Synthesis and antiinflammatoy activities of .alpha.-methylfluorene-2-acetic acid and related compounds

Stiller, Eric T.; Diassi, Patrick A.; Gerschutz, Daniel; Meikle, Diane; Moetz, James R.; Principe, Pacifico A.; Levine, Seymour D.

doi:10.1021/jm00280a009

Cited by 36 publications

(8 citation statements)

References 4 publications

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“…All HPLC analyses were carried out under these conditions unless specified otherwise. (2-Fluoreny1)acetic acid (I, C2A-FL), mp 184-185 "C, was prepared by acylating fluorene with ethyl oxalyl chloride followed by Wolff-Kishner reduction according to the procedure of Stiller et al (1972).…”

Section: Methodsmentioning

confidence: 99%

Design, synthesis, and fluorescence studies of fluorenyl fatty acids as new depth-dependent fluorescent probes for membranes: getting over the looping-back problem

Lala

Dixit²,

Koppaka³

et al. 1988

Biochemistry

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Fluorescent fatty acids have proved very useful in studying the membrane hydrophobic core. They readily partition into membranes or can be converted to phospholipids, which form integral components of membranes. By attaching the fluorescent chromophore to different positions along the alkyl chain of fatty acids, e.g., an anthroyloxy group attached via an ester linkage to n-hydroxystearic acid, membranes have been probed at different depths. While this is an interesting approach and has been extensively used, relatively little attention has been paid to the molecular design of these probes in order to have minimal membrane perturbation. In the present study we have looked into the general problem of design of such depth-dependent membrane probes. We report here a series of fluorenyl fatty acids with varying fatty acid chain lengths, Le., (2-fluoreny1)acetic acid, -butyric acid, -hexanoic acid, and -octanoic acid, in order to obtain information at different depths in the membrane hydrophobic core. To see the effect of attachment of a hydrophobic tail on the orientation of such fatty acids in membranes, an n-butyl group was linked to the C-7 position of fluorene in (2-fluoreny1)butyric acid to get 4-(7-n-butylfluoren-2-yl)butyric acid. Further, to assess their ability to act as depth-dependent fluorescent probes, these fatty acids were incorporated in vesicles prepared from egg phosphatidylcholine, and their fluorescence quenching was studied with potassium iodide, Cu(II), 9,lO-dibromostearic acid, and 12-bromostearic acid. The Stern-Volmer plots so obtained clearly indicated the following depth order: 8-(2-fluorenyl)octanoic acid > 6-(2-fluorenyl)hexanoic acid > 4-(7-n-butylfluoren-2-yl)butyric acid > 4-(2-fluorenyl)butyric acid > (2-fluoreny1)acetic acid. These results indicate that the fluorenyl fatty acids reported here do probe the membrane at different depths, depending on their transverse location. In addition, the attachment of a hydrophobic tail helps in better aligning the probe in membranes and could thus overcome the problems associated with looping back of such fatty acids to the membrane-water interface. These results were also supported by fluorescence polarization data. The general design strategy utilized here can in principle be extended to other membrane probes like photoactivatable fatty acids.

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Section: Methodsmentioning

confidence: 99%

Design, synthesis, and fluorescence studies of fluorenyl fatty acids as new depth-dependent fluorescent probes for membranes: getting over the looping-back problem

Lala

Dixit²,

Koppaka³

et al. 1988

Biochemistry

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“…For example, verapamil ( 1 ) is used clinically for the treatment of chronic obstructive pulmonary disease and hypertension. As synthetic intermediates, α-aryl nitriles are potentially valuable precursors for the synthesis of well-known drugs such as indoprofen ( 2 ), cicloprofen ( 3 ), and naproxen ( 4 ) as shown in Figure . Furthermore, α-aryl nitriles are also versatile building blocks for constructing the corresponding amides, aldehydes, ketones, primary amines, and heterocycles .…”

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confidence: 99%

Facile Preparation of α-Aryl Nitriles by Direct Cyanation of Alcohols with TMSCN Under the Catalysis of InX₃

Chen

Wang

et al. 2008

Org. Lett.

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“…17 Traditionally a-hydroxy acids can be prepared via the corresponding cyanohydrins using hydrogen cyanide 18 and Grignard reagent. 19 However, the need to use highly toxic cyanides makes this process less attractive and somewhat troublesome from the point of view of industry, particularly for the production of pharmaceuticals, which are for human consumption. Alternatively, the a-hydroxy acids can be prepared via electrocarboxylation of the corresponding methyl aryl ketones with a mercury cathode in a divided cell.…”

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confidence: 99%

Facile Synthesis of α-Hydroxy-α-Methyl Carboxylic Acids by Electrochemical Carboxylation of Methyl Aryl Ketones

Janmanchi¹,

Mohan²,

Reddy³

2002

Synthesis

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Electrochemical carboxylation of methyl aryl ketones in the presence of atmospheric pressure of carbon dioxide using platinum cathode and dissolved magnesium anode at constant current density of 10 mA/cm 2 gave the corresponding a-hydroxy-a-methyl carboxylic acids in 79-84% isolated yields. The precursor of cicloprofen, a-hydroxy-a-methylfluorene-2-acetic acid (1a) and biprofen, a-hydroxy-a-methybiphenyl-4-acetic acid (2a) were readily obtained in good yield by a similar electrochemical carboxylation of 2-acetylfluorene (1) and 4-acetylbiphenyl (2). Cyclic voltammetric studies showed that the reaction is reversible indicating the preferential generation of stable anion radicals from methyl aryl ketones and that further addition of carbon dioxide does not take place in these electrochemical carboxylations.

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Synthesis and antiinflammatoy activities of .alpha.-methylfluorene-2-acetic acid and related compounds

Abstract: Table 111 Jiggle-cage effect,a Jigglecage effect,a Dosage range effect,@ Compd dose, mg/kg sc dose, w l k g PO dose, mg/kg PO 10 11 12 13 19 16 14 15

Cited by 36 publications

References 4 publications

Design, synthesis, and fluorescence studies of fluorenyl fatty acids as new depth-dependent fluorescent probes for membranes: getting over the looping-back problem

Design, synthesis, and fluorescence studies of fluorenyl fatty acids as new depth-dependent fluorescent probes for membranes: getting over the looping-back problem

Facile Preparation of α-Aryl Nitriles by Direct Cyanation of Alcohols with TMSCN Under the Catalysis of InX₃

Facile Synthesis of α-Hydroxy-α-Methyl Carboxylic Acids by Electrochemical Carboxylation of Methyl Aryl Ketones

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Synthesis and antiinflammatoy activities of .alpha.-methylfluorene-2-acetic acid and related compounds

Abstract: Table 111 Jiggle-cage effect,a Jigglecage effect,a Dosage range effect,@ Compd dose, mg/kg sc dose, w l k g PO dose, mg/kg PO 10 11 12 13 19 16 14 15

Cited by 36 publications

References 4 publications

Design, synthesis, and fluorescence studies of fluorenyl fatty acids as new depth-dependent fluorescent probes for membranes: getting over the looping-back problem

Design, synthesis, and fluorescence studies of fluorenyl fatty acids as new depth-dependent fluorescent probes for membranes: getting over the looping-back problem

Facile Preparation of α-Aryl Nitriles by Direct Cyanation of Alcohols with TMSCN Under the Catalysis of InX3

Facile Synthesis of α-Hydroxy-α-Methyl Carboxylic Acids by Electrochemical Carboxylation of Methyl Aryl Ketones

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Facile Preparation of α-Aryl Nitriles by Direct Cyanation of Alcohols with TMSCN Under the Catalysis of InX₃