Spirolactones are a class of functional group in
organic chemistry
Organic chemistry is a subdiscipline within chemistry involving the scientific study of the structure, properties, and reactions of organic compounds and organic materials, i.e., matter in its various forms that contain carbon atoms.Clayden, ...
featuring a cyclic ester attached
spiro to another ring system. The name is also used to refer to a class of synthetic
steroids, called steroid-17α-spirolactones, 17α-spirolactosteroids, or simply 17α-spirolactones, which feature their spirolactone group at the C17α position.
They are
antimineralocorticoid
An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic drug which antagonizes the action of aldosterone at mineralocorticoid receptors. This group of drugs is ofte ...
s, or
antagonists of the
mineralocorticoid receptor
The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...
(which is activated predominantly by the
mineralocorticoid
Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances ( electrolyte balance and fluid balance). The primary ...
steroid hormone
A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...
aldosterone), and have been employed clinically as
potassium-sparing diuretic
Potassium-sparing diuretics refers to drugs that cause diuresis without causing potassium loss in the urine. They are typically used as an adjunct in management of hypertension, cirrhosis, and congestive heart failure. The steroidal aldostero ...
s.
Some also possess
progestogenic and/or
antiandrogen
Antiandrogens, also known as androgen antagonists or testosterone blockers, are a class of drugs that prevent androgens like testosterone and dihydrotestosterone (DHT) from mediating their biological effects in the body. They act by blocking the ...
properties, which have both contributed to
side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequence ...
s and been utilized for medical indications (e.g.,
spironolactone
Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...
as an antiandrogen, and
drospirenone
Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination wi ...
as a progestin).
The spirolactones were developed by
G. D. Searle & Company in the 1950s and thereafter and were denoted as "SC" compounds (e.g., SC-9420 for spironolactone).
The spirolactones include the marketed drugs
spironolactone
Spironolactone, sold under the brand name Aldactone among others, is a medication that is primarily used to treat fluid build-up due to heart failure, liver scarring, or kidney disease. It is also used in the treatment of high blood press ...
(SC-9420; Aldactone),
canrenone
Canrenone, sold under the brand names Contaren, Luvion, Phanurane, and Spiroletan, is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone which is used as a diuretic in Europe, including in Italy and Belgium. It ...
(SC-9376; Cantaren, Luvion),
potassium canrenoate
Potassium canrenoate ( INN, JAN) or canrenoate potassium (USAN) (brand names Venactone, Soldactone), also known as aldadiene kalium, the potassium salt of canrenoic acid, is an aldosterone antagonist of the spirolactone group. Like spironolact ...
(SC-14266; Venactone, Soldactone),
eplerenone
Eplerenone, sold under the brand name Inspra, is an aldosterone antagonist type of potassium-sparing diuretic that is used to treat chronic heart failure and high blood pressure, particularly for patients with resistant hypertension due to ele ...
(SC-66110, CGP-30083; Inspra), and
drospirenone
Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses. It is available both alone under the brand name Slynd and in combination wi ...
(ZK-30595; Yasmin). Spirolactones that were not ever marketed include
SC-5233
SC-5233, also known as 6,7-dihydrocanrenone or 20-spirox-4-ene-3,20-dione, is a synthetic, steroidal antimineralocorticoid of the spirolactone group which was developed by G. D. Searle & Company in the 1950s but was never marketed. It was the fi ...
,
SC-8109
SC-8109 is a steroidal antimineralocorticoid of the spirolactone group which was never marketed. It is a potent antagonist of the mineralocorticoid receptor and is more potent than the related drug SC-5233 (of which SC-8109 is the 19-nor analog ...
,
SC-11927 (Catatoxic Steroid 1; CS-1),
spiroxasone
Spiroxasone (, ) is a synthetic, steroidal antimineralocorticoid of the spirolactone group which was developed as a diuretic and antihypertensive agent but was never marketed. It was synthesized and assayed in 1963. The drug is 7α-acetylthi ...
,
prorenone
Prorenone (developmental code name SC-23133) is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed. It is the lactonic form of prorenoic acid (prorenoate), and prorenoate potassium (S ...
(SC-23133),
prorenoate potassium
Prorenoate potassium (developmental code name SC-23992) is a synthetic steroidal antimineralocorticoid
An antimineralocorticoid, also known as a mineralocorticoid receptor antagonist (MRA or MCRA) or aldosterone antagonist, is a diuretic dru ...
(SC-23992),
7α-thiospironolactone
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. Other import ...
(SC-24813),
mexrenone
Mexrenone (code names ZK-32055, SC-25152) is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed. It is the lactonic form of mexrenoic acid (mexrenoate), and mexrenoate potassium (SC-2 ...
(SC-25152, ZK-32055),
dicirenone
Dicirenone (International Nonproprietary Name, INN, United States Adopted Name, USAN; developmental code name SC-26304; also known as 7α-carboxyisopropylspirolactone) is a synthetic compound, synthetic, steroidal antimineralocorticoid of the spi ...
(SC-26304),
7α-thiomethylspironolactone
7α-Thiomethylspironolactone (7α-TMS; developmental code name SC-26519) is a steroidal antimineralocorticoid and antiandrogen of the spirolactone group and the major active metabolite of spironolactone. Other important metabolites of spironola ...
(SC-26519),
mexrenoate potassium
Mexrenoate potassium (developmental code name SC-26714) is a synthetic steroidal antimineralocorticoid which was never marketed.
See also
* Mexrenoic acid
* Mexrenone
Mexrenone (code names ZK-32055, SC-25152) is a steroidal antimineraloco ...
(SC-26714),
spirorenone
Spirorenone (INN) (developmental code name ZK-35973) is a steroidal antimineralocorticoid of the spirolactone group that was never marketed. Spirorenone possesses 5–8 times the antimineralocorticoid activity of spironolactone in animal studies ...
(ZK-35973),
ZK-91587 (15β,16β-methylenemexrenone),
mespirenone (ZK-94679), and
ZK-97894 (7α-thiomethylmespirenone).
Oxprenoate potassium
Oxprenoate potassium (developmental code name RU-28318) is a synthetic steroidal antimineralocorticoid which was never marketed. The affinities of oxprenoate potassium for the steroid hormone receptor
Steroid hormone receptors are found in th ...
(RU-28318) is not a spirolactone by definition but is a closely related antimineralocorticoid that was never marketed.
SC-5233 (6,7-dihydrocanrenone), the C17α
propanoic acid
Propionic acid (, from the Greek words πρῶτος : ''prōtos'', meaning "first", and πίων : ''píōn'', meaning "fat"; also known as propanoic acid) is a naturally occurring carboxylic acid with chemical formula CH3CH2CO2H. It is a liqu ...
lactone
Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring.
Lactones are formed by intramolecular esterification of the co ...
of
testosterone
Testosterone is the primary sex hormone and anabolic steroid in males. In humans, testosterone plays a key role in the development of male reproductive tissues such as testes and prostate, as well as promoting secondary sexual characteristi ...
(androst-4-en-17β-ol-3-one), is the unsubstituted
parent
A parent is a caregiver of the offspring in their own species. In humans, a parent is the caretaker of a child (where "child" refers to offspring, not necessarily age). A ''biological parent'' is a person whose gamete resulted in a child, a male t ...
or
prototype compound of the spirolactones, and is one of a few of the simplest members of the series along with SC-8109 (the 19-demethyl analogue of SC-5233) and canrenone (the 1,2-didehydro analogue of SC-5233).
Spironolactone is a derivative of SC-5233 with a 7α-acetylthio group (that is, SC-5233 is 7α-desthioacetylspironolactone).
See also
*
7α-Thioprogesterone (SC-8365)
References
Antimineralocorticoids
Lactones
Pregnanes
Spiro compounds
Spirolactones
Spironolactone
{{Steroid-stub