Mespirenone

Mespirenone (INN) (developmental code name ZK-94679), also known as Δ¹-15β,16β-methylenespironolactone, is a steroidal antimineralocorticoid of the spirolactone group related to spironolactone that was never marketed.^[1][2] Animal research found that it was 3.3-fold more potent as an antimineralocorticoid relative to spironolactone.^[3] In addition to its antimineralocorticoid properties, mespirenone is also a progestogen, antigonadotropin, and antiandrogen.^[2][4] It is 2- to 3-fold as potent as spironolactone as a progestogen and antigonadotropin but its antiandrogenic activity is markedly reduced and weak (though still of significance) in comparison.^[4][5] Mespirenone is also a potent and specific enzyme inhibitor of 18-hydroxylase and thus of mineralocorticoid biosynthesis.^[6] The drug was under development by Schering (now Bayer Schering Pharma) and reached phase II clinical trials but was discontinued in 1989.^[7]

Mespirenone

Clinical data
Routes of administration	Oral
ATC code	None
Identifiers
IUPAC name S-[(4aR,4bS,6aS,7S,7aS,8aS,8bS,8cR,9R)-4a,6a-Dimethyl-2,5'-dioxo-2,4',4b,5,5',6,6a,7a,8,8a,8b,8c,9,10-tetradecahydro-3'H,4aH-spiro[cyclopropa[4,5]cyclopenta[1,2-a]phenanthrene-7,2'-furan]-9-yl] ethane thioate
CAS Number	87952-98-5
PubChem CID	65660
ChemSpider	59095
UNII	E91TME2I23
ChEMBL	ChEMBL1908314
CompTox Dashboard (EPA)	DTXSID40868989
Chemical and physical data
Formula	C25H30O4S
Molar mass	426.57 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC(=O)SC1CC2=CC(=O)C=CC2(C3C1C4C5CC5C6(C4(CC3)C)CCC(=O)O6)C
InChI InChI=InChI=1S/C25H30O4S/c1-13(26)30-19-11-14-10-15(27)4-7-23(14,2)17-5-8-24(3)22(21(17)19)16-12-18(16)25(24)9-6-20(28)29-25/h4,7,10,16-19,21-22H,5-6,8-9,11-12H2,1-3H3/t16-,17+,18+,19-,21+,22+,23+,24+,25+/m1/s1 Key:CPHJTSJQUQZOLJ-ISIDMKFXSA-N

See also

• Canrenone
• Drospirenone
• Spironolactone

References

1. Elks J (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 775–. ISBN 978-1-4757-2085-3.
2. Losert W, Bittler D, Buse M, Casals-Stenzel J, Haberey M, Laurent H, et al. (November 1986). "Mespirenone and other 15,16-methylene-17-spirolactones, a new type of steroidal aldosterone antagonists". Arzneimittel-Forschung. 36 (11): 1583–1600. PMID 3028435.
3. Weindel K, Lewicka S, Vecsei P (October 1991). "Interference of C17-spirosteroids with late steps of aldosterone biosynthesis. Structure-activity studies". Arzneimittel-Forschung. 41 (10): 1082–1091 (1083). PMID 1799390.
4. Nishino Y, Schröder H, el Etreby MF (December 1988). "Experimental studies on the endocrine side effects of new aldosterone antagonists". Arzneimittel-Forschung. 38 (12): 1800–1805. PMID 3245852.
5. Opoku J, Kalimi M, Agarwal M, Qureshi D (February 1991). "Effect of a new mineralocorticoid antagonist mespirenone on aldosterone-induced hypertension". The American Journal of Physiology. 260 (2 Pt 1): E269–E271. doi:10.1152/ajpendo.1991.260.2.E269. PMID 1996630.
6. Weindel K, Lewicka S, Vecsei P (September 1991). "Inhibitory effects of the novel anti-aldosterone compound mespirenone on adrenocortical steroidogenesis in vitro". Arzneimittel-Forschung. 41 (9): 946–949. PMID 1796922.
7. Kolkhof P, Bärfacker L, Hillisch A, Haning H, Schäfer S (8 September 2008). "Nuclear receptors as targets in cardiovascular diseases". In Ottow E, Weinmann H (eds.). Nuclear Receptors as Drug Targets. John Wiley & Sons. pp. 410–. ISBN 978-3-527-62330-3.