α,β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids, a New Class of Diuretics

Schultz, E. M.; Cragoe, Edward J.; Bicking, John B.; Bolhofer, William A.; Sprague, James M.

doi:10.1021/jm01238a030

Cited by 94 publications

(21 citation statements)

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“…Ethacrynic acid, [2,3-dichloro-4-(2-methylenebutyryl)phenoxy] acetic acid, is a diuretic which decreases sodium transport and free water clearance by the mam¬ malian renal tubule (Schultz, Cragoe, Bicking, Bolhofer & Sprague, 1962;Earley & Friedlander, 1964 ;Beyer, Baer, Michaelson & Russo, 1965). It also reduces the effects of the neurohypophysial hormone, oxytocin, and the rate of sodium transport across the toad bladder (Cobb & McManus, 1966;Marumo, Asano, Sasaoka & Koshikawa, 1967).…”

Section: Introductionmentioning

confidence: 99%

Actions of Vasopressin and Aldosterone on the Toad Bladder: Inhibition by Ethacrynic Acid

Bentley¹

1969

Journal of Endocrinology

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Ethacrynic acid inhibited short-circuit current (SCC, Na transport) across the toad bladder. Some structural analogues had similar effects and their potency varied with their ability to combine with SH groups. The Na-K ATPase inhibitor ouabain was more effective than ethacrynic acid and its action and that of ethacrynic acid was additive.The natriferic and hydro-osmotic effects of vasopressin were inhibited by ethacrynic acid (10\ m=-\ 5 and 10\m=-\4m); the antagonism was competitive at 10\m=-\and 10\m=-\4 m (but not at 10\m=-\3 m). Certain analogues of ethacrynic acid also exhibited this effect but it was not clearly related to their SH-combining ability.The natriferic and hydro-osmotic effects of caffeine and cyclic AMP were not changed by 10\m=-\4 m-ethacrynic acid.Ethacrynic acid (10\m=-\4 m), which does not affect basal sodium transport in bladders pretreated for studying the action of aldosterone, prevented the initiation of the increase in sodium transport by aldosterone but was without effect when added to a toad bladder already under the influence of aldosterone. This suggests that ethacrynic acid interferes with metabolic processes underlying the action of aldosterone. Dihydroethacrynic acid which has no SH-binding activity was without effect.

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Section: Introductionmentioning

confidence: 99%

Actions of Vasopressin and Aldosterone on the Toad Bladder: Inhibition by Ethacrynic Acid

Bentley¹

1969

Journal of Endocrinology

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“…In this case, the higher in vivo activity of the amides of TD may capitis (2), Staph. cohnii (2), Staph. simulans (2), Staph.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological properties of N63-carboxamides of teicoplanin antibiotics. Structure-activity relationships

Malabarba¹,

Trani²,

Strazzolini³

et al. 1989

J. Med. Chem.

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The condensation of the carboxyl function of teicoplanin A2 (CTA) and its acidic hydrolysis pseudoaglycons (TB, TC) and aglycon (TD) with amines carrying various functional groups and chains produced amide derivatives with different isoelectric points and lipophilicities. Amide formation did not affect the ability of these compounds to bind to Ac2-L-Lys-D-Ala-D-Ala, a model for the natural peptide binding site in bacterial cell walls. The antimicrobial activities of teicoplanin amides were found to depend mostly on their ionic and lipophilic character and on the type and number of sugars present. Positively charged amides were generally more in vitro active than the respective unmodified antibiotics against Gram-positive organisms. In particular, most basic amides of CTA were markedly more active than teicoplanin against coagulase-negative staphylococci. A few amides of TC and most of those of TD also showed a certain activity against Gram-negative bacteria. In experimental Streptococcus pyogenes septicemia in the mouse, some basic amides were more active than the parent teicoplanins when administered subcutaneously. Some of those of CTA were also slightly more effective than teicoplanin by oral route.

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“…The chemical synthesis and biological properties of ethacrynic acid and a number of its homologs and analogs are given elsewhere (1). These studies established that the a$-unsaturated aryl ketone moiety was essential for optimum biological activity.…”

mentioning

confidence: 99%

Polarographic Determination of Ethacrynic Acid

Cohen

1971

Journal of Pharmaceutical Sciences

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α,β-Unsaturated Ketone Derivatives of Aryloxyacetic Acids, a New Class of Diuretics

Cited by 94 publications

References 0 publications

Actions of Vasopressin and Aldosterone on the Toad Bladder: Inhibition by Ethacrynic Acid

Actions of Vasopressin and Aldosterone on the Toad Bladder: Inhibition by Ethacrynic Acid

Synthesis and biological properties of N63-carboxamides of teicoplanin antibiotics. Structure-activity relationships

Polarographic Determination of Ethacrynic Acid

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