Ethenesulfonamide Derivatives, a Novel Class of Orally Active Endothelin-A Receptor Antagonists

Harada, Hironori; Kazami, Jun‐ichi; Watanuki, Susumu; Tsuzuki, Ryuji; Sudoh, Katsumi; Fujimori, A.; Tanaka, Akihiro; Tsukamoto, Shin‐ichi; Yanagisawa, Isao

doi:10.1248/cpb.49.606

Cited by 9 publications

(2 citation statements)

References 20 publications

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“…It acts as an endothelin receptor A (ET‐A) antagonist, and thereby prevents the binding of the strongly vasoconstrictive peptide hormone endothelin‐1 . A substantially improved binding affinity and selectivity for the ET‐A receptor was reported for bosentan analogue 6 , in which the arylsulfonyl moiety was replaced by a styrylsulfonyl group . With a view towards the development of antiinflammatory therapeutics, some other styrylsulfonamides and styrylsulfonates have more recently been evaluated as inhibitors of the inducible nitric oxide synthase .…”

Section: Introductionmentioning

confidence: 99%

Styrylsulfonates and ‐Sulfonamides through Pd‐Catalysed Matsuda–Heck Reactions of Vinylsulfonic Acid Derivatives and Arenediazonium Salts

2016

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Arene diazonium salts undergo Matsuda-Heck reactions with vinylsulfonates and -sulfonamides to give styrylsulfonic acid derivatives in high to excellent yields and with high to excellent selectivities. By quantifying the evolution of nitrogen over time in a gas-meter apparatus, the reactivities of ethylvinylsulfonate and the benchmark olefin methyl acrylate were compared for an electron-rich and an -deficient arene diazonium salt. Tertiary sulfonamides react in Matsuda-Heck couplings with high conversions, but require long reaction

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Section: Introductionmentioning

confidence: 99%

Styrylsulfonates and ‐Sulfonamides through Pd‐Catalysed Matsuda–Heck Reactions of Vinylsulfonic Acid Derivatives and Arenediazonium Salts

2016

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“…-Natural compounds (extracted from cultural medium of Streptomyces misakiensis or from the Chinese herb Cissus assamica) (35,77) -Etherocyclic sulfonamides (bosentan) (13) -Indane carboxylic acid derivatives (enrasentan) (50) -Dihydropyridine anhydrides (CGS 27830: meso-1,4-dihydro-5-methoxycarbonyl-2,6-dimethyl-4-(3-nitrophenyl)-3-pyridine carboxylic acid anhydride) (12) -Diarylpyrrolidine carboxylic acids (A-127722) (72) -Ethanesulfonamide derivatives (30) Enrasentan is (+)-(1S,2R,3S)-3-(2-(2-hydroxyeth-1-yloxy)-4-methoxyphenyl)-1-(3,4-methylenedioxyphenyl)-5-(prop-1-yloxy)indan-2-carboxylic acid. (Fig.…”

Section: Chemistrymentioning

confidence: 99%

Enrasentan, an Antagonist of Endothelin Receptors

Cosenzi¹

2003

Cardiovascular Drug Reviews

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Endothelins are powerful vasoconstrictor agents produced by endothelial cells and identified by Yanagisawa et al. in 1988. Two types of receptors for endothelins have been identified: ET A receptors are located on smooth muscle cells of the vascular wall and are responsible for endothelin-induced vasoconstriction while ET B receptors are located on endothelial cells and induce these cells to release NO and prostacyclin. Moreover, these peptides not only cause a potent and prolonged vasoconstriction but are also known to enhance cell proliferation and to stimulate extracellular matrix accumulation. High levels of plasma or tissue endothelins have been found in patients with heart failure, diabetes, stroke, primary pulmonary hypertension, liver cirrhosis and other diseases. Given these effects of endothelins, blocking their receptors might be a new way to reduce blood pressure and to treat other illnesses. Accordingly, many endothelin antagonists have been developed and evaluated in animals and humans. Enrasentan is a mixed ET A and ET B receptor antagonist with a higher affinity for ET A receptors, although it cannot be considered a selective antagonist. In an animal model of hypertension and cardiac hypertrophy the drug has reduced blood pressure, prevented cardiac hypertrophy and preserved myocardial function. In rats with hyperinsulinemia and hypertension enrasentan normalized blood pressure and prevented cardiac and renal damage. In rats with stroke the drug reduced the ischemic area in the brain. Enrasentan has been added to conventional treatment in patients with heart failure (NYHA Class 2-3) and no addictive effect of the drug has been observed. This is in contrast with results obtained in animal models and still has not been explained. In conclusion, many possible clinical applications can be suggested for this drug, but further studies are necessary to better evaluate its therapeutic efficacy.

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ChemInform Abstract: Ethenesulfonamide Derivatives, a Novel Class of Orally Active Endothelin‐A Receptor Antagonists.

Harada¹,

Kazami²,

Watanuki³

et al. 2001

ChemInform

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Ethenesulfonamide Derivatives, a Novel Class of Orally Active Endothelin-A Receptor Antagonists

Cited by 9 publications

References 20 publications

Styrylsulfonates and ‐Sulfonamides through Pd‐Catalysed Matsuda–Heck Reactions of Vinylsulfonic Acid Derivatives and Arenediazonium Salts

Styrylsulfonates and ‐Sulfonamides through Pd‐Catalysed Matsuda–Heck Reactions of Vinylsulfonic Acid Derivatives and Arenediazonium Salts

Enrasentan, an Antagonist of Endothelin Receptors

ChemInform Abstract: Ethenesulfonamide Derivatives, a Novel Class of Orally Active Endothelin‐A Receptor Antagonists.

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