Chemistry:Paroxypropione

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Short description: Chemical compound
Paroxypropione
Paroxypropione.svg
Clinical data
Trade namesFrenantol, Frenormon, Hypophenon, Paroxon, Possipione, Profenone, others
Other namesParaoxypropiophenone; H-365; NSC-2834; 4'-Hydroxypropiophenone; Ethyl p-hydroxyphenyl ketone; p-Propionylphenol; Paroxypropiophenone; Parahydroxypropiophenone; PHP
Drug classNonsteroidal estrogen; Antigonadotropin
ATC code
  • None
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC9H10O2
Molar mass150.177 g·mol−1
3D model (JSmol)

Paroxypropione, also known as paraoxypropiophenone, is a synthetic nonsteroidal estrogen which has been used medically as an antigonadotropin in Spain and Italy but appears to no longer be marketed.[1][2][3][4] It was first synthesized in 1902.[1] The antigonadotropic properties of the drug were discovered in 1951[3] and it entered clinical use shortly thereafter.[5]

Pharmacology

Pharmacodynamics

Paroxypropione is closely related structurally to p-hydroxybenzoic acid and parabens such as methylparaben, and also bears a close resemblance to diethylstilbestrol (which, in fact, produces paroxypropione as an active metabolite)[6][7] and alkylphenols like nonylphenol, all of which are also estrogens.[8][9] The drug possesses relatively low affinity for the estrogen receptor[4] and must be given at high dosages to achieve significant estrogenic and antigonadotropic effects, for instance, 0.8 to 1.6 g/day.[10][11] It possesses 0.1% of the estrogenic activity and less than 0.5% of the antigonadotropic potency of estrone.[12]

Chemistry

Synthesis

The highest reported yield, approximately 96%, is from the between phenol and propionyl chloride.[13] The mechanism is likely to involve initial esterification to give phenyl propionate, which then undergoes a Fries rearrangement.

Derivatives

Paroxypropione is a precursor in the chemical synthesis of diethylstilbestrol and dienestrol.[14][15]

Society and culture

Names

Brand names Frenantol, Frenormon, Hypophenon, Paroxon, Possipione, Profenone, numerous others; former developmental code name NSC-2834), also known as paroxypropiophenone (P.O.P.) or 4'-hydroxypropiophenone.

Research

Paroxypropione was studied and used in the treatment of breast cancer.[16][17][18]

References

  1. ↑ 1.0 1.1 The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 662–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA662. 
  2. ↑ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 796–. ISBN 978-3-88763-075-1. https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA796. 
  3. ↑ 3.0 3.1 "The pituitary action and estrogenic effect of parahydroxy-propiophenone". The Journal of Clinical Endocrinology and Metabolism 11 (8): 892–4. August 1951. doi:10.1210/jcem-11-8-892. PMID 14861299. 
  4. ↑ 4.0 4.1 "Evaluation of the OECD (Q)SAR Application Toolbox for the profiling of estrogen receptor binding affinities". SAR and QSAR in Environmental Research 23 (1–2): 37–57. January 2012. doi:10.1080/1062936X.2011.623325. PMID 22014213. Bibcode: 2012SQER...23...37M. 
  5. ↑ "Fluorine-containing analogs of 4-hydroxypropiophenone". The Journal of Organic Chemistry 18 (8): 910–915. 1953. doi:10.1021/jo50014a002. ISSN 0022-3263. 
  6. ↑ Mechanism of Toxic Action on Some Target Organs: Drugs and Other Substances. Springer Science & Business Media. 12 March 2013. pp. 276–. ISBN 978-3-642-67265-1. https://books.google.com/books?id=zUH1CAAAQBAJ&pg=PA276. 
  7. ↑ "High-pressure, reverse-phase partition chromatograhy separation of diethylstilbestrol metabolites and analogs". Analytical Biochemistry 92 (1): 199–202. January 1979. doi:10.1016/0003-2697(79)90645-6. PMID 426279. 
  8. ↑ Human Reproductive Biology. Academic Press. 28 September 2013. pp. 46–. ISBN 978-0-12-382185-0. https://books.google.com/books?id=M4kEdSnS-pkC&pg=PA46. 
  9. ↑ "Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines". Journal of Applied Toxicology 25 (4): 301–9. 2005. doi:10.1002/jat.1066. PMID 16021681. 
  10. ↑ "Protein breakdown before and after operations. Influence of growth hormone and of inhibitors of the pituitary adrenal system.". Cirug., Ginecol. Urol. 9: 289–326. 1955. http://www.cabdirect.org/abstracts/19561404674.html. 
  11. ↑ "Treatment of experimental and clinical schistosomiasis with hormonal inhibitors of ovulation". The American Journal of Tropical Medicine and Hygiene 16 (4): 497–9. July 1967. doi:10.4269/ajtmh.1967.16.497. PMID 5006470. http://www.ajtmh.org/content/16/4/497.extract. [yes|permanent dead link|dead link}}]
  12. ↑ "Metabolic and toxicity studies on parahydroxypropiophenone". Endocrinology 50 (6): 607–11. June 1952. doi:10.1210/endo-50-6-607. PMID 12980070. 
  13. ↑ "Comparisons of O-acylation and Friedel–Crafts acylation of phenols and acyl chlorides and Fries rearrangement of phenyl esters in trifluoromethanesulfonicacid: effective synthesis of optically active homotyrosines". Tetrahedron 67 (3): 641–649. 2011. doi:10.1016/j.tet.2010.11.047. 
  14. ↑ William Andrew Publishing (22 October 2013). Pharmaceutical Manufacturing Encyclopedia, 3rd Edition. Elsevier. pp. 1286, 1290. ISBN 978-0-8155-1856-3. https://books.google.com/books?id=_J2ti4EkYpkC&pg=PA1286. 
  15. ↑ Organic Building Blocks of the Chemical Industry. John Wiley & Sons. 1989. pp. 532–. ISBN 978-0-471-85545-3. https://books.google.com/books?id=a2XNyj1WtkMC&pg=PA532. 
  16. ↑ "[Hydroxypropiophenone in the therapy of metastases of carcinoma of the breast]" (in it). Il Farmaco; Edizione Pratica 10 (6): 291–9. June 1955. PMID 13241536. 
  17. ↑ "P-hydroxypropiophenone for advanced breast cancer: a preliminary report". The Medical Journal of Australia 43 (5): 181–3. August 1956. doi:10.5694/j.1326-5377.1956.tb56562.x. PMID 13358357. 
  18. ↑ "[Experience with paraoxypropiophenone (Frenantol) in the treatment of dysplasias and metastasized carcinoma of the breast]" (in it). Chirurgia Italiana 19 (3): 306–12. June 1967. PMID 5188348. 

Further reading

  • "[Anti-gonadotropic action of possipione]" (in it). Quaderni di Clinica Ostetrica e Ginecologica 13 (7): 307–15. July 1958. PMID 13579130. 



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