Oxidative cleavage of a tricyclic pyridone to a bicyclic lactam-dione

Friary, R.; Schwerdt, John

doi:10.1016/s0040-4020(01)96046-6

Cited by 14 publications

(27 citation statements)

References 3 publications

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“…(9)-10-(3-Chlorophenyl)-6,8,9,10-tetrahydro-6-hydroxybenzo[b] [1,8]naphthyridin-5(7H)-one (2) Preparation. Lithium tri-tert-butoxy aluminohydride (1 mL of a 1 M solution in tetrahydrofuran) was added to a stirred, cooled (ice bath) solution of 10-(3-chlorophenyl)-8,9-dihydro-benzo[b] [1,8]naphthyridin-5,6(7H, 10H)-dione [16], 6 (310 mg, 0.00095 mole) in tetrahydrofuran (6 mL) under nitrogen. The resulting red solution was allowed to stir overnight; ice was not replenished.…”

Section: Chemistrymentioning

confidence: 99%

“…This sample was identified by comparison of 1 H NMR spectra and thin-layer chromatograms with those of an authentic specimen prepared by incubation of 10-(3-chlorophenyl)-6,8,9,10-tetrahydroben- [1,8]naphthyridin-5(7H)-one, 1, with Cunninghamella echinulata (ATCC 8987) [17]. Another sample of the 6-carbinol, prepared by sodium borohydride reduction of the corresponding ketone, was also identified.…”

Section: Chemistrymentioning

confidence: 99%

“…The stereoisomers showed retention times of 4.8 and 6.0 min at 25°C. 10-(3-Chlorophenyl)-6,8,9,10-tetrahydro-9hydroxybenzo[b] [1,8]…”

Section: Chemistrymentioning

confidence: 99%

“…It cannot be titrated with normal hydrochloric acid. Leaving this nitrogen atom unaffected, even two equivalents of 3-chloroperbenzoic acid oxidize the drug exclusively at the D 5a,9a double bond within the pyridone [8]. The pyridone oxygen atom of 40120, not its pyridine nitrogen atom, forms a hydrogen bond [9].…”

Section: Introductionmentioning

confidence: 99%

“…

The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10- (3chlorophenyl)-6,8,9,10-tetrahydrobenzol[b] [1,8]naphthyridin-5(7H)-one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol.

…”

mentioning

confidence: 99%

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In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites

Zbáida¹,

Du²,

Shannon³

et al. 1998

Biopharm. Drug Dispos.

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The metabolism of SCH 40120, which is the clinically effective antipsoriatic drug 10‐(3‐chlorophenyl)‐6,8,9,10‐tetrahydrobenzol[b][1,8]naphthyridin‐5(7H)‐one, was determined in vitro. Rat, dog, cynomolgus monkey, and human liver slices hydroxylated the aliphatic, cyclohexenyl ring of the drug and conjugated the resulting carbinol. The identified metabolites comprised the corresponding 6‐, 7‐, and 9‐carbinols, the glucuronide of the 6‐carbinol, and the 6‐ketone derived from the parent drug. Although the three carbinols appeared in the liver isolates of all species studied, the relative amounts of these metabolites varied across species. With a high, non‐physiological ratio of substrate to liver, the 6‐carbinol and its glucuronide were the major metabolites in human and monkey, whereas the 6‐ketone was a minor metabolite in dog. Containing a stereogenic axis and center, the 6‐carbinol existed as diastereomeric atropisomers. Its structure was established by 13C and 1H NMR spectroscopy, mass spectrometry, and comparison to an authentic sample. © 1998 John Wiley & Sons, Ltd.

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Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

“…The stereoisomers showed retention times of 4.8 and 6.0 min at 25°C. 10-(3-Chlorophenyl)-6,8,9,10-tetrahydro-9hydroxybenzo[b] [1,8]…”

Section: Chemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

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In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites

Zbáida¹,

Du²,

Shannon³

et al. 1998

Biopharm. Drug Dispos.

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ChemInform Abstract: Oxidative Cleavage of a Tricyclic Pyridone to a Bicyclic Lactam‐dione.

Friary

Schwerdt

1992

ChemInform

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Oxidation reactions of dibenzothiophene subjected to negative chemical ionization with oxygen

Drabner

Budzikiewicz

1993

J. Am. Soc. Mass Spectrom.

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Dibenzothiophene (1) suffers surface-catalyzed oxidation under CI(O2) conditions. While in the positive mode M(+) is the only major ion and those of the oxidation products are of minor importance in the negative mode, essentially only ions stemming from oxidized species can be seen, the sulfone ion [M+O2](-) being the most important one. The ion m/z 184 previously attributed to M(-) is actually the anion of 2-sulfobenzoic acid cyclic anhydride. Structures for the various oxidation products are proposed and the mechanisms leading to their formation are discussed.

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Oxidative cleavage of a tricyclic pyridone to a bicyclic lactam-dione

Cited by 14 publications

References 3 publications

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites

In vitro metabolism of 10-(3-chlorophenyl)-6,8,9,10-tetrahydrobenzo[b][1,8]naphthyridin-5(7H)-one, a topical antipsoriatic agent. Use of precision-cut rat, dog, monkey and human liver slices, and chemical synthesis of metabolites

ChemInform Abstract: Oxidative Cleavage of a Tricyclic Pyridone to a Bicyclic Lactam‐dione.

Oxidation reactions of dibenzothiophene subjected to negative chemical ionization with oxygen

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