Structure activity relations. 7. Structure-activity relations of fenamic acids

Terada, Hiroshi; Muraoka, Saburo; Fujita, Toshio

doi:10.1021/jm00249a016

Cited by 40 publications

(8 citation statements)

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“…Depending on the methods and conditions, the following different values of pK a2 were obtained i.e. : 3.85 (value determined theoretically) [31], 3.97 (capillary electrophoresis) [32], 4.91 (capillary isotachophoretic) [33], 5.0 (spectrophotometric method) [34], 5.84 (potentiometric method in the acetone (5-10%) + water system) [35], and 5.94 (potentiometric method in the ethanol (50%) + water system) [36]. The dissociation constants K a1 and K a2 are expressed by Eqs.…”

Section: Resultsmentioning

confidence: 99%

Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Zapała

2011

J Solution Chem

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In this paper, the flufenamic acid equilibria in aqueous solution and in two-phase organic solvent + aqueous solution are described and presented. The dissociation constants K a1 and K a2 were determined in MDM + water mixtures. The Yashuda-Shedlovsky extrapolation procedure has been used to obtain the values of K a1 and K a2 in aqueous solutions. The distribution ratio D was measured in the toluene + water system over a wide range of pH by the shaking flask method. Based on the results of potentiometric titrations in two-phase organic solvent (benzene, ethylbenzene, toluene, carbon tetrachloride, chloroform, chlorobenzene, and bromobenzene) + aqueous systems, and using models of single and multistep equilibria, the values of distribution constants K D and dimerization constants K dim were calculated. The influences of polarity of the applied solvents and pH of the aqueous phase, on the speciation of the particular forms of flufenamic acid in both phases, were demonstrated.

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Section: Resultsmentioning

confidence: 99%

Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Zapała

2011

J Solution Chem

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“…The first QSAR studies on this series of drugs were published by Terada and co-workers (79,80). The first QSAR studies on this series of drugs were published by Terada and co-workers (79,80).…”

Section: Anthranilic Acidsmentioning

confidence: 99%

Nonsteroidal Antiinflammatory and Antiarthritic Drugs

Gund¹,

Jensen²

1983

Medicinal Chemistry

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“…There is considerable controversy concerning the actual relationship between the acidic and gastrotoxic properties of many nonsteroidal antiinflammatory agents; however, it is generally agreed that gastric irritation is associated, directly or indirectly, with the acidic nature of these drugs. 1,2 In an effort to eliminate gastric complications, while maintaining antiinflammatory activity, a number of nonacidic compounds were evaluated for potential antiinflammatory activity.…”

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confidence: 99%

“…Isophthalonitrile (1) was catalytically chlorinated, forming tetrachloroisophthalonitrile (2). This was reacted with sodium acetate, and then hydrolyzed, to afford 4hydroxytrichloroisophthalonitrile (3).…”

mentioning

confidence: 99%

“…Utilization of excessive amine resulted in 4,6-diamination. The 4-alkoxytrichloroisophthalonitriles 5 were obtained by treatment of 2 with the appropriate alcohol and potassium fluoride. The regiospecificity of nucleophilic displacement at the 4 position of 2 by acetate, alkoxy, and amino functionalities was verified by regiospecific synthesis of the corresponding 2-hydroxyt.richloroisophthalonitrile (7, Scheme II).…”

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Synthesis and antiinflammatory evaluation of substituted isophthalonitriles and trimesonitriles, benzonitriles, and terephthalonitriles

Heilman¹,

Battershell²,

Pyne³

et al. 1978

J. Med. Chem.

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In an effort to develop nonacidic, nonsteroidal, antiinflammatory agents without gastrointestinal complications, a series of cyanobenzenes was synthesized for antiinflammatory evaluation. Twenty-seven substituted isophthalonitriles, 19 trimesonitriles, 30 benzonitriles, and 16 terephthalonitriles were tested in the rat utilizing the carrageenan-induced pedal edema assay. Based on the performance of phenylbutazone in this assay (43.8% reduction at 100 mg/kg), six compounds, dosed at 50 mg/kg, produced reductions in inflammation comparable to this standard. However, the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further the LD50 value of each compound dosed at this level was in the range of 40--56 mg/kg in the mouse; therefore, further study was not warranted. Fifteen compounds possessed activity in excess of 20% reduction at 200 mg/kg and also possessed LD50 values greater than 300 mg/kg. Of these cyanobenzenes, trimesonitrile (16), 4-chlorobenzonitrile, 2-chloroterephthalonitrile, and 2-fluoroterephthalonitrile with reductions in edema of 32, 30, 46, and 49%, respectively, represent the best candidates for subsequent study.

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Structure activity relations. 7. Structure-activity relations of fenamic acids

Cited by 40 publications

References 5 publications

Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Potentiometric Studies on the Equilibria of Flufenamic Acid in Aqueous Solutions and in Two-phase Organic Solvent + Water Systems

Nonsteroidal Antiinflammatory and Antiarthritic Drugs

Synthesis and antiinflammatory evaluation of substituted isophthalonitriles and trimesonitriles, benzonitriles, and terephthalonitriles

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