Benzophenone metabolism. I. Isolation of p-hydroxybenzophenone from rat urine

Stocklinski, Andrew W.; Ware, Oliver B.; Oberst, Thomas J.

doi:10.1016/0024-3205(80)90152-6

Cited by 13 publications

(3 citation statements)

References 6 publications

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“…All of the 4-hydroxylated benzophenones (No. 4,(6)(7)(8)(9)(10)(11)(12)16,20), which had a phenol ring, and also had a benzoyl group as a hydrophobic moiety at the p-position, had rather strong activity. However, benzophenones without a hydroxyl group at the 4-position were negative (No.…”

Section: As Shown Inmentioning

confidence: 99%

Estrogenic Activities of UV Stabilizers Used in Food Contact Plastics and Benzophenone Derivatives Tested by the Yeast Two-Hybrid Assay

Kawamura¹,

Ogawa²,

Nishimura³

et al. 2003

JOURNAL OF HEALTH SCIENCE

113

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UV stabilizers used in food contact plastics were tested for their estrogenic activity by the yeast two-hybrid assay. Among 11 kinds of UV stabilizers, 2-hydroxy-4-methoxybenzophenone and 2,2′-dihydroxy-4-methoxybenzophenone displayed estrogenic activity, while salicylate, benzoate and benzotriazole derivatives and a benzophenone derivative had no activity. Therefore, benzophenone and 19 kinds of hydroxylated derivatives were further studied. Of these, 15 chemicals showed estrogenic activity. The strongest activity was by 2,4-dihydroxybenzophenone, 4hydroxy-4′-chlorobenzophenone, 4-hydroxybenzophenone and 2,3,4-trihydroxybenzophenone. Their activities were stronger than that of bisphenol A which was recognized as a potential endocrine disruptor. The following structureactivity relationships of benzophenones were obtained. The activity of the benzophenones with a hydroxyl group at the 3 or 4-position was positive and rather strong, though that of other benzophenones without a hydroxyl group at the 3 or 4-position was negative or weakly positive. The effect of the hydroxyl group in the phenol moiety were in order of 4-> 3->> 2-position. A hydroxyl group added at the 2-position of the 4-hydroxylated benzene ring enhanced the activity. On the other hand, a hydroxyl group added to the benzene ring of the hydrophobic moiety reduced the binding, while the chloro group enhanced it. Some of these relationships might possibly hold for other estrogenic chemicals that possess two benzene rings.

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Section: As Shown Inmentioning

confidence: 99%

Estrogenic Activities of UV Stabilizers Used in Food Contact Plastics and Benzophenone Derivatives Tested by the Yeast Two-Hybrid Assay

Kawamura¹,

Ogawa²,

Nishimura³

et al. 2003

JOURNAL OF HEALTH SCIENCE

113

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“…Some are also produced in the body as the metabolites of benzophenone and its derivatives. 2,3,11,12) In the previous paper, 13) we tested the estrogenic activities of benzophenone and 19 hydroxylated benzophenones using the yeast two-hybrid assay. Among them, fifteen expressed estrogenic activity, some showed a higher activity than bisphenol A, and the results provided an indication of the structure-activity relationships.…”

Section: Introductionmentioning

confidence: 99%

Estrogenic and Anti-Androgenic Activities of Benzophenones in Human Estrogen and Androgen Receptor Mediated Mammalian Reporter Gene Assays

Kawamura¹,

Mutsuga²,

Kato

et al. 2005

JOURNAL OF HEALTH SCIENCE

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“…Special attention was given to the question to which extent a methoxymethyl side chain in position 2 would influence the metabolic attack thus modifying the biotransformation known from other benzodiazepines [8,9,10,11,12].…”

Section: Introductionmentioning

confidence: 99%

Metabolism and pharmacokinetics of metaclazepam (Talis®), Part III: Determination of the chemical structure of metabolites in dogs, rabbits and men

Borchers¹,

Achtert²,

Hausleiter³

et al. 1984

European Journal of Drug Metabolism and Pharmacokinetics

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The metabolism of 7-bromo-1-methyl-2-methoxymethyl-5-(2'-chlorophenyl)-2, 3-dihydro-1H-1,4-benzodiazepine (metaclazepam, Talis) in animals and men is described. Based upon mass spectrometry fifteen metabolites could be identified. Qualitative and quantitative differences in the biotransformation products of metaclazepam in comparison with the well known metabolites of other drugs in the 1,4-benzodiazepine class could be demonstrated. Metabolites with a benzodiazepine-2-one structure representing the most characteristic feature of other 1,4-benzodiazepines and their metabolites, were found in trace amounts only. The major metabolic pathways of metaclazepam led via stepwise demethylation of the O-methyl and/or the N-methyl group to O-demethyl-metaclazepam (M 2), N-demethyl-metaclazepam (M 7) and bis-demethyl-metaclazepam (M 6). Further aromatic hydroxylation yielded the metabolite M 1. Two metabolites with amino-benzophenone structure (M 5, M 8) which are in general known to result from other 1,4-benzodiazepines could be detected. Additionally a 3-oxo-benzodiazepine (M 4) was found. Minor biotransformation pathways led to a chlorophenyl-bromo-benzodiazepine (M 9) by loss of the side chain from bis-demethyl-metaclazepam and N-demethyl-metaclazepam. By further oxidation and degradation the 2-oxo-benzodiazepine M 10 and the dihydro-quinazoline M 12 were formed. The respective N-methylated metabolites M 13 and M 16 were possibly generated by the same pathway. Still open is the formation of M 15, a 1-methyl-3-hydroxy-4-(2'-chlorophenyl)-6-bromo-1,2-dihydroquinoline and M 11, a 2-methyl-4-(2'-chlorophenyl)-6-bromo-quinazoline. The substitution of bromine by a hydroxyl group during the formation of M 14 can be explained by a NIH-shift mechanism. Quantitative investigations show that the methoxymethyl side chain in the benzodiazepine ring system of metaclazepam acts as an effective barrier with respect to the metabolic attack at position two. We assume that this barrier only can be overcome by complete side chain degradation. This multi-step reaction can hardly compete with more favourable and faster conjugation and elimination processes.

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Benzophenone metabolism. I. Isolation of p-hydroxybenzophenone from rat urine

Cited by 13 publications

References 6 publications

Estrogenic Activities of UV Stabilizers Used in Food Contact Plastics and Benzophenone Derivatives Tested by the Yeast Two-Hybrid Assay

Estrogenic Activities of UV Stabilizers Used in Food Contact Plastics and Benzophenone Derivatives Tested by the Yeast Two-Hybrid Assay

Estrogenic and Anti-Androgenic Activities of Benzophenones in Human Estrogen and Androgen Receptor Mediated Mammalian Reporter Gene Assays

Metabolism and pharmacokinetics of metaclazepam (Talis®), Part III: Determination of the chemical structure of metabolites in dogs, rabbits and men

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