inducer of rat liver cytochrome P‐450 1A. The induction markedly modified the pharmacokinetics of the compound, leading to a decrease in the AUC value for toltrazuril sulfoxide. The results were explained on the basis of previous results from our laboratory relating to the product enantioselectivity of the formation of the sulfoxide and the substrate enantioselectivity of the subsequent formation of the sulfon
ISSN:0899-0042
DOI:10.1002/chir.530060503
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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3. |
Investigation of the enantioselectivity and enantiomeric elution order of some piperidine‐2,6‐dione drugs on chiralcel OD column |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 378-381
Hassan Y. Aboul‐Enein,
Vince Serignese,
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摘要:
AbstractThe enantioselectivity and enantiomeric separation of five racemic piperidine‐2,6‐dione compounds, on the cellulose tris(3,5‐dimethylphenyl carbamate) chiral stationary phase Chiralcel OD‐CSP were investigated under the same chromatographic conditions. This class of drugs includes glutethimide, aminoglutethimide, cyclohexylaminoglutethimide, pyridoglutethimide, and phenglutarimide. The results revealed that chiral recognition and the binding sites of these drugs on the Chiralcel OD column are similar, regardless of the absolute configuration of the individual enantiomers. A possible chiral recognition mechanism(s) for this class of drugs and the CSP is presented. © 1994 Wiley
ISSN:0899-0042
DOI:10.1002/chir.530060504
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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4. |
Absolute configuration and biological activity of mequitamium iodide enantiomers |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 382-388
Cristina Di Bugno,
Paolo Dapporto,
Raffaello Giorgi,
Stefano Manzini,
Paola Paoli,
Alessandro Subissi,
Federico Arcamone,
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摘要:
AbstractThe enantiomers of 1‐methyl‐3‐(10H‐phenothiazine‐10‐ylmethyl)‐1‐azoniabicyclo[2,2,2]octane iodide (1) were prepared by chiral chromatographic resolution of the precursor mequitazine (2). The (+)‐(S)‐enantiomer1bis 10‐fold more potent than (−)‐(R)‐enantiomer1aas a histamine antagonist, while the two enantiomers show the same antimuscarinic activity in vitro. The absolute configuration of the more active dextrorotatory isomer has been determined by X‐ray analysis. Conformational analysis and molecular modeling suggest that the (+)‐(S)‐enantiomer can adopt a conformation similar to that attributed to the receptor binding conformers of classical antih
ISSN:0899-0042
DOI:10.1002/chir.530060505
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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5. |
Preparation and configuration of racemic and optically active analgesic dialkylaminoalkylnaphthalenes |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 389-399
Victor Ghislandi,
Ornella Azzolina,
Simona Collina,
Eugenio Paroli,
Letizia Antonilli,
Giuseppe Giuseppetti,
Carla Tadini,
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摘要:
AbstractThe alkylaminoalkylnaphthalene3shows interesting opioid‐like analgesic properties, μ‐selective ligand competition, and enkephalin hydrolyzing enzyme inhibition.3possesses two chiral centers and can exist as two racemic pairs and four diastereomers. Since the binding of opioids with the receptor is stereoselective, it was important to have the two racemic pairs as well as the four diastereomers. In this paper the synthesis of the (1R,2R/1S,2S)‐ and (1R,2S/1S,2R)‐racemates and the (1R,2R)‐ and (1S,2S)‐enantiomers of the 1‐ethyl‐1‐hydroxy‐1‐[2‐(6‐hydroxynaphthyl)]‐2‐methyl‐3‐dimethylaminopropane3is considered and the determination of absolute configuration is described. The (1R,2R/1S,2S)‐3and (1R,2S/1S,2R)‐3racemates and the (1R,2R)‐3and (1S,2S)‐3enantiomers were prepared by reaction of the racemic and optically active 1‐dimethylamino‐2‐methylpentan‐3‐one2, respectively, with the lithiation product obtained from 2‐bromo‐6‐tetrahydropyranyloxynaphthalene and acidic hydrolysis. The optical resolution of aminoketone2was carried out via fractional crystallization of salts (+)‐ and (−)‐dibenzoyltartrates. The configuration of the optically active compounds was determined by X‐ray analysis of a crystal of (+)‐(1R,2R)‐3· HCl · H2O. Preliminary pharmachological tests showed that (+)‐(1R,2R)‐3enantiomer is able to induce opioid‐like analgesia with a relative potency 2.5 times tha
ISSN:0899-0042
DOI:10.1002/chir.530060506
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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6. |
Racemisation of drug enantiomers by benzylic proton abstraction at physiological pH |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 400-404
Christopher Pepper,
H. John Smith,
Kevin J. Barrell,
Paul J. Nicholls,
Michael J. E. Hewlins,
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摘要:
AbstractThe enantiomers of the aromatase inhibitors 3‐(4‐aminophenyl)‐pyrrolidine‐2,5‐dione (WSP‐3,II), its N‐pentyl derivative (III), and the antifungal econazole (IV), all possessing a benzylic proton at the chiral centre, are rapidly racemised in vitro in phosphate buffer (0.01M) at pH 7.4 and 23°C witht½values of 7, 6, and 5 h respectively. In vivo studies in rats show that (+)‐econazole is racemised after intraperitoneal injection witht½= 1.24h. The enantiomers of the antifungal 1‐[(benzofuran‐2‐yl)‐4‐chlorophenylmethyl] imidazole (V) were stable at pH 7.4, attributable to steric hindrance to carbanion formation in the racemisation
ISSN:0899-0042
DOI:10.1002/chir.530060507
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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7. |
Influence of endotoxin on the stereoselective pharmacokinetics of oxprenolol, propranolol, and verapamil in the rat |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 405-410
Martine E. Laethem,
Frans M. Belpaire,
Pascal Wijnant,
Marie‐Thérèse Rosseel,
Marc G. Bogaert,
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摘要:
AbstractThe influence of endotoxin‐induced inflammation on the enantioselective pharmacokinetics of propranolol, oxprenolol, and verapamil, which bind to α1‐acid glycoprotein, was studied in the rat. The racemic mixtures were given orally. In the control animals, for propranolol and oxprenolol, the plasma concentrations of the (R)‐enantiomer were higher than those of the (S)‐enantiomer, while for verapamil the reverse was true. Protein binding and intrinsic clearance are the main factors responsible for this enantioselectivity. After endotoxin treatment, for the three drugs tested the plasma concentrations and the plasma binding of both enantiomers were significantly increased. This effect was more pronounced for (R)‐propranolol, (R)‐oxprenolol, and (S)‐verapamil than for their respective antipodes. The enantioselective effect of endotoxin on the plasma concentrations of the drugs studied seems mainly due to the enantioselective increase in binding to α1‐acid glycoprotein. © 19
ISSN:0899-0042
DOI:10.1002/chir.530060508
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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8. |
The chemical and thermal stability of the acetamido group of (R)‐ and (S)‐atenolol: Synthetic and chromatographic studies |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 411-419
Oliver P. Kleidernigg,
Norbert M. Maier,
Georg Uray,
Wolfgang Lindner,
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摘要:
AbstractThe chemical stability of the acetamido moiety of the β‐blocker atenolol toward possible dehydration causing a nitrile formation during an acid‐catalyzed chiral derivatization procedure withO,O′‐(R,R)‐diacylated tartaric acid anhydrides was elucidated. All the necessary reference compounds including the oxazolidine‐2‐one derivatives of the respective aminopropanols were synthesized, their structures confirmed by various spectroscopic methods, and chromatographically compared using HPLC and GC‐MS. In the course of this work it was shown that the acetamido moiety of atenolol is quite stable toward dehydrating agents but shows a significant thermolability, e.g., in the injection system of a GC, which leads to the dehydrated form of atenolol namely, “nitriloatenolol.” ©
ISSN:0899-0042
DOI:10.1002/chir.530060509
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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9. |
Stereoisomeric flavour compounds LXVII. 2‐, 3‐, and 4‐Alkyl‐branched acids, part 1: General approach to the synthesis of the enantiopure acids |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 420-426
Volker Karl,
Astrid Kaunzinger,
Jutta Gutser,
Petra Steuer,
Jorge Angles‐Angel,
Armin Mosandl,
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摘要:
AbstractA general approach to the synthesis of 2‐, 3‐, and 4‐alkyl‐branched acids of high enantiomeric purity is described. The enantiopure 2‐alkyl‐branched acids are prepared via liquid chromatographic resolution of diastereomeric phenylglycinol amides and their absolute configuration is deduced from the1H‐NMR data of the separated diastereomers. Chain elongation methods, by Arndt–Eistert synthesis, via 2‐alkylated alkyl carbonitrile or by malonic ester synthesis, are used to prepare 3‐ and 4‐alkyl‐branched acids of high configurational purity and known absolute configuration starting from the enantiomeric 2‐alkyl‐branched ac
ISSN:0899-0042
DOI:10.1002/chir.530060510
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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10. |
Stereoisomeric flavour compounds LXVIII. 2‐, 3‐, and 4‐Alkyl‐branched acids, part 2: Chirospecific analysis and sensory evaluation |
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Chirality,
Volume 6,
Issue 5,
1994,
Page 427-434
Volker Karl,
Jutta Gutser,
Armin Dietrich,
Birgit Maas,
Armin Mosandl,
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摘要:
AbstractEnantioselective GC analysis of 4‐ethyloctanoic and 4‐methylheptanoic acid, using heptakis(2,3‐di‐O‐methyl‐6‐O‐tert‐butyldimethylsilyl)‐β‐cyclodextrin as the chiral stationary phase, is described and the sensory properties of several 4‐alkyl‐branched acids, using gas chromatography‐olfactometry (GC‐O) equipment and octakis(2,3‐di‐O‐methyl‐6‐tert‐butyldimethylsilyl)‐γ‐cyclodextrin as the stationary phase, are evaluated. The chirospecific analysis of various 2‐, 3‐, and 4‐alkyl‐branched acids from commercially available Roman chamomile (Chamaemelum nobile(L.) Allioni), Parmesan cheese, and subcutaneous mutton adipose tissue, using either GC‐GC (MDGC) or GC‐
ISSN:0899-0042
DOI:10.1002/chir.530060511
出版商:Alan R. Liss, Inc.
年代:1994
数据来源: WILEY
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