Paroxypropione

Paroxypropione
Clinical data
Trade names Frenantol, Frenormon, Hypophenon, Paroxon, Possipione, Profenone, others
Synonyms NSC-2834; 4'-Hydroxypropiophenone; Ethyl p-hydroxyphenyl ketone; p-Propionylphenol; Paroxypropiophenone; Parahydroxypropiophenone; PHP
Drug class Nonsteroidal estrogen; Antigonadotropin
ATC code
  • None
Legal status
Legal status
  • In general: ℞ (Prescription only)
Identifiers
CAS Number
PubChem CID
ChemSpider
ECHA InfoCard 100.000.676 Edit this at Wikidata
Chemical and physical data
Formula C9H10O2
Molar mass 150.175 g/mol
3D model (JSmol)

Paroxypropione 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]

Similarly to p-hydroxybenzoic acid,[13] paroxypropione has been found to possess antioxidant activity.[14]

Chemistry

Synthesis

In the best case, a ~96% yield was reported from the reaction between phenol and propionyl chloride.[15] The mechanism is likely to involve initial ester formation, followed by a Fries rearrangement.

Derivatives

Paroxypropione is a precursor in the chemical synthesis of:

  1. Nonsteroidal stilbestrol estrogens including diethylstilbestrol, dienestrol and hexestrol
  2. Fenalcomine
  3. Buphenine which itself is a precursor to bufeniode
  4. Isoxsuprine
  5. Ractopamine
  6. Fenprodil and traxoprodil
  7. A patent for para-hydroxy-phenylpropanolamine was also disclosed[16]
  8. DE547174 describes the synthesis of oxilofrine

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.

References

  1. 1 2 J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 662–. ISBN 978-1-4757-2085-3.
  2. ↑ Index Nominum 2000: International Drug Directory. Taylor & Francis. January 2000. pp. 796–. ISBN 978-3-88763-075-1.
  3. 1 2 Paulsen, C. Alvin; Mortimore, Glenn E.; Heller, Carl G. (1951). "THE PITUITARY ACTION AND ESTROGENIC EFFECT OF PARAHYDROXYPROPIOPHENONE". The Journal of Clinical Endocrinology & Metabolism. 11 (8): 892–894. doi:10.1210/jcem-11-8-892. ISSN 0021-972X.
  4. 1 2 Mombelli, E. (2012). "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. doi:10.1080/1062936X.2011.623325. ISSN 1062-936X.
  5. ↑ Buu-Hoi, Ng. Ph.; Xuong, Ng. D.; Lavit, Denise (1953). "Fluorine-containing analogs of 4-hydroxypropiophenone". The Journal of Organic Chemistry. 18 (8): 910–915. doi:10.1021/jo50014a002. ISSN 0022-3263.
  6. ↑ P.L. Chambers; P. Günzel (12 March 2013). Mechanism of Toxic Action on Some Target Organs: Drugs and Other Substances. Springer Science & Business Media. pp. 276–. ISBN 978-3-642-67265-1.
  7. ↑ Gottschlich, Regina; Metzler, Manfred (1979). "High-pressure, reverse-phase partition chromatography separation of diethylstilbestrol metabolites and analogs". Analytical Biochemistry. 92 (1): 199–202. doi:10.1016/0003-2697(79)90645-6. ISSN 0003-2697.
  8. ↑ Richard E. Jones; Kristin H. Lopez (28 September 2013). Human Reproductive Biology. Academic Press. pp. 46–. ISBN 978-0-12-382185-0.
  9. ↑ Pugazhendhi D, Pope GS, Darbre PD (2005). "Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines". J Appl Toxicol. 25 (4): 301–9. doi:10.1002/jat.1066. PMID 16021681.
  10. ↑ De Vega Ruiz, T (1955). "Protein breakdown before and after operations. Influence of growth hormone and of inhibitors of the pituitary adrenal system". Cirug., Ginecol. Urol. 9: 289–326.
  11. ↑ Bussolati C, de Carneri I, Castellino S, Marinoni V, Sperzani GL (1967). "Treatment of Experimental and Clinical Schistosomiasis with Hormonal Inhibitors of Ovulation". Am. J. Trop. Med. Hyg. 16 (4): 497–9. PMID 5006470.
  12. ↑ Scott, Charles C.; Kroc, Robert L.; Stasilli, Neil R. (1952). "METABOLIC AND TOXICITY STUDIES ON PARA-HYDROXYPROPIOPHENONE". Endocrinology. 50 (6): 607–611. doi:10.1210/endo-50-6-607. ISSN 0013-7227.
  13. ↑ Vafiadis, Anastasios P.; Bakalbassis, Evangelos G. (2003). "A computational study of the structure-activity relationships of some p-hydroxybenzoic acid antioxidants". Journal of the American Oil Chemists' Society. 80 (12): 1217–1223. doi:10.1007/s11746-003-0845-3. ISSN 0003-021X.
  14. ↑ Kiresee Saghana, PR; Hemalatha, S. "Free Radical Scavenging Activity of 4-Hydroxypropiophenone by In Vitro Assays" (PDF). World Journal of Pharmacy and Pharmaceutical Sciences. 4 (12): 935–950. ISSN 2278-4357.
  15. ↑ Murashige, Ryo; Hayashi, Yuka; Ohmori, Syo; Torii, Ayuko; Aizu, Yoko; Muto, Yasuyuki; Murai, Yuta; Oda, Yuji; Hashimoto, Makoto Tetrahedron, 2011, vol. 67, # 3 p. 641 - 649.
  16. ↑ Walter H Hartung, U.S. Patent 1,995,709 (1935 to Sharp & Dohme Inc)

Further reading

  • GUSTAVO RP (1958). "[Anti-gonadotropic action of possipione]". Quad Clin Ostet Ginecol (in Italian). 13 (7): 307–15. PMID 13579130.
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