7α-Thiospironolactone
Chemical compound / From Wikipedia, the free encyclopedia
7α-Thiospironolactone (7α-TS; developmental code name SC-24813; also known as deacetylspironolactone) is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and a minor active metabolite of spironolactone.[1][2] Other important metabolites of spironolactone include 7α-thiomethylspironolactone (7α-TMS; SC-26519), 6β-hydroxy-7α-thiomethylspironolactone (6β-OH-7α-TMS), and canrenone (SC-9376).[1][2][3][4]
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Other names | 7α-TS; SC-24813; Deacetylspironolactone; Mercaptospironolactone; 17α-Hydroxy-7α-mercapto-3-oxopregn-4-ene-21-carboxylic acid γ-lactone |
Drug class | Antimineralocorticoid; Antiandrogen |
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Formula | C22H30O3S |
Molar mass | 374.54 g·mol−1 |
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Spironolactone is a prodrug with a short terminal half-life of 1.4 hours.[5][6][7] The active metabolites of spironolactone have extended terminal half-lives of 13.8 hours for 7α-TMS, 15.0 hours for 6β-OH-7α-TMS, and 16.5 hours for canrenone, and accordingly, these metabolites are responsible for the therapeutic effects of the drug.[5][6]
7α-TS and 7α-TMS have been found to possess approximately equivalent affinity for the rat ventral prostate androgen receptor (AR) relative to that of spironolactone.[8] The affinity of 7α-TS, 7α-TMS, and spironolactone for the rat prostate AR is about 3.0 to 8.5% of that of dihydrotestosterone (DHT).[8]
7α-TS, via a reactive metabolite formed by 17α-hydroxylase, is a suicide inhibitor of 17α-hydroxylase, and is thought to be involved in the inhibition of 17α-hydroxylase by spironolactone.[9][10][11]
Compound | Cmax (ng/mL) (day 1) | Cmax (ng/mL) (day 15) | AUC (ng•hr/ml) (day 15) | t1/2 (hr) |
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Spironolactone | 72 | 80 | 231 | 1.4 |
Canrenone | 155 | 181 | 2173 | 16.5 |
7α-TMSTooltip 7α-Thiomethylspironolactone | 359 | 391 | 2804 | 13.8 |
6β-OH-7α-TMSTooltip 6β-Hydroxy-7α-thiomethylspironolactone | 101 | 125 | 1727 | 15.0 |
A study assessed the interaction of spironolactone and 7α-TS with sex hormone-binding globulin and found that they had very low affinity for this carrier protein.[13]