Plomestane

Last updated
Plomestane
Plomestane.svg
Clinical data
Other namesMDL-18962; Propargylestrenedione; PED; 10-(2-Propyn-1-yl)estr-4-ene-3,17-dione; 10-Propargylestr-4-ene-3,17-dione
ATC code
  • None
Identifiers
  • 10H-(2-Propynyl)-estr-4-ene-3,17-dione
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C21H26O2
Molar mass 310.437 g·mol−1
3D model (JSmol)
  • O=C4\C=C3/[C@@](CC#C)([C@H]2CC[C@@]1(C(=O)CC[C@H]1[C@@H]2CC3)C)CC4
  • InChI=1S/C21H26O2/c1-3-10-21-12-8-15(22)13-14(21)4-5-16-17-6-7-19(23)20(17,2)11-9-18(16)21/h1,13,16-18H,4-12H2,2H3/t16-,17-,18-,20-,21-/m0/s1
  • Key:JKPDEYAOCSQBSZ-OEUJLIAZSA-N

Plomestane (INN Tooltip International Nonproprietary Name, USAN Tooltip United States Adopted Name; former developmental code name MDL-18962; also known as propargylestrenedione, PED) is a steroidal, irreversible aromatase inhibitor which was under development by Marion Merrell Dow/Hoechst Marion Russell (now Hoechst AG) as an antineoplastic agent for the treatment of breast cancer. [1] [2] [3] [4] [5] It was found to be effective in preclinical studies and was also found to produce few adverse effects in human clinical trials, significantly reducing estrogen levels with a single administration. [5] However, development of the drug for clinical use was halted due to "technical issues" and it was never marketed. [6]

Contents

In addition to its activity as an aromatase inhibitor, plomestane has weak androgenic properties. [5]

Synthesis

The chemical synthesis was described: [7] Patent: [8]

Plomestane synthesis.svg

Ketalization of Estr-5(10)-ene-3,17-dione [3962-66-1] (1) with two equivalents of ethylene glycol gives (2). Addition of NBS in water and hence hypobromous acid adds across the olefin to give (3). This rearranges to the oxirane in the presence of sodium methoxide base (4). The Gilman reagent was prepared from 1-(Trimethylsilyl)-1-propyne [6224-91-5] (6) and the reaction gave (7). Removal of the ketal protecting groups in acid, PC11784353 (8) and removal of the trimethyl silyl protecting group in base occurred with concomitant dehydration of the alcohol, completing the synthesis of plomestane (9).

See also

References

  1. ↑ Macdonald F (1997). Dictionary of Pharmacological Agents. CRC Press. p. 1635. ISBN   978-0-412-46630-4 . Retrieved 19 May 2012.
  2. ↑ Morton IK, Hall JM (1999). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer. p. 227. ISBN   978-0-7514-0499-9 . Retrieved 20 May 2012.
  3. ↑ Lombardi P (June 1995). "The irreversible inhibition of aromatase (oestrogen synthetase) by steroidal compounds" . Current Pharmaceutical Design. 1. Bentham Science Publishers: 23–50 (45). doi:10.2174/1381612801666220524190226. S2CID   249298105 . Retrieved 20 May 2012.
  4. ↑ Kreider RB, Leutholtz BC, Katch FI, Katch VL (2009). Exercise and Sport Nutrition. Exercise & Sport Nutrition. p. 350. ISBN   978-0-9742965-6-2 . Retrieved 20 May 2012.
  5. 1 2 3 Kelloff GJ, Lubet RA, Lieberman R, et al. (January 1998). "Aromatase inhibitors as potential cancer chemopreventives". Cancer Epidemiology, Biomarkers & Prevention. 7 (1): 65–78. PMID   9456245.
  6. ↑ Avendaño C, Menéndez JC (4 June 2008). Medicinal Chemistry of Anticancer Drugs. Elsevier. p. 69. ISBN   978-0-444-52824-7 . Retrieved 20 May 2012.
  7. ↑ Bednarski, P. J., Nelson, S. D. (January 1989). "Interactions of thiol-containing androgens with human placental aromatase". Journal of Medicinal Chemistry. 32 (1): 203–213. doi:10.1021/jm00121a037.
  8. ↑ Cynthia L. Rand, U.S. patent 5,516,922 (1996 to Aventis Pharmaceuticals Inc).



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