3-(R)-[3-(2-Methoxyphenylthio-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5-benzoxathiepine Bromhydrate (F 15845) Prevents Ischemia-Induced Heart Remodeling by Reduction of the Intracellular Na+ Overload

Vié, Bruno; Sablayrolles, Sylvie; Létienne, Robert; Vacher, Bernard; Darmellah, Amaria; Bernard, Monique; Feuvray, D.; Grand, Bruno Le

doi:10.1124/jpet.109.153122

Cited by 15 publications

(3 citation statements)

References 45 publications

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“…The combined blockade of peripheral nociceptive signaling pathways, such as the Anti-ischemic in vivo models; myocardial infarction acute model [364][365][366][367] Pyrazines 2010 Na v 1.8 Spinal nerve ligation model of neuropathic pain [252] Isoxazoles 2009 Na v 1.7 Spinal nerve ligation model of neuropathic pain [242] Isoxazolines [289] [a] Preclinical small molecules claimed to have inhibitory activity against a given Na v 1.X subtypes for which bibliographic information could not be retrieved: Neu-P12 (Na v 1.7/Na v 1.3), [368] CR4892 (Na v 1.8). One potential strategy of differentiation from these highly brain-penetrant compounds could be envisaged in the avoidance of the CNS-mediated side effects by means of a peripheral compound.…”

Section: Individual Subtypes As Drug Targetsmentioning

confidence: 99%

“…In vivo F15845 2010 Na v 1.5 Anti-ischemic in vivo models; myocardial infarction acute model [364][365][366][367] Pyrazines 2010 Na v 1.8 Spinal nerve ligation model of neuropathic pain [252] Isoxazoles 2009 Na v 1.7 Spinal nerve ligation model of neuropathic pain [242] Isoxazolines 2009 Na v 1.7 Complete Freund's adjuvant model of inflammatory pain [246] BZP 2009 Na v 1.7 Complete Freund's adjuvant model of inflammatory pain; spinal nerve ligation model of neuropathic pain [289] [a] Preclinical small molecules claimed to have inhibitory activity against a given Na v 1.X subtypes for which bibliographic information could not be retrieved: Neu-P12 (Na v 1.7/Na v 1.3), [368] CR4892 (Na v 1.8). [369] ChemMedChem [370] Purdue Pharma 2012 Na v 1.7 WO 2012035421 [371] Novartis AG 2012 Na v 1.7 WO 2012035023 [372] Gilead Sciences Inc. 2012 Na v 1.2 WO 2012003392 [286] RaQualia Pharma Inc. 2012 Na v 1.3, Na v 1.7 WO 2012020567 [373] Pfizer Ltd. 2012 Na v 1.7 WO 2012007868 [374] Purdue Pharma 2012 Nav1.7 WO 2012007836 [375] Pfizer Ltd. 2012 Na v 1.7 WO 2012007877 [376] Pfizer Ltd. 2012 Na v 1.7 WO 2012007869 [377] Icagen Inc./Pfizer Ltd. 2012 Na v 1.7 WO 2012004714 [378] Icagen Inc./Pfizer Ltd. 2012 Na v 1.7 WO 2012004706 [379] Vertex Pharmaceuticals Inc. 2011 Na v 1.7 WO 2011140425 [380] [381] University College London 2011 Na v 1.6 WO2011061469 [287] GlaxoSmithKline plc.…”

Section: In Vitromentioning

confidence: 99%

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Advances in Targeting Voltage‐Gated Sodium Channels with Small Molecules

Nardi¹,

Damann²,

Hertrampf³

et al. 2012

ChemMedChem

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Blockade of voltage-gated sodium channels (VGSCs) has been used successfully in the clinic to enable control of pathological firing patterns that occur in conditions as diverse as chronic pain, epilepsy, and arrhythmias. Herein we review the state of the art in marketed sodium channel inhibitors, including a brief compendium of their binding sites and of the cellular and molecular biology of sodium channels. Despite the preferential action of this drug class toward over-excited cells, which significantly limits potential undesired side effects on other cells, the need to develop a second generation of sodium channel inhibitors to overcome their critical clinical shortcomings is apparent. Current approaches in drug discovery to deliver novel and truly innovative sodium channel inhibitors is next presented by surveying the most recent medicinal chemistry breakthroughs in the field of small molecules and developments in automated patch-clamp platforms. Various strategies aimed at identifying small molecules that target either particular isoforms of sodium channels involved in specific diseases or anomalous sodium channel currents, irrespective of the isoform by which they have been generated, are critically discussed and revised.

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Section: Individual Subtypes As Drug Targetsmentioning

confidence: 99%

Section: In Vitromentioning

confidence: 99%

Advances in Targeting Voltage‐Gated Sodium Channels with Small Molecules

Nardi¹,

Damann²,

Hertrampf³

et al. 2012

ChemMedChem

View full text Add to dashboard Cite

show abstract

“…F15845 has been shown to selectively inhibit the persistent sodium current of Nav1.5 exerting cardioprotective effects following ischemia. [ 67 ] In vitro testing showed minimal effects of F15845 on other important ion channels of the heart, including major Ca 2+ and K + channels. [ 68 ] This characteristic is thought to account for the limited effect of F15845 to change other heart parameters, such as basal cardiac function, hemodynamic functions, and VF.…”

Section: Ion Channel Blockersmentioning

confidence: 99%

Linked biaromatic compounds as cardioprotective agents

Mokrov

2021

Archiv der Pharmazie

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Cardiovascular diseases (CVDs) are widespread in the modern world, and their number is constantly growing. For a long time, CVDs have been the leading cause of morbidity and mortality worldwide. Drugs for the treatment of CVD have been developed almost since the beginning of the 20th century, and a large number of effective cardioprotective agents of various classes have been created. Nevertheless, the need for the design and development of new safe drugs for the treatment of CVD remains. Literature data indicate that a huge number of cardioprotective agents of various generations and mechanisms correspond to a single generalized pharmacophore model containing two aromatic nuclei linked by a linear linker. In this regard, we put forward a concept for the design of a new generation of cardioprotective agents with a multitarget mechanism of action within the indicated pharmacophore model. This review is devoted to a generalization of the currently known compounds with cardioprotective properties and corresponding to the pharmacophore model of biaromatic compounds linked by a linear linker. Particular attention is paid to the history of the creation of these drugs, approaches to their design, and analysis of the structure-action relationship within each class.

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The late sodium current in heart failure: pathophysiology and clinical relevance

Horváth

Bers

2014

ESC Heart Failure

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Large and growing body of data suggest that an increased late sodium current (I Na,late ) can have a significant pathophysiological role in heart failure and other heart diseases. The first goal of this article is to describe how I Na,late functions under physiological circumstances. The second goal is to show the wide range of cellular mechanisms that can increase I Na,late in cardiac disease, and also to describe how the up-regulated I Na,late contributes to the pathophysiology of heart failure. The final section of the article discusses the possible use of I Na,late -modifying drugs in heart failure, on the basis of experimental and preclinical data.

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3-(R)-[3-(2-Methoxyphenylthio-2-(S)-methylpropyl]amino-3,4-dihydro-2H-1,5-benzoxathiepine Bromhydrate (F 15845) Prevents Ischemia-Induced Heart Remodeling by Reduction of the Intracellular Na⁺ Overload

Cited by 15 publications

References 45 publications

Advances in Targeting Voltage‐Gated Sodium Channels with Small Molecules

Advances in Targeting Voltage‐Gated Sodium Channels with Small Molecules

Linked biaromatic compounds as cardioprotective agents

The late sodium current in heart failure: pathophysiology and clinical relevance

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