48 results match your criteria hydratropic acid


Reinvestigation of the Absolute Configurations of Chiral β-Mercaptoalkanones Using Vibrational Circular Dichroism and H NMR Analysis.

J Agric Food Chem 2016 Nov 3;64(45):8563-8571. Epub 2016 Nov 3.

Lehrstuhl für Allgemeine Lebensmitteltechnologie, Technische Universität München , Maximus-von-Imhof-Forum 2, D-85354 Freising-Weihenstephan, Germany.

The absolute configurations of chiral β-mercaptoalkanones were previously assigned on the basis of the H NMR anisotropy method using (S)-2-methoxy-2-(1-naphthyl)propionic acid ((S)-MαNP) as the chiral auxiliary. This study presents a reinvestigation of the configurations of 4-mercapto-2-pentanone 1, 4-mercapto-2-heptanone 2, and 2-mercapto-4-heptanone 3. Enantiomers of 1, 2, and 3 were obtained by lipase-catalyzed hydrolyses of the respective acetylthioalkanones. Read More

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November 2016

Analytical Enantioseparation of β-Substituted-2-Phenylpropionic Acids by High-Performance Liquid Chromatography with Hydroxypropyl-β-Cyclodextrin as Chiral Mobile Phase Additive.

J Chromatogr Sci 2016 Apr 10;54(4):593-7. Epub 2016 Jan 10.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, China.

Analytical enantioseparation of five β-substituted-2-phenylpropionic acids by high-performance liquid chromatography with hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral mobile phase additive was established in this paper, and chromatographic retention mechanism was studied. The effects of various factors such as the organic modifier, different ODS C18 columns and concentration of HP-β-CD were investigated. The chiral mobile phase was composed of methanol or acetonitrile and 0. Read More

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Preparative Enantioseparation of β-Substituted-2-Phenylpropionic Acids by Countercurrent Chromatography With Substituted β-Cyclodextrin as Chiral Selectors.

Chirality 2015 Nov 3;27(11):795-801. Epub 2015 Sep 3.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, China.

Preparative enantioseparation of four β-substituted-2-phenylpropionic acids was performed by countercurrent chromatography with substituted β-cyclodextrin as chiral selectors. The two-phase solvent system was composed of n-hexane-ethyl acetate-0.10 mol L-1 of phosphate buffer solution at pH 2. Read More

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November 2015

Cyclosporin A-sensitive cytotoxicity of flurbiprofen non-stereoselectively mediated by cytochrome P450 metabolism in three-dimensional cultured rat hepatocytes.

J Pharm Pharmacol 2015 Oct 23;67(10):1406-15. Epub 2015 Jun 23.

Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, Sanuki, Kagawa, Japan.

Objectives: 2-Arylpropionic acid (profen) drugs are associated with severe hepatotoxicity; however, risk factors are still poorly understood. Acyl-coenzyme A (acyl-CoA) thioesters of profen drugs play a more important role in the covalent binding to rat hepatocyte proteins than the respective acyl-glucuronides. Therefore, we examined whether acyl-glucuronides, acyl-CoA thioesters and oxidative metabolites of profen drugs stereoselectively participated in liver damage. Read More

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October 2015

Application and comparison of high performance liquid chromatography and high speed counter-current chromatography in enantioseparation of (±)-2-phenylpropionic acid.

J Chromatogr A 2013 Mar 23;1281:79-86. Epub 2013 Jan 23.

College of Pharmaceutical Science, Zhengjiang University of Technology, Hangzhou 310032, China.

High performance liquid chromatography (HPLC) and high speed counter-current chromatography (HSCCC) were applied and compared in enantioseparation of 2-phenylpropionic acid (2-PPA) when hydroxypropyl-β-cyclodextrin (HP-β-CD) was used as chiral mobile phase additive. For HPLC, the enantioseparation was achieved on ODS C(18) reverse phase column and the mobile phase was 25 mmol L(-1) HP-β-CD aqueous buffer solution (pH 4.0, adjusted with triethylamine): methanol: glacial acetic acid (85:15:0. Read More

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Chiral carboxylic acids and their effects on melting-point behaviour in co-crystals with isonicotinamide.

Acta Crystallogr B 2008 Dec 14;64(Pt 6):780-90. Epub 2008 Nov 14.

Centre for Supramolecular Chemistry Research, Department of Chemistry, University of Cape Town, Cape Town, South Africa.

The crystal structures of co-crystals of two systems of chiral carboxylic acids, optically active and racemic 2-phenylpropionic acid and 2-phenylbutyric acid, with isonicotinamide are reported to investigate the effects of the chirality of the chiral carboxylic acids on the melting point of the co-crystal complexes. It was found that the racemic co-crystal has a higher melting point than the optically active co-crystal, which correlates with the denser packing arrangement inherent in centrosymmetric space groups. Read More

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December 2008

Differential effects of fibrates on the metabolic activation of 2-phenylpropionic acid in rats.

Drug Metab Dispos 2008 Apr 10;36(4):682-7. Epub 2008 Jan 10.

Department of Biopharmaceutical Sciences, 533 Parnassus Ave., U-68, University of California, San Francisco, CA 94143-0446, USA.

A series of studies were conducted to explore the inductive potential of different fibric acid derivatives on the two alternative metabolic activation pathways of 2-phenylpropionic acid (2-PPA) (a model substrate for profen drugs), namely acyl-CoA formation and acyl glucuronidation, in vivo in rats, and to evaluate whether such treatment could potentially modulate the covalent binding of profens to hepatic protein. After administration of a single dose of 2-PPA (130 mg/kg) to rats pretreated with equimolar doses of clofibric acid (160 mg/kg/day), fenofibrate (260 mg/kg/day), or gemfibrozil (180 mg/kg/day) for 7 days, rat livers were collected and analyzed for covalent binding and hepatic levels of the two reactive metabolites over a 2-h period. Results showed that the three fibrates exhibited very different effects on the hepatic levels of 2-PPA-S-acyl CoA (2-PPA-CoA) in vivo, even though all three significantly increased acyl-CoA synthetase activity in vitro in liver homogenate. Read More

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Hydrogels of dextran containing nonsteroidal anti-inflammatory drugs as pendant agents.

Drug Deliv 2007 Feb;14(2):87-93

Dipartimento di Studi di Chimica e Tecnologia delle Sostanze Biologicamente Attive, Università La Sapienza, Roma, Italy.

The oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal tract side effects. To reduce these effects and improve the therapeutic efficacy, NSAIDs are often formulated as controlled release systems. We have prepared a new formulation consisting of dextran hydrogels containing NSAIDs as pendant agents, through ultraviolet irradiation of solutions of dextran functionalized with methacrylic groups in the presence of the drug derivatized in the same way. Read More

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February 2007

Loading-washout studies of the stereoselective sinusoidal uptake of (R)- and (s)-2-phenylpropionyl acyl glucuronide.

Curr Drug Metab 2006 Oct;7(7):817-26

Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Frome Road, Adelaide, SA 5000, Australia.

The vectorial movement of glucuronide conjugates from blood into bile can be an important elimination route for many drug metabolites, however the intrinsic hydrophilicity of those conjugates may conceptually act to reduce the overall efficiency of that process by limiting the flux of such conjugates across the sinusoidal membrane domain of hepatocytes. In this investigation, the hepatic disposition of the diastereomeric glucuronides of (R)- and (S)-2-phenylpropionic acid (a model "profen" compound) have been studied using the isolated perfused rat liver to establish whether a permeability barrier at the sinusoidal membrane domain (demonstrated previously for those conjugates) is of a sufficient magnitude to impact on the overall biliary excretion of these conjugates. Livers were perfused (30 mL/min) with perfusate containing either (R)-PPA, (S)-PPA, (R)-PPA-Glucuronide or (S)-PPA-Glucuronide in order to determine the dispositional profile of each glucuronide administered to the liver as both a preformed and an hepatically-generated metabolite. Read More

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October 2006

Application of thin-layer chromatography to investigate oscillatory instability of the selected profen enantiomers in dichloromethane.

J Chromatogr Sci 2005 Nov-Dec;43(10):542-8

Institute of Chemistry, Silesian University, 9 Szkolna Street, 40-006 Katowice, Poland.

The usefulness of thin-layer chromatography (TLC) as an efficient measuring technique in the studies of oscillatory trans-enantiomerization of profens from the S to the R configuration (and vice versa) during their storage as 70% ethanol solutions is demonstrated in the literature. S-(+)-ibuprofen, S-(+)-naproxen, and S,R-(+/-)-2-phenylpropionic acid are utilized as the test profens. It is proven possible to show oscillatory instability with the racemic S,R-(+/-)-2-phenylpropionic acid also. Read More

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Stereoselective hepatic disposition of model diastereomeric acyl glucuronides.

J Pharmacokinet Pharmacodyn 2004 Feb;31(1):1-27

Centre for Pharmaceutical Research, School of Pharmaceutical, Molecular and Biomedical Sciences. University of South Australia, Frome Road, Adelaide, South Australia, Australia.

Numerous studies have previously been conducted with the impulse-response isolated perfused rat liver (IR-IPRL) to establish the role of both physiological and physicochemical factors in determining solutes' pattern of hepatic disposition, however the impact of optical isomerism on hepatic disposition has hardly been studied using this methodology. In this study, the IR-IPRL was used to assess the extent of stereoselectivity exhibited by the kinetic processes involved in the hepatic disposition of the diastereomeric acyl glucuronides of (R)- and (S)-2-phenylpropionic acid (i.e. Read More

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February 2004

In vivo mechanistic studies on the metabolic activation of 2-phenylpropionic acid in rat.

J Pharmacol Exp Ther 2003 Apr;305(1):250-6

Department of Biopharmaceutical Sciences, University of California, San Francisco, California, USA.

Two alternative metabolic pathways, acyl glucuronidation and acyl-CoA formation, are implicated in the generation of reactive acylating metabolites of carboxylic acids. Here, we describe studies that determine the relative importance of these two pathways in the metabolic activation of a model substrate, 2-phenylpropionic acid (2-PPA), in vivo in rats. Male Sprague-Dawley rats were pretreated with and without (-)-borneol (320 mg/kg i. Read More

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Enantioselective covalent binding of 2-phenylpropionic Acid to protein in vitro in rat hepatocytes.

Chem Res Toxicol 2002 Nov;15(11):1480-7

Department of Biopharmaceutical Sciences, University of California, San Francisco 94143-0446, USA.

A series of studies was conducted to investigate the potential of (R)- and (S)-2-phenylpropionic acid (2-PPA) to undergo enantioselective covalent binding to protein in freshly isolated rat hepatocytes and to determine whether such covalent binding is dependent on acyl glucuronidation or acyl-CoA formation of 2-PPA. Hepatocytes were incubated with (R,S)-, (R)-, or (S)-[1,2-(14)C(2)]-2-PPA (1 mM), and aliquots of the incubation mixture analyzed for covalent binding, acyl glucuronidation, and acyl-CoA formation over a 3 h period. Covalent binding of 2-PPA to hepatocyte protein was shown to be time-dependent and to be 4. Read More

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November 2002

Studies on the chemical reactivity of 2-phenylpropionic acid 1-O-acyl glucuronide and S-acyl-CoA thioester metabolites.

Chem Res Toxicol 2002 Oct;15(10):1309-17

Department of Biopharmaceutical Sciences, University of California, San Francisco, California 94143-0446, USA.

Chemically reactive species formed from the metabolism of carboxylic acid-containing compounds have been proposed as mediators of their toxic side-effects. Two alternative metabolic pathways known to be involved in the generation of reactive acylating metabolites of carboxylic acids are acyl glucuronidation and acyl-CoA formation. Here, we present studies with 2-phenylpropionic acid focused on evaluating the relative abilities of acyl glucuronides versus acyl-CoA derivatives to transacylate the nucleophilic cysteinyl-thiol of glutathione. Read More

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October 2002

Identification of degradation products of ibuprofen arising from oxidative and thermal treatments.

J Pharm Biomed Anal 2002 Oct;30(3):499-509

Dipartimento di Chimica e Tecnologie Farmaceutiche e Alimentari, Università degli Studi di Genova, Via Brigata Salerno (ponte), 16147 Genova, Italy.

Ibuprofen is a widely utilised analgesic anti-inflammatory drug. It is sensitive to oxidation and photodegradation. In this work, the oxidative and thermal degradations were investigated. Read More

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October 2002

Stereoselective internal acyl migration of 1beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids.

Biol Pharm Bull 2000 Apr;23(4):506-10

School of Pharmacy, Tokyo University of Pharmacy and Life Science, Hachioji, Japan.

Internal acyl migration reactions of 1beta-O-acyl glucuronides of 2-arylpropionic acids (profens) are of interest because of their possible role in covalent binding to serum proteins and consequent allergic reactions. The stereoselective degradation of 1beta-O-acyl glucuronides of enantiomeric 2-phenylpropionic acids (PAs), the basic structures of profens, in phosphate buffer (pH 7.4) at 37 degrees C, has been investigated using HPLC. Read More

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1-(5-Dimethylamino-1-naphthalenesulphonyl)-(S)-3-aminopyrrolidine (DNS-Apy) as a fluorescence chiral labelling reagent for carboxylic acid enantiomers.

Biomed Chromatogr 1997 May-Jun;11(3):137-42

Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.

1-(5-Dimethylamino-1-naphthalenesulphonyl)-(S)-3-aminopyrrolidi ne (DNS-Apy) has been synthesized for the separation of carboxylic acid enantiomers by high-performance liquid chromatography (HPLC) and sensitive detection. The reagent reacts with carboxylic acids at room temperature in the presence of activation agents 2,2'-dipyridyl disulphide (DPDS) and triphenylphosphine (TPP). The maximum emission of the diastereomeric amide derived from (S)-phenylpropionic acid and ketoprofen derivatives of DNS-Apy was at 530 nm with excitation at 340 nm. Read More

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September 1997

Optimization of the chiral inversion of 2-phenylpropionic acid by Verticillium lecanii.

J Pharm Pharmacol 1997 Mar;49(3):263-9

Department of Pharmacy, University of Brighton, Moulsecoomb, UK.

Previous studies have demonstrated that Verticillium lecanii might be used as a microbial model of the inversion of 2-arylpropionic acids in man. This paper describes the optimization of the inversion process in respect of culture medium, pH, cell density and substrate concentration. The study demonstrates that optimum inversion occurs in Sørensen's phosphate buffer at pH 5. Read More

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A mechanistic investigation of the microbial chiral inversion of 2-phenylpropionic acid by Verticillium lecanii.

Chirality 1997 ;9(3):254-60

Department of Pharmacy, University of Brighton, Moulsecoomb, United Kingdom.

Previous investigations have described the development of nongrowing suspensions of Verticillium lecanii as a microbial model of the mammalian chiral inversion of the 2-arylpropionic acids (2-APAs). Mechanistic studies in mammals have shown that inversion involves loss of the alpha-methine proton but retention of the original atoms at the beta-methyl position, and a mechanism has been proposed involving enzymatic epimerisation of acyl-CoA thioester derivatives of the substrate. Inversion of the 2-APAs by V. Read More

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Involvement of arginine 120, glutamate 524, and tyrosine 355 in the binding of arachidonate and 2-phenylpropionic acid inhibitors to the cyclooxygenase active site of ovine prostaglandin endoperoxide H synthase-1.

J Biol Chem 1996 Jan;271(4):2179-84

Department of Biochemistry, Michigan State University, East Lansing 48824, USA.

Examination of the crystal structure of the ovine prostaglandin endoperoxide synthase-1 (PGHS-1)/S- flurbiprofen complex (Picot, D., Loll, P.J. Read More

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January 1996

Lack of stereoselectivity of the peroxisome proliferation induced by 2-phenylpropionic acid: evidence against a role for lipid disturbance in peroxisome proliferation.

Authors:
D Ahmad J Caldwell

Chirality 1994 ;6(5):365-71

Department of Pharmacology and Toxicology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, London, England.

The 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 x 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. Read More

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September 1994

Production of S-(+)-2-phenylpropionic acid from (R,S)-2-phenylpropionitrile by the combination of nitrile hydratase and stereoselective amidase in Rhodococcus equi TG328.

Appl Microbiol Biotechnol 1993 Aug;39(6):720-5

Department of Agricultural Chemistry, Kyoto University, Japan.

A new soil isolate, tentatively identified as Rhodococcus equi TG328, was found to be effective in the production of S-(+)-2-phenylpropionic acid from (R,S)-2-phenylpropionitrile. The conversion is catalysed by two enzymes. First, a nitrile hydratase converts the (R,S)-nitrile to (R,S)-2-phenylpropionamide. Read More

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Microbial metabolism of 2-arylpropionic acids: chiral inversion of ibuprofen and 2-phenylpropionic acid.

Chirality 1993 ;5(8):596-601

Department of Pharmacy, King's College London, United Kingdom.

The metabolism of (R,S)-ibuprofen has been investigated in 24 microbial cultures. Of these Cunninghamella elegans, Mucor hiemalis, and Verticillium lecanii catalyzed the oxidation of the drug to 2-[4-(2-hydroxy-2-methylpropyl)phenyl]propionic acid, a known mammalian metabolite. The extent of metabolism was greatest with V. Read More

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[Stereoselective chronopharmacokinetics of hydratropic acid in rats].

Yao Xue Xue Bao 1993 ;28(12):893-8

Tian jin Institute of Medical and Pharmaceutical Science.

The circadian rhythms of hydratropic acid (HTA) pharmacokinetic parameters were studied by using consinor method. Under standard light-dark cycle, the T1/2 beta and CL of S(+)-HTA, T1/2 beta of R(-)-HTA and CL, MRT of RS (+/-)-HTA were found to have circadian rhythm. Circadian rhythms were also found in the T1/2 beta and AUC of S (+)-HTA, CLS of R(-)-HTA and RS(+/-)-HTA under reverse light--dark cycle. Read More

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[The stereoselectivity of chrono-pharmacokinetic parameters of hydratropic acid in rats].

Yao Xue Xue Bao 1993 ;28(11):817-22

Institute of Medical and Pharmaceutical Science, Tianjin.

The stereoselective chrono-pharmacokinetic parameters of hydratropic acid in rats were studied. The results showed that under standard light-dark cycle pharmacokinetic parameters of T1/2 alpha and CL are stereoselective and under reverse light-dark cycle, parameters T1/2 beta, AUC, CL, Vc and MRT were shown to be stereoselective. To compare the corresponding parameters of the two different light-dark cycles using t-test, no differences were found in most of them. Read More

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Formation of glycine conjugate and (-)-(R)-enantiomer from (+)-(S)-2-phenylpropionic acid suggesting the formation of the CoA thioester intermediate of (+)-(S)-enantiomer in dogs.

Chirality 1992 ;4(6):342-8

Analytical and Metabolic Research Laboratories, Sankyo Co., Ltd., Tokyo, Japan.

It has been proposed that the chiral inversion of the 2-arylpropionic acids is due to the stereospecific formation of the (-)-R-profenyl-CoA thioesters which are putative intermediates in the inversion. Accordingly, amino acid conjugation, for which the CoA thioesters are obligate intermediates, should be restricted to those optical forms which give rise to the (-)-R-profenyl-CoA, i.e. Read More

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January 1993

Substrate specificity and enantioselectivity of arylcarboxylic acid glucuronidation.

Drug Metab Dispos 1988 Jul-Aug;16(4):627-34

A general and sensitive HPLC method using a precolumn switching system was developed for the separation and quantification of the individual diastereoisomeric glucuronides of the 2-phenylpropionic acid optical isomers. Kinetic properties of rat liver glucuronidation of several arylcarboxylic acids (1- and 2-naphthylacetic acids, clofibric acid, (R)-(-)- and (S)-(+)-2-phenylpropionic acids) are characterized. The results show that rat liver microsomes glucuronidate 1-naphthylacetic acid more efficiently than its regioisomer (higher Vmax/Km ratio because of a 6-fold lower Km value). Read More

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December 1988