Canrenone

Names

[ CAS No. ]:
976-71-6

[ Name ]:
Canrenone

[Synonym ]:
Phanurane
Luvion
ALDADIENE
(17a)-17-Hydroxy-3-oxopregna-4,6-diene-21-carboxylic acid g-lactone
17a-(2-Carboxyethyl)-17b-hydroxyandrosta-4,6-dien-3-one Lactone
Canrenone
Spiro[17H-cyclopenta[a]phenanthrene-17,2'(5'H)-furan]-3,5'(2H)-dione, 1,3',4',8,9,10,11,12,13,14,15,16-dodecahydro-10,13-dimethyl-, (8R,9S,10R,13S,14S,17R)-
17a-(2-Carboxyethyl)-17b-hydroxy-3-oxoandrosta-4,6-diene Lactone
3-(3-Oxo-17b-hydroxy-4,6-androstadien-17a-yl)propionic Acid g-Lactone
Contaren
6-Dehydrotestosterone-17a-propionic Acid g-Lactone
CANRENONE-D4
(8R,9S,10R,13S,14S,17R)-10,13-Dimethyl-1,8,9,10,11,12,13,14,15,16-decahydro-3'H-spiro[cyclopenta[a]phenanthrene-17,2'-furan]-3,5'(2H,4'H)-dione
11614 R.P.

Biological Activity

[Description]:

Canrenone (Aldadiene; SC9376; SC14266) is an aldosterone antagonist extensively used as a diuretic agent.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Mineralocorticoid Receptor

Research Areas >> Cardiovascular Disease

[Target]

Target: Aldosterone[1]

[In Vitro]

Canrenone inhibits the production of eortieosterone, 18-hydroxydesoxyeortieosterone, 18-hydroxycorticosterone and aldosterone in a dose-dependent manner[1]. Canrenone dose-dependently reduces platelet-derived growth factor–induced cell proliferation and motility. Canrenone inhibits the activity of the Na+/H+ exchanger 1 induced by platelet-derived growth factor[2].

[In Vivo]

Canrenone is the principal active metabolite of Spironolactone in the rat only for a limited period. During chronic treatment a difference developed between the effect of Spironolactone and Canrenone on the RAAS indicating a decrease in the anti-mineralocorticoid activity of Canrenone and an increase in the efficacy of Spironolactone[3].

[Cell Assay]

Confluent Hepatic Stellate Cells (HSC) are incubated in SFIF medium for 24 hours and exposed to increasing concentrations of canrenone (1, 5, 10, 25 μM). Cell viability is evaluated by the trypan blue dye exclusion test at the end of a 24- to 48-hour incubation period[2].

[Animal admin]

Rats[3] Canrenone (CAN) is given orally in two different doses (10.25, 20.5 mg/mL) to Male SPF Sprague-Dawley rats for 6 weeks. To determine the Na+, K+, fluid and aldosterone excretion the urine of the rats destined to be killed after 6 weeks is collected at weekly intervals[3].

[References]

[1]. Erbler HC, et al. On the mechanism of the inhibitory action of the spirolactone SC 9376 (aldadiene) on the production of corticosteroids in rat adrenals in vitro. Naunyn Schmiedebergs Arch Pharmacol. 1973;277(2):139-49.

[2]. Caligiuri A, et al. Antifibrogenic effects of canrenone, an antialdosteronic drug, on human hepatic stellate cells. Gastroenterology. 2003 Feb;124(2):504-20.

[3]. Erbler HC, et al. Effect of spironolactone and its main metabolite canrenone on the renin-angiotensin-aldosterone-system during long-term treatment in rats. Acta Endocrinol (Copenh). 1979 Jan;90(1):147-56.

[Related Small Molecules]

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
541.1±50.0 °C at 760 mmHg

[ Melting Point ]:
158-160ºC

[ Molecular Formula ]:
C₂₂H₂₈O₃

[ Molecular Weight ]:
340.456

[ Flash Point ]:
237.6±30.2 °C

[ Exact Mass ]:
340.203857

[ PSA ]:
43.37000

[ LogP ]:
2.99

[ Vapour Pressure ]:
0.0±1.4 mmHg at 25°C

[ Index of Refraction ]:
1.581

MSDS

Click to get detail MSDS

Toxicological Information

CHEMICAL IDENTIFICATION

RTECS NUMBER :: TU3493000

CHEMICAL NAME :: Pregna-4,6-diene-21-carboxylic acid, 17-hydroxy-3-oxo-, gamma-lactone, (17-alpha)-

CAS REGISTRY NUMBER :: 976-71-6

BEILSTEIN REFERENCE NO. :: 0046602

LAST UPDATED :: 199612

DATA ITEMS CITED :: 1

MOLECULAR FORMULA :: C22-H28-O3

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :: LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :: Oral

SPECIES OBSERVED :: Rodent - rat

DOSE/DURATION :: >5 gm/kg

TOXIC EFFECTS :: Details of toxic effects not reported other than lethal dose value

REFERENCE :: ATDAEI Acute Toxicity Data. Journal of the American College of Toxicology, Part B. (Mary Ann Liebert, Inc., 1651 Third Ave., New York, NY 10128) V.1- 1990- Volume(issue)/page/year: 1,36,1990

Safety Information

[ Symbol ]:

GHS08, GHS09

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H351-H411

[ Precautionary Statements ]:
P280

[ Hazard Codes ]:
Xn,N

[ Risk Phrases ]:
40-51/53

[ Safety Phrases ]:
36/37-61

[ RIDADR ]:
UN 3077 9 / PGIII

[ HS Code ]:
29329990

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Aldosterone receptor blockers spironolactone and canrenone: two multivalent drugs.

Expert Opin. Pharmacother. 15(7) , 909-12, (2014)

Canrenone is a derivative of spironolactone with lower antiandrogen activity. The drug is used only in few countries and can block all the side effects of aldosterone (ALDO). The drug is effective eve...

Additional use of an aldosterone antagonist in patients with mild to moderate chronic heart failure: a systematic review and meta-analysis.

Br. J. Clin. Pharmacol. 75(5) , 1202-12, (2013)

Aldosterone antagonists (AldoAs) have been used to treat severe chronic heart failure (CHF). There is uncertainty regarding the efficacy of using AldoAs in mild to moderate CHF with New York Heart Ass...

The effects of canrenone on inflammatory markers in patients with metabolic syndrome.

Ann. Med. 47(1) , 47-52, (2015)

To evaluate the effects of canrenone compared to placebo on blood pressure control, some non-conventional biomarkers in cardiovascular stratification, and on metalloproteinases in patients affected by...