- Synthesis of sterically hindered polychlorinated biphenyl derivatives
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A series of sterically hindered (methoxylated) polychlorinated biphenyl derivatives were synthesized using the Suzuki and the Ullmann coupling reactions. The Suzuki coupling with Pd(dba)2-dicyclohexylphosphino-2,6- dimethoxybiphenyl (DPDB) gave better yields (65-98%) compared to the classic Ullmann coupling reaction (20-38%). Despite the reactive catalyst system, no significant coupling with aromatic chlorine substituents was observed. Crystal structure analysis of four PCB derivatives revealed solid state dihedral angles ranging from 69.7 to 81.0, which indicates that these highly ortho-substituted PCB derivatives have some conformational flexibility. Georg Thieme Verlag Stuttgart.
- Joshi,Vyas,Duffel,Parkin,Lehmler
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scheme or table
p. 1045 - 1054
(2011/06/20)
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- Syntheses and characterization of the acyl glucuronide and hydroxy metabolites of diclofenac
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In humans, metabolism of the commonly used nonsteroidal antiinflammatory drug diclofenac 1 yields principally the 4′-hydroxy 2, 5-hydroxy 3, and acyl glucuronide 4 metabolites. All three metabolites have been implicated in rare idiosyncratic adverse react
- Kenny, Jane R.,Maggs, James L.,Meng, Xiaoli,Sinnott, Deborah,Clarke, Stephen E.,Park, B. Kevin,Stachulski, Andrew V.
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p. 2816 - 2825
(2007/10/03)
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- 2,2',3,3',6,6'-Hexachlorobiphenyl hydroxylation by active site mutants of cytochrome P450 2B1 and 2B11
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The structural basis of species differences in cytochrome P450 2B- mediated hydroxylation of 2,2',3,3',6,6'-hexachlorobiphenyl (236HCB) was evaluated by using 14 site-directed mutants of cytochrome P450 2B1 and three point mutants of 2B11 expressed in Escherichia coli. To facilitate metabolite identification, seven possible products, including three hydroxylated and four dihydroxylated hexachlorobiphenyls, were synthesized by direct functionalization of precursors and Ullmann and crossed Ullmann reactions. HPLC and GCfMS analysis and comparison with authentic standards revealed that 2B1, 2B11, and all their mutants produced 4,5-dihydroxy-236HCB and 5-hydroxy- 236HCB, while 2B11 L363V and 2B1 I114V mutants also catalyzed hydroxylation at the 4-position. The amount of products formed by 2B1 mutants I114V, F206L, L209A, T302S, V363A, V363L, V367A, I477A, I477L, G478S, I480A, and I480L was smaller than that of the wild type. I477V exhibited unaltered 236HCB metabolism, and I480V produced twice as much dihydroxy product as the wild type. For 2B11, substitution of Val-114 or Asp-290 with Ile decreased the product yields. Replacement of Leu-363 with Val dramatically altered the profile of 236HCB metabolites. In addition to an increase in the overall level of hydroxylation, the mutant mainly catalyzed hydroxylation at the 4- position. Incubation of P450 2B1 with 5-hydroxy-236HCB produced 4,5- dihydroxy-236HCB, which indicates that 4,5-dihydroxy-236HCB may be formed by a direct hydroxylation of 5-hydroxy-236HCB. The findings from this study demonstrate the importance of residues 114, 206, 209, 302, 363, 367, 477, 478, and 480 in 2B1 and 114, 290, and 363 in 2B11 for 236HCB metabolism.
- Waller, Stephen C.,He, You Ai,Harlow, Greg R.,He, You Qun,Mash, Eugene A.,Halpert, James R.
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p. 690 - 699
(2007/10/03)
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- Synthesis of deuterium labelled 4'-hydroxydiclofenac
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Diclofenac is a potentially useful substrate for the study of drug-drug interactions caused by modulation of the activity of specific isoforms of cytochrome P450. The synthesis of a deuterium labelled version of its principal human metabolite, 4'-hydroxydiclofenac, for use as an internal standard in LC-MS-MS studies, is described.
- Waterhouse, Ian
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p. 1075 - 1083
(2007/10/03)
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- Hydrohalogenation of 1,4-Benzoquinone Mono- and Bis(O-acyloximes)
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Hydrohalogenation of 1,4-benzoquinone O-acyloximes involves intermediate formation of corresponding 1,4-benzoquinone monooximes and hydroxyamino derivatives. The final hydrochlorination products are 2,6-dichloro-4-alkoxyanilines, hydrobromination yields 3,5-dibromo-4-aminophenol as the final product. O-Acyl- and O,O′-diacyl-1,4-benzoquinone dioximes do not undergo hydrohalogenation.
- Avdeenko,Glinyanaya
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p. 1154 - 1159
(2007/10/03)
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- Magenta couplers
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Magenta couplers of the 5-pyrazolone type which have a phenylcarbamylamino substituent in the 3-position of the pyrazolone nucleus and which have, as a substituent in the 1-position of the pyrazolone nucleus, a 2', 4'-dihalo-6'-alkoxyphenyl group or a 2', 6'-dihalo-4'-alkoxyphenyl group.
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