Über Ringschlussreaktionen von 3,3′‐Methylen‐bis‐(4‐hydroxycumarinen)

Litvan, F.; Stoll, W. G.

doi:10.1002/hlca.19590420332

Cited by 8 publications

(4 citation statements)

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“…Having examined positional isomerism, it was next of interest to study effects of variation in the chemical structure of the central linker. Since the "horizontal" dimer is more potent than the "vertical" dimer (compounds 8 and 9, respectively, Table 1), the former pattern was utilized, and a series of aryl-containing geminal coumarins (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27) was prepared (Table 3). Using as a reference compound 8, which has an unsubstituted benzyl central linker, addition of hydroxyl (compounds 13 and 14) or amino (compound 15) functionality to the 4-position reduced inhibitory activity approximately 3-4-fold, while either nitro or carboxyl substituents at this position had little effect (compounds 16 and 17, respectively).…”

Section: Resultsmentioning

confidence: 99%

Coumarin-Based Inhibitors of HIV Integrase

et al. 1997

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The structures of a large number of HIV-1 integrase inhibitors have in common two aryl units separated by a central linker. Frequently at least one of these aryl moieties must contain 1,2-dihydroxy substituents in order to exhibit high inhibitory potency. The ability of o-dihydroxy-containing species to undergo in situ oxidation to reactive quinones presents a potential limitation to the utility of such compounds. The recent report of tetrameric 4-hydroxycoumarin-derived inhibitor 5 provided a lead example of an inhibitor which does not contain the catechol moiety. Compound 5 represents a large, highly complex yet symmetrical molecule. It was the purpose of the present study to determine the critical components of 5 and if possible to simplify its structure while maintaining potency. In the present study, dissection of tetrameric 5 (IC50 = 1.5 microM) into its constituent parts showed that the minimum active pharmacophore consisted of a coumarin dimer containing an aryl substituent on the central linker methylene. However, in the simplest case in which the central linker aryl unit consisted of a phenyl ring (compound 8, IC50 = 43 microM), a significant reduction in potency resulted by removing two of the original four coumarin units. Replacement of this central phenyl ring by more extended aromatic systems having higher lipophilicity improved potency, as did the addition of 7-hydroxy substituents to the coumarin rings. Combining these latter two modifications resulted in compounds such as 3,3'-(2-naphthalenomethylene)bis[4,7-dihydroxycoumarin] (34, IC50 = 4.2 microM) which exhibited nearly the full potency of the parent tetramer 5 yet were structurally much simpler.

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Section: Resultsmentioning

confidence: 99%

Coumarin-Based Inhibitors of HIV Integrase

et al. 1997

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“…The possible fragmentation pathways are proposed in Schemes 7 and 8. [26][27][28][29][30][31]. Interaction between 3-methoxy-2-hydroxybenzaldehyde and 4-hydroxycoumarin in a molar ratio of 1:2 at reflux gave 3-(2Ј-hydroxy-5Ј-bromobenzylidene)diketochromane 4 d. The structure of these compounds was confirmed by mass-spectral analysis.The compound 4 d exhibits a different mass-spectral behaviour in comparison to the known coumarin derivatives.…”

Section: Methodsmentioning

confidence: 99%

“…Reaction between 2-hydroxy-3-methoxybenzaldehyde and 4-hydroxycoumarin in a molar ratio 1:2 at reflux gave 3-[6-oxo-(1H)-11-methoxybenzopyrano [4,3-b]benzopyran-7-yl]-4-hydroxy-2H-1-benzopyran-2-one 4 c [26][27][28][29][30][31]. Interaction between 3-methoxy-2-hydroxybenzaldehyde and 4-hydroxycoumarin in a molar ratio of 1:2 at reflux gave 3-(2Ј-hydroxy-5Ј-bromobenzylidene)diketochromane 4 d. The structure of these compounds was confirmed by mass-spectral analysis.The compound 4 d exhibits a different mass-spectral behaviour in comparison to the known coumarin derivatives.…”

Section: Tablementioning

confidence: 99%

Synthesis and Pharmacological Investigations of Some 4‐Hydroxycoumarin Derivatives

Manolov¹,

Danchev²

2003

Archiv der Pharmazie

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The synthesis of ten coumarin derivatives of 4-hydroxycoumarin and various unsaturated ketones and aldehydes is described. The structures of the synthesized compounds were confirmed by IR, (1)H-NMR, and mass-spectral data. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effects of the derivatives with respect to warfarin, showed that the compounds have anticoagulant activity. Compounds 4-hydroxy-3-[1-phenyl-2-(4'-chlorobenzoyl)ethyl]-2H-1-benzopyran-2-one 2b, 4-hydroxy-3-[1-(4-fluorophenyl)-3-oxobutyl]-2H-1-benzopyran-2-one 3a, and 3, 3'-p-bromobenzylidene-bis-(4-hydroxy-2H-1-benzopyran-2-one) 4b showed slight acute toxicity and a greater anticoagulant effect than warfarin.

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“…For the synthesis of 1, Litvan and Stoll [6] performed a condensation between 4-hydroxycoumarin and either 2,6-dichlorobenzaldehyde or 2-chloro-6-nitrobenzaldehyde. Eckstein et al [7] synthesized 1 by reaction of 4-hydroxycoumarin and 2-bromobenzaldehyde (2 : 1) in the presence of sodium acetate in glacial acetic acid.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticoagulant Activities of Substituted 2,4‐Diketochromans, Biscoumarins, and Chromanocoumarins

Manolov¹,

Maichle‐Moessmer

Nicolova

et al. 2006

Archiv der Pharmazie

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Different substituted 2,4-diketochromans, biscoumarins, and chromanocoumarins are the final products when 4-hydroxycoumarin and aromatic aldehydes containing hydroxyl group in o-, m,- or p-position condense in boiling ethanol. We synthesized 14 compounds. Three of them are described for the first time. The X-ray crystal structure analysis of 3-[6-oxo-(6H, 7H)-benzopyrano[4,3-b]benzopyran-7-yl]-4-hydroxy-2H-1-benzopyran-2-one 1 confirmed the structure of this compound. Acute toxicity studies of the compounds were performed on mice by oral and intraperitoneal administration. A comparative pharmacological study of the in vivo anticoagulant effect of the derivatives with respect to warfarin showed that the synthesized compounds have different anticoagulant activities. The most prospective compounds are 3-(3'-hydroxybenzylidene)-2,4-diketochroman 4 and 3,3'-(2-pyridylmethylene)-bis-4-hydroxy-2H-1-benzopyran-2-one 11 with low toxicity and dose-dependent anticoagulant activity in vivo.

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Über Ringschlussreaktionen von 3,3′‐Methylen‐bis‐(4‐hydroxycumarinen)

Cited by 8 publications

References 1 publication

Coumarin-Based Inhibitors of HIV Integrase

Coumarin-Based Inhibitors of HIV Integrase

Synthesis and Pharmacological Investigations of Some 4‐Hydroxycoumarin Derivatives

Synthesis and Anticoagulant Activities of Substituted 2,4‐Diketochromans, Biscoumarins, and Chromanocoumarins

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