(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编号: 304
• 分子式: C24H32O4S
• 平均质量: 416.57348
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: (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传统名: spironolactone
• 商标名: 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
• 别名: 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

登记号

• CAS号: 52-01-7
• EC号: 200-133-6
• MDL号: MFCD00071615; MFCD00082250
• PubChem SID: 24277736; 46508525; 160963767
• PubChem CID: 5833
• CHEBI ID: 9241
• ATC码: C03DA01
• CHEMBL: 1393
• Chemspider ID: 5628
• DrugBank ID: DB00421
• IUPHAR配体索引: 2875
• KEGG ID: D00443
• 美国药典/FDA物质标识码: 27O7W4T232
• 维基百科标题: Spironolactone
• Medline Plus: a682627

理论计算性质

JChem

• Acid pKa: 18.006086
• 质子受体: 3
• 质子供体: 0
• LogD (pH = 5.5): 3.6367545
• LogD (pH = 7.4): 3.6367545
• Log P: 3.6367545
• 摩尔折射率: 113.5043 cm^3
• 极化性: 45.06745 Å^3
• 极化表面积: 60.44 Å^2
• 可自由旋转的化学键: 2
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 3.1
• LOG S: -5.32
• 溶解度: 1.98e-03 g/l

分子性质

理化性质

• 溶解度: Chloroform; Methanol; Practically insoluble (22 mg/L)
• 外观: White to Off White Soli-
• 熔点: 205-207°C; 207-208 °C(lit.)
• 疏水性(logP): 2.839; 3.4

安全信息

• 保存条件: Refrigerator; Room Temperature (15-30°C)
• RTECS编号: TU4725000
• 欧盟危险性物质标志: 有毒(Toxic) (T); 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 60; R:22-40
• 安全公开号: 53-22-36/37/39-45; S:36/37/39
• GHS危险品标识: GHS08
• GHS警示词: Danger
• GHS危险声明: H360
• GHS警示性声明: P201-P308 + P313
• 个人保护装置: Eyeshields, Gloves, type P2 (EN 143) respirator cartridges

药理学性质

• 给药途径: Oral
• 排泄: Urine, bile
• 半衰期: 1.3-2 hours
• 代谢: Hepatic
• 蛋白结合率: 90%+
• 法定药品分级: POM (UK); Rx-only (US)
• 妊娠期药物分类: B3 (Australia); C (US)
• 相关基因信息: human ... HSD17B1(3292), NR3C2(4306)rat ... Ar(24208)

产品相关信息

• 纯度: 95%; 97.0-103.0%

详细说明

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

参考文献

• 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)