107724-20-9 Usage
Description
Eplerenone, also known as 9,11α-epoxy-17α-hydroxy-3-oxopregn-4-ene-7α,21-dicarboxylic acid, γ-lactone, methyl ester (Inspra), is a selective aldosterone receptor antagonist (SARA) that belongs to the class of mineralocorticoid receptor antagonists. It is structurally similar to Spironolactone and is used for the treatment of hypertension. Eplerenone works by blocking the action of aldosterone, a natural substance in the body that raises blood pressure.
Uses
Used in Pharmaceutical Industry:
Eplerenone is used as an antihypertensive agent for the treatment of high blood pressure. It is used alone or in combination with other medications to manage hypertension by blocking the action of aldosterone.
Used in Cardiology:
Eplerenone is used as an adjunct in the management of chronic heart failure. It is similar to the diuretic spironolactone but may be more specific for the mineralocorticoid receptor, making it a preferred choice in certain cases.
Used in Oncology:
Eplerenone is also used as an anticancer agent, exhibiting potential benefits in cancer treatment.
Chemical Properties:
Eplerenone is an odorless, white to off-white crystalline powder. It is very slightly soluble in water, with its solubility being essentially pH-independent. The octanol/water partition coefficient of eplerenone is approximately 7.1 at pH 7.0.
Brand Name:
Inspra (Searle) is the brand name under which Eplerenone is marketed.
Pharmacodynamics
Eplerenone, an aldosterone receptor antagonist similar to spironolactone, has been shown to produce sustained increases in plasma renin and serum aldosterone, consistent with inhibition of the negative regulatory feedback of aldosterone on renin secretion. The resulting increased plasma renin activity and aldosterone circulating levels do not overcome the effects of eplerenone. Eplerenone selectively binds to recombinant human mineralocorticoid receptors relative to its binding to recombinant human glucocorticoid, progesterone and androgen receptors.
Biological activity
Eplerenone belongs to a class of drugs called aldosterone antagonists. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.
Eplerenone works by interfering with the activity of a steroid in your body called aldosterone. Aldosterone acts to increase the amount of sodium and water you retain. This increased sodium and water can cause high blood pressure, which can in turn cause heart failure.
Interactions
Eplerenone is primarily metabolized by the cytochrome P450 enzyme CYP3A4. Thus the potential exists for adverse drug interactions with other drugs that induce or inhibit CYP3A4. Specifically, the concomitant use of the CYP3A4 potent inhibitors ketoconazole and itraconazole is contraindicated. Other CYP3A4 inhibitors including erythromycin, saquinavir, and verapamil should be used with caution. Other drugs that increase potassium concentrations may increase the risk of hyperkalemia associated with eplerenone therapy, including salt substitutes, potassium supplements and other potassium-sparing diuretics.
Mechanism of action
Aldosterone,with many physiological and pathological effects, can cause central blood pressure and endothelial injury (catecholamines enhance its role), reduce heart rate variability, induce ventricular arrhythmias, and promote retention of sodium, potassium and magnesium loss, promote myocardial fibrosis, necrosis and inflammation, damage the fibrinolytic system.
Angiotensin converting enzyme inhibitors (also called angiotensin converting enzyme inhibitors, referred to as ACEI) and angiotensin Ⅱ receptor antagonist ARB aldosterone can inhibit the secretion of adrenaline, but after a period of treatment.The release of aldosterone was restored,which may even exceed the baseline plasma concentration levels. Despite adequate treatment of ACEI and ARB, aldosterone-induced damage can still happen, so it is necessary to use aldosterone receptor antagonists in the treatment of hypertension. Clinical studies have shown that patients who are not satisfied with the efficacy of ACEI or ARB therapy can add eplerenone along with the treatment.
Non-selective aldosterone receptor antagonist spironolactone can reduce mortality in patients with congestive heart failure, However, the side effects of male hyperplasia and other diseases associated with sex hormones have limited its application in the treatment of hypertension.
Adverse effects
Common adverse drug reactions (ADRs) associated with the use of eplerenone include: hyperkalaemia, hypotension, dizziness, altered renal function, and increased creatinine concentration.
References
https://en.wikipedia.org/wiki/Eplerenone
https://medlineplus.gov/druginfo/meds/a603004.html
http://www.rxlist.com/inspra-drug.htm
Originator
Ciba-Geigy (Novartis) (US)
Biological Activity
Selective mineralocorticoid (aldosterone) receptor antagonist (IC 50 = 360 nM). Displays > 27-fold selectivity over androgen, progesterone and estrogen receptors (IC 50 > 10 μ M). Orally active antihypertensive in vivo .
Biochem/physiol Actions
Eplerenone is an aldosterone antagonist more specific for the mineralocorticoid receptor than spironolactone (S3378), having lower affinity for progesterone, androgen, and glucocorticoid receptors.
Clinical Use
A newer drug, eplerenone, has a structure similar to that of spironolactone and a similar mechanism of action. It was initially approved for use in the treatment of
hypertension but it can now be used in the treatment of patients with left ventricular systolic dysfunction and congestive heart failure after myocardial infarction.
Drug interactions
Potentially hazardous interactions with other drugsACE inhibitors or AT-II antagonists: enhanced
hypotensive effect; risk of severe hyperkalaemia.Anti-arrhythmics: concentration increased by
amiodarone - reduce eplerenone dose.amiodarone - reduce eplerenone dose.
Antibacterials: concentration increased by
clarithromycin and telithromycin - avoid;
concentration increased by erythromycin - reduce
eplerenone dose; concentration reduced by rifampicin
- avoid; avoid with lymecycline; increased risk of
hyperkalaemia with trimethoprim.Antidepressants: concentration reduced by St John’s
wort - avoid; increased risk of postural hypotension
with tricyclics; enhanced hypotensive effect with
MAOIs.Antiepileptics: concentration reduced by
carbamazepine, fosphenytoin, phenytoin,
phenobarbital and primidone - avoid.Antifungals: concentration increased by itraconazole
and ketoconazole - avoid; concentration increased by
fluconazole - reduce eplerenone dose.Antihypertensives: enhanced hypotensive effect,
increased risk of first dose hypotensive effect with
post-synaptic alpha-blockers.Antivirals: concentration increased by ritonavir -
avoid; concentration increased by saquinavir - reduce
eplerenone doseCiclosporin: increased risk of hyperkalaemia and
nephrotoxicityCytotoxics: increased risk of nephrotoxicity and
ototoxicity with platinum compounds.NSAIDs: increased risk of hyperkalaemia (especially
with indometacin); increased risk of nephrotoxicity;
antagonism of diuretic effect.Potassium salts: increased risk of hyperkalaemia.Lithium: reduced lithium excretion - avoidTacrolimus: increased risk of hyperkalaemia and
nephrotoxicity.CYP3A4 inhibitors: Do not exceed a dose of 25 mg
daily for eplerenone.CYP3A4 inducers: reduced eplerenone
concentration - avoid.
Metabolism
Eplerenone metabolism is primarily mediated via
CYP3A4. No active metabolites of eplerenone have
been identified in human plasma. Less than 5% of
an eplerenone dose is recovered as unchanged drug
in the urine and faeces. Following a single oral dose
of radiolabelled drug, approximately 32% of the dose
was excreted in the faeces and approximately 67% was
excreted in the urine
Check Digit Verification of cas no
The CAS Registry Mumber 107724-20-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,0,7,7,2 and 4 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 107724-20:
(8*1)+(7*0)+(6*7)+(5*7)+(4*2)+(3*4)+(2*2)+(1*0)=109
109 % 10 = 9
So 107724-20-9 is a valid CAS Registry Number.
InChI:InChI=1/C24H30O6/c1-21-7-4-14(25)10-13(21)11-15(20(27)28-3)19-16-5-8-23(9-6-18(26)30-23)22(16,2)12-17-24(19,21)29-17/h10,15-17,19H,4-9,11-12H2,1-3H3/t15-,16+,17-,19+,21+,22+,23-,24-/m1/s1
107724-20-9Relevant articles and documents
A diastereoselective synthesis of 7α-nitromethyl steroid derivative and its use for an efficient synthesis of eplerenone
Zhang, Bin,Chen, Hongli,Tang, Huanyu,Feng, Huijin,Li, Yuanchao
, p. 1086 - 1091 (2012)
A novel and efficient method of stereoselectively introducing α-nitromethyl group to C-7 position of 11α-hydroxyl canrenone 4 was described. In addition, this method was successfully applied in a total synthesis of Eplerenone 8. The route was characteristic of simple operation, moderate reaction conditions with 5 steps and 55% total yield, at the same time, without any expensive or toxic reagent in use.
Preparation method of eplerenone with high efficiency and low pollution
-
, (2020/11/10)
The invention discloses a preparation method of eplerenone with high efficiency and low pollution, and belongs to the technical field of preparation and processing of steroid hormone drugs. The methodcomprises the steps: by taking a compound I, namely delta 9,11-canrenone, as an initial raw material, carrying out 7-furyl addition, furyl ring opening and lactonization cyclization reaction to obtain 5,7-lactone, and carrying out ring opening methylation and 9,11-double bond epoxidation reaction to obtain the eplerenone. According to the method, raw materials and reagents are cheap and easy to obtain, and the method has extremely high market competitiveness in equipment investment and production cost; reagents used in the method are low in environmental pollution, and particularly cyano-containing high-toxicity compounds are not used, so that the method is greener and more environment-friendly; the production process is easy to control, high in yield, low in cost and suitable for industrial production.
A steroid compound derivative having, its preparation process and its use in the preparation of Eplerenone
-
, (2020/05/05)
The invention relates to a canrenone derivative steroid compound, a preparation method and an application in the medicine field, and particularly relates to 7alpha-nitro methyl-11alpha,17beta-dihydroxy-3-oxo-17alpha-pregna-4-ene-21-carboxylic acid-gamma-lactone (a compound shown in formula 2), a preparation method and an application in eplerenone preparation. The key steps of the invention are that nitromethane is used as a nucleophilic reagent; the alpha-nitro methyl group is introduced to the C-7 position stereoselectively so as to further construct a carboxylic acid methyl ester structure with a C-7alpha position configuration of eplerenone; the method of the invention has the characteristics of short steps, mild conditions, and low cost.