The Experts below are selected from a list of 303 Experts worldwide ranked by ideXlab platform
Matthias Schwab - One of the best experts on this subject based on the ideXlab platform.
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udp glucuronosyltransferase ugt polymorphisms affect atorvastatin Lactonization in vitro and in vivo
Clinical Pharmacology & Therapeutics, 2010Co-Authors: Stephan Riedmaier, Kathrin Klein, Ute Hofmann, Jenni E. Keskitalo, Pertti J. Neuvonen, Matthias SchwabAbstract:The response to statins shows large interpatient variability. Atorvastatin δ-lactone is pharmacologically inactive but has been associated with toxicity. We investigated the role of UDP-glucuronosyltransferases (UGTs) in atorvastatin Lactonization. In human liver microsomes, Lactonization was correlated with UGT1A3 (rs = 0.61, P < 0.0001) but not with UGT1A1. Surprisingly, lactone formation was significantly higher in carriers of UGT1A1*28, an allele that is associated with lower UGT1A1 expression. We show that this inverse correlation is due to extensive linkage disequilibrium in the UGT1A locus and that several UGT1A3 haplotypes are associated with strong increases in UGT1A3 expression in vitro. Analyses of the pharmacokinetic parameters of atorvastatin and metabolites in genotyped volunteers confirmed that there is an increase in atorvastatin Lactonization in carriers of UGT1A3*2 in vivo. The potential of UGT genotyping to identify patients who are at increased risk for failure of therapy and/or adverse effects of statins warrants further investigation. Clinical Pharmacology & Therapeutics (2010) 87 1, 65–73. doi:10.1038/clpt.2009.181
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UDP‐Glucuronosyltransferase (UGT) Polymorphisms Affect Atorvastatin Lactonization In Vitro and In Vivo
Clinical pharmacology and therapeutics, 2009Co-Authors: Stephan Riedmaier, Kathrin Klein, Ute Hofmann, Jenni E. Keskitalo, Pertti J. Neuvonen, Matthias Schwab, Mikko Niemi, Ulrich M. ZangerAbstract:The response to statins shows large interpatient variability. Atorvastatin δ-lactone is pharmacologically inactive but has been associated with toxicity. We investigated the role of UDP-glucuronosyltransferases (UGTs) in atorvastatin Lactonization. In human liver microsomes, Lactonization was correlated with UGT1A3 (rs = 0.61, P < 0.0001) but not with UGT1A1. Surprisingly, lactone formation was significantly higher in carriers of UGT1A1*28, an allele that is associated with lower UGT1A1 expression. We show that this inverse correlation is due to extensive linkage disequilibrium in the UGT1A locus and that several UGT1A3 haplotypes are associated with strong increases in UGT1A3 expression in vitro. Analyses of the pharmacokinetic parameters of atorvastatin and metabolites in genotyped volunteers confirmed that there is an increase in atorvastatin Lactonization in carriers of UGT1A3*2 in vivo. The potential of UGT genotyping to identify patients who are at increased risk for failure of therapy and/or adverse effects of statins warrants further investigation. Clinical Pharmacology & Therapeutics (2010) 87 1, 65–73. doi:10.1038/clpt.2009.181
Apparao Satyam - One of the best experts on this subject based on the ideXlab platform.
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accidental discovery of a longer range vinylogous pummerer type Lactonization formation of sulindac sulfide lactone from sulindac
Tetrahedron Letters, 2011Co-Authors: Somnath Halder, Apparao SatyamAbstract:Unexpected formation of sulindac sulfide lactone occurred when sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous sulindac sulfide and indomethacin did not undergo such Lactonization under similar reaction conditions. We believe that the sulfoxide function in sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed Lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.
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Accidental discovery of a ‘longer-range’ vinylogous Pummerer-type Lactonization: formation of sulindac sulfide lactone from sulindac
Tetrahedron Letters, 2011Co-Authors: Somnath Halder, Apparao SatyamAbstract:Unexpected formation of sulindac sulfide lactone occurred when sulindac was treated with oxalyl chloride and triethylamine. Structurally analogous sulindac sulfide and indomethacin did not undergo such Lactonization under similar reaction conditions. We believe that the sulfoxide function in sulindac plays a pivotal role possibly via a ‘longer-range’ vinylogous Pummerer-type reaction as a driving force for the observed Lactonization. The structure of the lactone was confirmed by single crystal X-ray analysis.
Jian Zhou - One of the best experts on this subject based on the ideXlab platform.
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Metal-free tandem Friedel-Crafts/Lactonization reaction to benzofuranones bearing a quaternary center at C3 position.
The Journal of organic chemistry, 2012Co-Authors: Long Chen, Feng Zhou, Taoda Shi, Jian ZhouAbstract:A metal-free tandem Friedel–Crafts/Lactonization reaction to 3,3-diaryl or 3-alkyl-3-aryl benzofuranones catalyzed by HClO4 was reported. A variety of tertiary α-hydroxy acid esters could readily react with substituted phenols to afford the desired products in rich diversity. The synthetic utility of the products was demonstrated by the synthesis of polycyclic compounds. 1H NMR studies supported that this tandem reaction proceeded via tandem Friedel–Crafts/Lactonization sequence.
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metal free tandem friedel crafts Lactonization reaction to benzofuranones bearing a quaternary center at c3 position
Journal of Organic Chemistry, 2012Co-Authors: Long Chen, Feng Zhou, Taoda Shi, Jian ZhouAbstract:A metal-free tandem Friedel–Crafts/Lactonization reaction to 3,3-diaryl or 3-alkyl-3-aryl benzofuranones catalyzed by HClO4 was reported. A variety of tertiary α-hydroxy acid esters could readily react with substituted phenols to afford the desired products in rich diversity. The synthetic utility of the products was demonstrated by the synthesis of polycyclic compounds. 1H NMR studies supported that this tandem reaction proceeded via tandem Friedel–Crafts/Lactonization sequence.
Stephan Riedmaier - One of the best experts on this subject based on the ideXlab platform.
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udp glucuronosyltransferase ugt polymorphisms affect atorvastatin Lactonization in vitro and in vivo
Clinical Pharmacology & Therapeutics, 2010Co-Authors: Stephan Riedmaier, Kathrin Klein, Ute Hofmann, Jenni E. Keskitalo, Pertti J. Neuvonen, Matthias SchwabAbstract:The response to statins shows large interpatient variability. Atorvastatin δ-lactone is pharmacologically inactive but has been associated with toxicity. We investigated the role of UDP-glucuronosyltransferases (UGTs) in atorvastatin Lactonization. In human liver microsomes, Lactonization was correlated with UGT1A3 (rs = 0.61, P < 0.0001) but not with UGT1A1. Surprisingly, lactone formation was significantly higher in carriers of UGT1A1*28, an allele that is associated with lower UGT1A1 expression. We show that this inverse correlation is due to extensive linkage disequilibrium in the UGT1A locus and that several UGT1A3 haplotypes are associated with strong increases in UGT1A3 expression in vitro. Analyses of the pharmacokinetic parameters of atorvastatin and metabolites in genotyped volunteers confirmed that there is an increase in atorvastatin Lactonization in carriers of UGT1A3*2 in vivo. The potential of UGT genotyping to identify patients who are at increased risk for failure of therapy and/or adverse effects of statins warrants further investigation. Clinical Pharmacology & Therapeutics (2010) 87 1, 65–73. doi:10.1038/clpt.2009.181
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UDP‐Glucuronosyltransferase (UGT) Polymorphisms Affect Atorvastatin Lactonization In Vitro and In Vivo
Clinical pharmacology and therapeutics, 2009Co-Authors: Stephan Riedmaier, Kathrin Klein, Ute Hofmann, Jenni E. Keskitalo, Pertti J. Neuvonen, Matthias Schwab, Mikko Niemi, Ulrich M. ZangerAbstract:The response to statins shows large interpatient variability. Atorvastatin δ-lactone is pharmacologically inactive but has been associated with toxicity. We investigated the role of UDP-glucuronosyltransferases (UGTs) in atorvastatin Lactonization. In human liver microsomes, Lactonization was correlated with UGT1A3 (rs = 0.61, P < 0.0001) but not with UGT1A1. Surprisingly, lactone formation was significantly higher in carriers of UGT1A1*28, an allele that is associated with lower UGT1A1 expression. We show that this inverse correlation is due to extensive linkage disequilibrium in the UGT1A locus and that several UGT1A3 haplotypes are associated with strong increases in UGT1A3 expression in vitro. Analyses of the pharmacokinetic parameters of atorvastatin and metabolites in genotyped volunteers confirmed that there is an increase in atorvastatin Lactonization in carriers of UGT1A3*2 in vivo. The potential of UGT genotyping to identify patients who are at increased risk for failure of therapy and/or adverse effects of statins warrants further investigation. Clinical Pharmacology & Therapeutics (2010) 87 1, 65–73. doi:10.1038/clpt.2009.181
Hiroyuki Akita - One of the best experts on this subject based on the ideXlab platform.
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Intramolecular reaction of a phenonium ion. Novel Lactonization of 4-aryl-5-tosyloxypentanoates and 4-aryl-5-tosyloxyhexanoates concomitant with a phenyl rearrangement.
The Journal of organic chemistry, 2002Co-Authors: Shinji Nagumo, Machiko Ono, Yo-ichiro Kakimoto, Tsuneo Furukawa, Tomoaki Hisano, Megumi Mizukami, Norio Kawahara, Hiroyuki AkitaAbstract:The novel Lactonizations of methyl 4-aryl-5-tosyloxypentanoate 1 and 4-aryl-5-tosyloxyhexanoate 3 concomitant with a phenyl rearrangement are reported. The Lactonizations were promoted by silica gel or heating in various solvents. By examining the effects of substituents of the aromatic ring on the reactivity, it was found that the reaction proceeded via a phenonium ion. This finding was supported by the stereochemical results for the Lactonization of optical active 1. Silica gel-promoted Lactonization of 1 gave only γ-lactone 2, whereas that of 3 afforded γ-lactone 4 and δ-lactone 5. These Lactonizations proved to be kinetically controlled. On the other hand, when 3c was heated in CH3NO2 at 70 °C, the highly selective formation of 4c was observed. Further detailed experiments confirmed that the thermal Lactonization in CH3NO2 was thermodynamically controlled.
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Lactonization of methyl 4-aryl-5-tosyloxyhexanoate via a phenonium ion
Tetrahedron Letters, 1998Co-Authors: Shinji Nagumo, Machiko Ono, Yo-ichiro Kakimoto, Tsuneo Furukawa, Tomoaki Hisano, Norio Kawahara, Sanae Takeda, Hiroyuki AkitaAbstract:Abstract Lactonization of methyl 4-aryl-5-tosyloxy hexanoate 3 via a phenonium ion gave γ-lactone 4 selectively under thermodynamical conditions while it afforded δ-lactone 5 preferentially under kinetic conditions.
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Novel Lactonization induced by the phenonium ion
Tetrahedron Letters, 1997Co-Authors: Shinji Nagumo, Machiko Ono, Tsuneo Furukawa, Hiroyuki AkitaAbstract:Abstract Silica gel promotes the Lactonization and the concomitant aryl rearrangement of 4-aryl-5-tosyloxy pentanoates ( 3c-j ) to give γ-lactones along with complete inversion in high yields.
