Fasidotril: The First Dual Inhibitor of Neprilysin and ACE

Bralet, J; Marie, Christine; Gros, Claude P.; Schwartz, Jean; Lecomte, J

doi:10.1111/j.1527-3466.2000.tb00030.x

Cited by 9 publications

(4 citation statements)

References 44 publications

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“…Organosilicon compounds are essential synthetic reagents and intermediates in modern organic synthesis, and the Si atom itself is a key element in many functional materials and bioactive molecules. Particularly, chiral β-aldehydesilanes are valuable intermediates, which can be readily converted to other versatile building blocks occurring in a variety of small molecule pharmaceuticals and natural products, such as drugs A (angiotensin-converting enzyme inhibitor), B (HIV protease inhibitor) 38 , fasidotril 39 , candoxatril 40 , venlafaxine 41 , tropicamide 42 , and natural products scopolamine 43 , 44 and anisodamine 45 (Fig. 1c ).…”

Section: Introductionmentioning

confidence: 99%

Silicon-oriented regio- and enantioselective rhodium-catalyzed hydroformylation

You

Yang

et al. 2018

Nat Commun

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Hydroformylation of 1,2-disubstituted alkenes usually occurs at the α position of the directing heteroatom such as oxygen atom and nitrogen atom. By contrast, to achieve hydroformylation on the β position of the heteroatom is a tough task. Herein, we report the asymmetric rhodium-catalyzed hydroformylation of 1,2-disubstituted alkenylsilanes with excellent regioselectivity at the β position (relative to the silicon heteroatom) and enantioselectivity. In a synthetic sense, we achieve the asymmetric hydroformylation on the β position of the oxygen atom indirectly by using the silicon group as a surrogate for the hydroxyl. Density functional theory (DFT) calculations are carried out to examine energetics of the whole reaction path for Rh/YanPhos-catalyzed asymmetric hydroformylation and understand its regioselectivity and enantioselectivity. Our computational study suggests that the silicon group can activate the substrate and is critical for the regioselectivity.

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Section: Introductionmentioning

confidence: 99%

Silicon-oriented regio- and enantioselective rhodium-catalyzed hydroformylation

You

Yang

et al. 2018

Nat Commun

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“…It is the diester prodrug of the active metabolite fasidotrilat, which is protected at its two terminal parts by a thioester group on the thiol end and by a benzyl group on the carboxylic end. Fasidotril is converted in vivo to fasidotrilat by plasma and tissue esterases [104][105].…”

Section: Prodrugs Of Vasopeptidase Inhibitors (Table 5)mentioning

confidence: 99%

Prodrug Strategies for Antihypertensives

Dhaneshwar¹,

Sharma²,

Patel³

et al. 2011

CTMC

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There is a great emphasis on research to discover methods aimed at enhancing the efficacy of drugs and reducing their toxicity and unwanted side effects. Prodrugs are biologically inactive compounds that are converted to actual drug molecule, through biotransformation, that combine with the receptors to produce the biological action. Prodrugs can thus be considered as drugs containing specialized nontoxic protective groups utilized in a transient manner to alter or eliminate the undesirable properties of the parent drug molecule. Hypertension is one of the leading risk factors for cardiovascular disease and represents a major health and economic burden. Most of the drugs for cardiovascular diseases have low oral bioavailability, short duration of action, first pass metabolism and variable lipohilicities. Out of the need to overcome these limitations, various prodrugs have been designed for antihypertensive agents. This review extensively focuses on various strategies used for design and development of prodrugs for the various classes of antihypertensives, emphasizing on the details regarding the need for prodrug synthesis for each class, structure, type of modification and goal achieved. It also provides an insight into the major advances in the field of antihypertensive prodrug research.

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“…[79] Fasidotril, the first dual NEP/ACE inhibitor, has been found to be effective in various experimental models of rat hypertension, and in patients with essential hypertension. [80,81] Omapatrilat inhibits both NEP and ACE and was found to be more effective than ACE inhibitors alone. However, it has not received FDA approval due to angioedema safety concerns.…”

Section: Dual Inhibitors Of Neprilysin and Angiotensin-converting Enzymementioning

confidence: 99%

Dual inhibition: a novel promising pharmacological approach for different disease conditions

Patyar

Prakash

Medhi

2011

Journal of Pharmacy and Pharmacology

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To overcome the problems associated with polypharmacy, which include medication non compliance, adverse drug reactions, drug-drug interactions and increased pill-burden, various strategies, such as sustained-release drugs and fixed-dose combination regimens (polypills), have been developed. Out of these, a novel and very much promising approach is the use of dual-action drugs. Amongst the dual-action drugs, there is a class of compounds known as dual inhibitors, which possess the dual inhibitory activity. The most common examples of dual inhibitors are rivastigmine, ladostigil, asenapine, phenserine, amitriptyline, clomipramine, doxepin and desipramine. This review article focuses on the conventional drugs used in different diseases which possess dual inhibition activity as well as those which are still in the preclinical/clinical phase.

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Fasidotril: The First Dual Inhibitor of Neprilysin and ACE

Cited by 9 publications

References 44 publications

Silicon-oriented regio- and enantioselective rhodium-catalyzed hydroformylation

Silicon-oriented regio- and enantioselective rhodium-catalyzed hydroformylation

Prodrug Strategies for Antihypertensives

Dual inhibition: a novel promising pharmacological approach for different disease conditions

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