Zanoterone

Zanoterone (INN, USAN) (former developmental code name WIN-49596), also known as (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol,[1] is a steroidal antiandrogen which was never marketed.[2][3][4] It was investigated for the treatment of benign prostatic hyperplasia (BPH) but failed to demonstrate sufficient efficacy in phase II clinical trials, and also showed an unacceptable incidence rate and severity of side effects (e.g., breast pain and gynecomastia).[4][5] As such, it was not further developed.[4][5]

Zanoterone
Clinical data
Other namesWIN-49596; (5α,17α)-1'-(methylsulfonyl)-1'-H-pregn-20-yno[3,2-c]pyrazol-17-ol
Routes of
administration		By mouth
Drug classSteroidal antiandrogen
Identifiers
IUPAC name
  • (1R,3aS,3bR,5aS,10aS,10bS,12aS)-1-ethynyl-10a,12a-dimethyl-8-(methylsulfonyl)-1,2,3,3a,3b,4,5,5a,6,8,10,10a,10b,11,12,12a-hexadecahydrocyclopenta[5,6]naphtho[1,2-f]indazol-1-ol
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC23H32N2O3S
Molar mass416.58 g·mol−1
3D model (JSmol)
SMILES
  • C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(C#C)O)CC[C@@H]4[C@@]3(CC5=CN(N=C5C4)S(=O)(=O)C)C
InChI
  • InChI=1S/C23H32N2O3S/c1-5-23(26)11-9-19-17-7-6-16-12-20-15(14-25(24-20)29(4,27)28)13-21(16,2)18(17)8-10-22(19,23)3/h1,14,16-19,26H,6-13H2,2-4H3/t16-,17+,18-,19-,21-,22-,23-/m0/s1
  • Key:MHDDZDPNIDVLNK-ZGIWMXSJSA-N

Zanoterone was derived from 5α-dihydroethisterone (5α-dihydro-17α-ethynyltestosterone).[6][7] It is an antagonist of the androgen receptor (Ki = 2.2 μM; RBA compared to metribolone = 2.2%), and with the exception of antiprogestogenic activity in rat and rabbit models, is devoid of other hormonal activities.[6][8] Zanoterone does not inhibit 5α-reductase, aromatase, or 3α- or 3β-hydroxysteroid dehydrogenase in vitro.[6] The drug significantly increases testosterone and estradiol levels in men.[9] Zanoterone has been found to not significantly inhibit mating performance or fertility in adult male rats at high dosages for an extended period of time.[6] It has been found to act as an inducer of the enzyme CYP3A4 in vivo in rats.[10]

Relative potencies of selected antiandrogens
AntiandrogenRelative potency
Bicalutamide4.3
Hydroxyflutamide3.5
Flutamide3.3
Cyproterone acetate1.0
Zanoterone0.4
Description: Relative potencies of orally administered antiandrogens in antagonizing 0.8 to 1.0 mg/kg s.c. testosterone propionate-induced ventral prostate weight increase in castrated immature male rats. Higher values mean greater potency. Sources: See template.

See also

References
  1. William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 3517–3518. ISBN 978-0-8155-1856-3.
  2. Dr. Ian Morton; I.K. Morton; Judith M. Hall (31 October 1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 294–. ISBN 978-0-7514-0499-9.
  3. C.R. Ganellin; David J. Triggle (1997). Dictionary of Pharmacological Agents. Taylor & Francis. pp. 540–. ISBN 978-0-412-46630-4.
  4. Schröder, Fritz H.; Radlmaier, Albert (2009). "Steroidal Antiandrogens". In V. Craig Jordan; Barrington J. A. Furr (eds.). Hormone Therapy in Breast and Prostate Cancer. Humana Press. pp. 325–346. doi:10.1007/978-1-59259-152-7_15. ISBN 978-1-60761-471-5.
  5. Alan J. Wein; Louis R. Kavoussi; Andrew C. Novick; Alan W. Partin; Craig A. Peters (28 September 2011). Campbell-Walsh Urology. Elsevier Health Sciences. pp. 2637–. ISBN 978-1-4557-2298-3.
  6. Annual Reports in Medicinal Chemistry. Academic Press. 8 September 1989. pp. 200–. ISBN 978-0-08-058368-6.
  7. Daniel Lednicer; Lester A. Mitscher (5 November 1998). The Organic Chemistry of Drug Synthesis. John Wiley & Sons. p. 65. ISBN 978-0-471-24510-0.
  8. Winneker RC, Wagner MM, Batzold FH (December 1989). "Studies on the mechanism of action of Win 49596: a steroidal androgen receptor antagonist". J. Steroid Biochem. 33 (6): 1133–8. doi:10.1016/0022-4731(89)90420-2. PMID 2615358.
  9. Berger, B; Naadimuthu, A; Boddy, A; Fisher, H; Mcconnell, J; Milam, D; Mobley, D; Rajfer, J (1995). "The Effect of Zanoterone, a Steroidal Androgen Receptor Antagonist, in Men with Benign Prostatic Hyperplasia". The Journal of Urology. 154 (3): 1060–1064. doi:10.1016/S0022-5347(01)66976-3. ISSN 0022-5347.
  10. Roberts, Alan E.; Ritz, Martha A.; Hoekstra, Susan; Descotes, Gerard; Hincks, Jeffrey R. (1996). "Induction of liver cytochrome P-450 (CYP) 3A in male and female rats by a steroidal androgen receptor antagonist, Zanoterone". Journal of Biochemical Toxicology. 11 (3): 101–110. doi:10.1002/(SICI)1522-7146(1996)11:3<101::AID-JBT1>3.0.CO;2-O. ISSN 0887-2082. PMID 9029268.



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