spironolactone   

GtoPdb Ligand ID: 2875

Synonyms: Aldactone® | spiractin | spirotone
spironolactone is an approved drug (FDA (1960))
Compound class: Synthetic organic
Comment: Spironolactone is an orally active, potassium-sparing diuretic, which works by antagonising the effects of aldosterone at renal mineralocorticoid receptors.
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2D Structure
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Physico-chemical Properties
Hydrogen bond acceptors 4
Hydrogen bond donors 0
Rotatable bonds 2
Topological polar surface area 85.74
Molecular weight 416.2
XLogP 3.44
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
Canonical SMILES CC(=O)SC1CC2=CC(=O)CCC2(C2C1C1CCC3(C1(CC2)C)CCC(=O)O3)C
Isomeric 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
InChI Key LXMSZDCAJNLERA-ZHYRCANASA-N
No information available.
Summary of Clinical Use
Used in the treatment of low-renin hypertension, hypokalemia and Conn's syndrome. CaroSpir® is an oral suspension of spironolactone that received US FDA approval in August 2017, developed for patients who can't swallow tablets or have difficulty swallowing. CaroSpir® is indicated for the treatment of Class III-IV heart failure (to manage edema and reduce hospitalisations), and as an adjunct to anti-hypertensive medications.
Mechanism Of Action and Pharmacodynamic Effects
Spironolactone has multiple actions including antimineralocorticoid and antiandrogenic activities, as well as estrogenic and progestogenic activities. The most relevant action is as an aldosterone antagonist at the mineralocorticoid receptor in the cortical collecting duct of renal nephrons, an action which decreases renal sodium and water reabsorption (sparing potassium excretion) to increase fluid loss. Spironolactone is also a direct androgen receptor antagonist, and this action underlies its therapeutic efficacy in androgen-dependent conditions (acne and hirsutism for example) and its utility during hormone therapy for transgender women. Activity as a weak 17β-hydroxysteroid dehydrogenase 2 inhibitor may underlie the altered testosterone:estradiol ratio and resulting gynecomastia that is associated with spironolactone administration.
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