3,3-Bisaryloxindoles as mineralocorticoid receptor antagonists

Neel, David A.; Brown, Matthew L.; Lander, Peter A.; Grese, Timothy A.; Defauw, Jean; Doti, Robert A.; Fields, Todd; Kelley, Sally Ann; Smith, Stephon C.; Zimmerman, Karen; Steinberg, Mitchell I.; Jadhav, Prabhakar K.

doi:10.1016/j.bmcl.2005.03.086

Cited by 51 publications

(16 citation statements)

References 15 publications

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“…The utility of this method was demonstrated by the concise synthesis of a spermicide agent ( a , 98%), a laxative ( d , 85%), anticancer agents ( e , 98%), and a cardiovascular drug ( f , 95%) in good to excellent yields. This finding suggests that this technique may quickly access biologically active compounds and create unique chemical libraries based on 3,3′-diarylated oxindole for screening biologically active molecules (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Lambert Salt-Initiated Development of Friedel–Crafts Reaction on Isatin to Access Distinct Derivatives of Oxindoles

et al. 2021

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Herein, a mild metal-free and efficacious route for the synthesis of biologically important 3-aryl oxindole derivatives is described. Using Lambert salt-initiated hydroarylation of isatin, a diverse array of monoarylated products, symmetrical/unsymmetrical double-arylated products, and deoxygenated hydroarylated products could be synthesized from the single starting substrate in good to excellent yields. A preliminary mechanistic study revealed that the reaction proceeds via a monoarylated product followed by a nucleophilic attack by another electron-rich arene nucleophile under mild conditions. The potential of newly synthesized symmetric/unsymmetric 3,3-disubstituted oxindole, 3-substituted 3-hydroxy oxindoles, 3,3-di(indolyl)indolin-2-ones, and α-aryl oxindoles as valuable building blocks is further illustrated.

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Section: Resultsmentioning

confidence: 99%

Lambert Salt-Initiated Development of Friedel–Crafts Reaction on Isatin to Access Distinct Derivatives of Oxindoles

et al. 2021

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“…Over the past decade, pharmaceutical companies launched drug-discovery programs for non-steroidal MRAs using various high-throughput screening methods, which has led to the identification of several drug classes which possess MRA activity [13, 16–19, 28, 29]. Review of published patent applications demonstrates that additional compounds have been identified but not yet published in the scientific literature.…”

Section: Traditional Mr Antagonistsmentioning

confidence: 99%

Is there a new dawn for selective mineralocorticoid receptor antagonism?

Luther¹

2014

Current Opinion in Nephrology and Hypertension

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Purpose of review Aldosterone and the mineralocorticoid receptor contribute to resistant hypertension and cardiovascular mortality, and mineralocorticoid receptor antagonists effectively reduce these complications. Their use is limited in certain populations with a higher risk of hyperkalemia or renal dysfunction. This review will highlight recent developments in extra-renal mineralocorticoid receptor research and the development of novel mineralocorticoid receptor antagonists. Recent findings Tissue-specific knockout-out models provide definitive evidence that vascular mineralocorticoid receptor directly contributes to hypertension and vascular remodeling, independent of renal effects. Several non-steroidal mineralocorticoid receptor antagonists are in pre-clinical development or early-stage clinical trials. Several non-steroidal MR antagonists have demonstrated preserved cardiovascular benefit with a reduced incidence of hyperkalemia in pre-clinical studies. Summary Novel, potent non-steroidal MR antagonists are in development, although their effect on cardiovascular and adverse drug events requires further investigation.

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“…This substructure is present in several potent therapeutic agents, such as the anti-cancer drug (1) 1 and cardiovascular drug (2). 2 It is also present in many natural products, including spirotryprostatine A (3) and alstonisine (4). 3 Moreover, 2-oxindoles are useful synthetic intermediates, for example in their use as precursors to the furoindoline and pyrroloindoline cores.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of functionalized 2-oxindoles by Friedel–Crafts reactions

Gasonoo

Klumpp

2015

Tetrahedron Letters

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Please cite this article as: Gasonoo, M., Klumpp, D.A., Synthesis of functionalized 2-oxindoles by Friedel-Crafts reactions, Tetrahedron Letters (2015), doi: http://dx.A series of acetonyl-substituted 3-hydroxy-2-oxindoles have been prepared and reacted with arenes in superacid promoted Friedel-Crafts reactions. The product aryl-substituted 2-oxindoles are formed in generally good yields. With substituted arenes such as toluene, bromobenzene, or anisole, the Friedel-Crafts reactions occur with excellent regioselectivity. A mechanism is proposed involving carbocationic electrophiles leading to the aromatic substitution chemistry.

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3,3-Bisaryloxindoles as mineralocorticoid receptor antagonists

Cited by 51 publications

References 15 publications

Lambert Salt-Initiated Development of Friedel–Crafts Reaction on Isatin to Access Distinct Derivatives of Oxindoles

Lambert Salt-Initiated Development of Friedel–Crafts Reaction on Isatin to Access Distinct Derivatives of Oxindoles

Is there a new dawn for selective mineralocorticoid receptor antagonism?

Synthesis of functionalized 2-oxindoles by Friedel–Crafts reactions

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