Aminobenzoic acid diuretics. 3. 4-Substituted 5-sulfamylanthranilic acid derivatives

Feit, Peter W.; Nielsen, O. B. T.

doi:10.1021/jm00271a021

Cited by 12 publications

(3 citation statements)

References 4 publications

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“…The crude thiol (166 or 167, 5 mmol) was dissolved in stirred saturated NaHCOs (12-15 ml) followed by addition of NaHCOs (1.0 g, 12 mmol) and, in small portions, Na2S204 (1.0 g. 6 mmol). The appropriate alkyl iodide or alkyl bromide, for 178 4-chloromethylpyridine and for 179 4-vinylpyridine (6)(7)(8)(9)(10) mmol), was added, and the mixture was stirred at room tempera-ture for 2-4 hr. In the case of 178, 180, and 181 the reaction time, was extended to 18-20 hr and in the case of 169, 170, 172, 173, and 179 the reaction was performed at 65-70°for 3-4 hr.…”

Section: Table Iii) Methodsmentioning

confidence: 99%

Aminobenzoic acid diuretics. 7. 3-Substituted 4-phenyl-, 4-arylcarbonyl-, and 4-arylmethyl-5-sulfamoylbenzoic acids and related compounds

Nielsen¹,

Bruun²,

Bretting³

et al. 1975

J. Med. Chem.

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Various 4-substituted 3-alkylamino-, 3-alkoxy-, 3-alkylthio-, and 3-alkyl-5-sulfamoylbenzoic acids related to known aminobenzoic acid diuretics were synthesized and screened for their diuretic properties in dogs. The tabulated results from a 3-hr test period revealed that generally the diuretic profile and potency could be retained when 3-alkoxy, 3-alkylthio, and 3-phenethyl were substituted for the 3-alkylamino moiety. The high potency of several 3-alkoxy-, 3-alkylthio-, and 3-phenethyl-4-benzoyl-5-sulfamoylbenzoic acids confirmed previous suggestions that the apparent diuretic effect of 4- and 5-alkylamino-6-carboxy-3-phenyl-1,2-benzisothiazole 1,1-dioxides originates from the corresponding 4-benzoyl-5-sulfamoylbenzoic acid derivatives due to an existing equilibrium in plasma. 4-Benzoyl-5-sulfamoyl-3-(3-thenyloxy) benzoic acid (118) is among the most potent benzoic acid diuretics hitherto synthesized and shows significant diuretic activity in dogs at 1 mug/kg. The results obtained with different 3-substituted 4-phenyl-5-sulfamoylbenzoic acids supported the earlier concept regarding the steric influence of the 4-substituent on the diuretic potency of sulfamoylbenzoic acid diuretics.

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Section: Table Iii) Methodsmentioning

confidence: 99%

Aminobenzoic acid diuretics. 7. 3-Substituted 4-phenyl-, 4-arylcarbonyl-, and 4-arylmethyl-5-sulfamoylbenzoic acids and related compounds

Nielsen¹,

Bruun²,

Bretting³

et al. 1975

J. Med. Chem.

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“…Bumetanide is a metanilamide derivative with potent diuretic activity (Feit, 1971) and therapeutic efficacy broadly similar to that of frusemide (Brogden, Speight & Avery, 1975;Drug and Therapeutics Bulletin, 1974;Lancet, 1975). From the results of comparative studies in healthy subjects and patients (Asbury, Gatenby, O'Sullivan & Bourke, 1972;Olesen, Sigurd, Steiness & Leth, 1973;Davies, Lant, Millard, Smith, Ward & Wilson, 1974;Murdoch & Auld, 1975) its potency relative to frusemide has been accepted as 40:1 in clinical practice (Drug and Therapeutics Bulletin, 1974;Lancet, 1975).…”

Section: Introductionmentioning

confidence: 99%

Bumetanide and frusemide: a comparison of dose‐response curves in healthy men.

Ramsay¹,

McInnes²,

Hettiarachchi³

et al. 1978

Brit J Clinical Pharma

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I Log dose-responses for the loop d *etics bumetanide and frusemide in healthy subjects deviated significantly from parallelism as reg ds urine volume and sodium excretion. Ignoring the nonparallelism the best estimate of natriuretic potency (bumetanide: frusemide) was 46: 1 in the bumetanide dose range 0.5-2 mg. 2 For a given natriuresis the urinary potassium excretion following bumetanide was significantly lower than that for frusemide within this dose range. 3 The data illustrate the limitations of studies comparing diuretics at a single dose level. Extrapolation of the observed log dose-response curves provides one possible explanation for the relative potency (bumetanide: frusemide) of 20: 1 reported when the drugs are used at high dosage in patients with renal failure.

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“…2-Chloro-4-phenoxy-5-sulfamylbenzamide (7). A mixt of ichloro-4-phenoxy-5-sulfamylbenzoic acid7 (6) (5.0 g) and SOG, (10 ml) was refluxed for 1 hr.…”

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confidence: 99%

Structure-activity studies on sulfamyl diuretics

Feit¹,

Nielsen²,

Bruun³

1972

J. Med. Chem.

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54 g, 0.39 mole), anhyd Me2CO (400 g, 6.9 moles), and NaOH (100 g, 2.5 moles) at such a rate {ca. 1 hr) to maintain gentle reflux. The reaction mixt was then refluxed for an addl 4 hr and coned under reduced pressure. After addn of H20 (600 ml) the mixt was passed through a filter while hot, the filtrate cooled, acidified (HC1), and extd (CHQ3). The ext was purified by treatment with decolorizing C. After evapn of the solvent the residue was taken up in 2 A NaOH, the soln treated with activated C and, subsequently, acidified with dil HQ. On cooling a solid formed that was filtered off, washed (cold H20), dried,and recrystd from CC14 to give 36 g (40%) of product, mp 123-124°. Anal. (C10HnNOs) C, , N, O.Ethyl 2-(4-Aminophenoxy)-2-methylpropionate HC1 Salt (IV).A mixt of 2-(4-nitrophenoxy>2-methylpropionic acid (14 g, 0.062 mole), 10% Pd/C (1 g), and 10 ml of coned HQ in 100 ml of EtOH was shaken under H2 until the uptake of gas ceased {ca. 3 hr). After filtration the solvent was evapd under reduced pressure. The wet residue was dissolved in EtOH-PhH. After evapn of the azeotropic mixt, 14.3 g (99%) of cryst 2-(4-aminophenoxy)-2methylpropionic acid• HC1 was obtained. This product (14.3 g, 0.062 mole), without further purification, was dissolved in 200 ml of abs EtOH. Dry HQ was passed through the soln which was then heated under reflux for 1 hr, coned to 25 ml, and cooled. Addn of 200 ml of Et20 caused pptn of a white cryst material which was collected on a filter, washed (Et20), and dried. Crude material (13.4 g, 83%) (mp 159-163°) was obtd. A sample was recrystd from MeCN, mp 163-165°. Anal. (C12H1SC1N03) C, H, Cl, N, O.Ethyl 2-{4-[A,A-Bis(2-hydroxyethyl)amino] phenoxy}-2methylpropionate (V). To the crude ester IV (11.4 g, 0.044 mole) in 100 ml of H20 was added 5 g of NaHC03, 80 ml of glac AcOH, and 10 ml of EtOH. The soln was cooled to -5°, 30 ml of liq ethylene oxide added, and the mixt allowed to stand at room temp for 4 days. The mixt was then neutralized with

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Aminobenzoic acid diuretics. 3. 4-Substituted 5-sulfamylanthranilic acid derivatives

Cited by 12 publications

References 4 publications

Aminobenzoic acid diuretics. 7. 3-Substituted 4-phenyl-, 4-arylcarbonyl-, and 4-arylmethyl-5-sulfamoylbenzoic acids and related compounds

Aminobenzoic acid diuretics. 7. 3-Substituted 4-phenyl-, 4-arylcarbonyl-, and 4-arylmethyl-5-sulfamoylbenzoic acids and related compounds

Bumetanide and frusemide: a comparison of dose‐response curves in healthy men.

Structure-activity studies on sulfamyl diuretics

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