(1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan]-6'-ene-5,5'-dione

• ChemBase ID: 304
• Molecular Formular: C24H32O4S
• Molecular Mass: 416.57348
• Monoisotopic Mass: 416.2021305
• SMILES: S([C@H]1[C@H]2[C@H]3[C@@]([C@@]4(OC(=O)CC4)CC3)(CC[C@@H]2[C@@]2(C(=CC(=O)CC2)C1)C)C)C(=O)C
• Canonical SMILES: CC(=O)S[C@@H]1CC2=CC(=O)CC[C@@]2([C@@H]2[C@@H]1[C@@H]1CC[C@]3([C@]1(CC2)C)CCC(=O)O3)C
• InChI: InChI=1S/C24H32O4S/c1-14(25)29-19-13-15-12-16(26)4-8-22(15,2)17-5-9-23(3)18(21(17)19)6-10-24(23)11-7-20(27)28-24/h12,17-19,21H,4-11,13H2,1-3H3/t17-,18-,19+,21+,22-,23-,24+/m0/s1
• InChIKey: LXMSZDCAJNLERA-ZHYRCANASA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan]-6'-ene-5,5'-dione; (1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0?,?.0??,??]heptadecan]-6'-ene-5,5'-dione; (1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0^2,^7.0^1^1,^1^5]heptadecan]-6'-ene-5,5'-dione
• IUPAC Traditional name: spironolactone
• Brand Name: Abbolactone; Acelat; Aldace; Aldactazide; Aldactide; Aldactone; Aldactone A; Alderon; Aldopur; Almatol; Altex; Aquareduct; Deverol; Diatensec; Dira; Duraspiron; Espironolactona [INN-Spanish]; Euteberol; Lacalmin; Lacdene; Laractone; Melarcon; Nefurofan; Osyrol; SNL; Sagisal; Sincomen; Spiresis; Spiretic; Spiridon; Spiro-Tablinen; Spiroctan; Spiroctanie; Spiroderm; Spirolactone; Spirolakton; Spirolang; Spirolone; Spirone; Spironocompren; Spironolactone A; Spironolactone [BAN:INN:JAN]; Spironolactonum [INN-Latin]; Spironolattone [DCIT]; Sprioderm; Supra-puren; Suracton; Uractone; Urusonin; Verospiron; Verospirone; Verospirone Opianin; Xenalon
• Synonyms: Spironolactone; 4-Pregnen-21-oic acid-17α-ol-3-one-7α-thiol γ-lactone 7-acetate; 7α-(Acetylthio)-17α-hydroxy-3-oxopregn-4-ene-21-carboxylic acid γ-lactone; Spironolactone; (1'S,2R,2'R,9'R,10'R,11'S,15'S)-9'-(acetylsulfanyl)-2',15'-dimethylspiro[oxolane-2,14'-tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadecan]-6'-ene-5,5'-dione; (7α,7α)-7-(Acetylthyo)-17-hydroxy-3-oxopregn-4-one-21-carboxylic Acid γ-Lactone; 7α-Acetylthio-3-oxo-17α-pregn-4-ene-21,17-carbolactone; SC-9420; Adactone

Database IDs

• CAS Number: 52-01-7
• EC Number: 200-133-6
• MDL Number: MFCD00071615; MFCD00082250
• PubChem SID: 160963767; 24277736; 46508525
• PubChem CID: 5833
• CHEBI ID: 9241
• ATC CODE: C03DA01
• CHEMBL: 1393
• Chemspider ID: 5628
• DrugBank ID: DB00421
• IUPHAR ligand ID: 2875
• KEGG ID: D00443
• Unique Ingredient Identifier: 27O7W4T232
• Wikipedia Title: Spironolactone
• Medline Plus: a682627

CALCULATED PROPERTIES

JChem

• Acid pKa: 18.006086
• H Acceptors: 3
• H Donor: 0
• LogD (pH = 5.5): 3.6367545
• LogD (pH = 7.4): 3.6367545
• Log P: 3.6367545
• Molar Refractivity: 113.5043 cm^3
• Polarizability: 45.06745 Å^3
• Polar Surface Area: 60.44 Å^2
• Rotatable Bonds: 2
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 3.1
• LOG S: -5.32
• Solubility (Water): 1.98e-03 g/l

PROPERTIES

Physical Property

• Solubility: Chloroform; Methanol; Practically insoluble (22 mg/L)
• Apperance: White to Off White Soli-
• Melting Point: 205-207°C; 207-208 °C(lit.)
• Hydrophobicity(logP): 2.839; 3.4

Safety Information

• Storage Condition: Refrigerator; Room Temperature (15-30°C)
• RTECS: TU4725000
• European Hazard Symbols: Toxic (T); Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 60; R:22-40
• Safety Statements: 53-22-36/37/39-45; S:36/37/39
• GHS Pictograms: GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H360
• GHS Precautionary statements: P201-P308 + P313
• Personal Protective Equipment: Eyeshields, Gloves, type P2 (EN 143) respirator cartridges

Pharmacology Properties

• Admin Routes: Oral
• Excretion: Urine, bile
• Half Life: 1.3-2 hours
• Metabolism: Hepatic
• Protein Bound: 90%+
• Legal Status: POM (UK); Rx-only (US)
• Pregnancy Category: B3 (Australia); C (US)
• Gene Information: human ... HSD17B1(3292), NR3C2(4306)rat ... Ar(24208)

Product Information

• Purity: 95%; 97.0-103.0%

DETAILS

MP Biomedicals - 02190059

Crystalline Spironolactone is an aldosterone antagonist that also promotes loss of sodium through the kidney but permits retention of potassium.

DrugBank - DB00421

• Drug Groups: approved
• Description: A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p827)
• Indication: Used primarily to treat low-renin hypertension, hypokalemia, and Conn's syndrome.
• Pharmacology: Spironolactone is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics. On its own, spironolactone is only a weak diuretic, but it can be combined with other diuretics. Due to its anti-androgen effect, it can also be used to treat hirsutism, and is a common component in hormone therapy for male-to-female transgendered people. Spironolactone inhibits the effect of aldosterone by competing for intracellular aldosterone receptor in the distal tubule cells. This increases the secretion of water and sodium, while decreasing the excretion of potassium. Spironolactone has a fairly slow onset of action, taking several days to develop and similarly the effect diminishes slowly.
• Toxicity: The oral LD₅₀ of spironolactone is greater than 1,000 mg/kg in mice, rats, and rabbits. Acute overdosage of spironolactone may be manifested by drowsiness, mental confusion, maculopapular or erythematous rash, nausea, vomiting, dizziness, or diarrhea. Spironolactone has been shown to be a tumorigen in chronic toxicity studies in rats.
• Affected Organisms: Humans and other mammals
• Biotransformation: Rapidly and extensively metabolized. The metabolic pathway of spironolactone is complex and can be divided into two main routes: those in which the sulfur moiety is retained and those in which the sulfur moiety is removed by dethioacetylation. Spironolactone is transformed to a reactive metabolite that can inactivate adrenal and testicular cytochrome P450 enzymes. It also has anti-androgenic activity.
• Absorption: Fairly rapidly absorbed from the gastrointestinal tract. Food increases the bioavailability of unmetabolized spironolactone by almost 100%.
• Half Life: 10 minutes
• Protein Binding: Spironolactone and its metabolites are more than 90% bound to plasma proteins.
• Elimination: The metabolites are excreted primarily in the urine and secondarily in bile.
• References: Berardesca E, Gabba P, Ucci G, Borroni G, Rabbiosi G: Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. Int J Tissue React. 1988;10(2):115-9. [Pubmed] ; Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. [Pubmed] ; Wandelt-Freerksen E: [Aldactone in the treatment of sarcoidosis of the lungs (author's transl)] Z Erkr Atmungsorgane. 1977 Jul;149(1):156-9. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Sigma Aldrich - S3378

Biochem/physiol Actions
Spironolactone is a competitive aldosterone receptor antagonist. Used as potassium sparing diuretic.
Other Notes
Tandem Mass Spectrometry data independently generated by Scripps Center for Metabolomics is available to view or download in PDF. S3378.pdf Tested metabolites are featured on Scripps Center for Metabolomics METLIN Metabolite Database. To learn more, visit sigma.com/metlin.

Toronto Research Chemicals - S683000

It is a synthetic 17-lactone steroid which is a renal competitive aldosterone antagonist in a class of pharmaceuticals called potassium-sparing diuretics, used primarily to treat ascites in patients with liver disease, low-renin hypertension, hypokalemia

REFERENCES

• Berardesca E, Gabba P, Ucci G, Borroni G, Rabbiosi G: Topical spironolactone inhibits dihydrotestosterone receptors in human sebaceous glands: an autoradiographic study in subjects with acne vulgaris. Int J Tissue React. 1988;10(2):115-9. Pubmed
• Pitt B, Zannad F, Remme WJ, Cody R, Castaigne A, Perez A, Palensky J, Wittes J: The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N Engl J Med. 1999 Sep 2;341(10):709-17. Pubmed
• Wandelt-Freerksen E: [Aldactone in the treatment of sarcoidosis of the lungs (author's transl)] Z Erkr Atmungsorgane. 1977 Jul;149(1):156-9. Pubmed
• Sutter, J.L., et al.: Anal. Profiles Drug Subs., 4, 431 (1975)