Fulvestrant

Base Information

• Chemical Name: Fulvestrant
• CAS No.: 129453-61-8
• Molecular Formula: C32H47F5O3S
• Molecular Weight: 606.781
• Hs Code.: 2937230000
• European Community (EC) Number: 642-998-6
• NSC Number: 719276
• UNII: 22X328QOC4
• DSSTox Substance ID: DTXSID4022369
• Nikkaji Number: J401.163E
• Wikipedia: Fulvestrant
• Wikidata: Q5508491
• NCI Thesaurus Code: C1379
• RXCUI: 282357
• Pharos Ligand ID: D7416FK94ZF1
• Metabolomics Workbench ID: 145676
• ChEMBL ID: CHEMBL1358
• Mol file: 129453-61-8.mol

Synonyms:7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)estra-1,3,5(10)-triene-3,17-diol;Faslodex;fulvestrant;ICI 182,780;ICI 182780;ICI-182780;ICI182780;ZM 182780;ZM-182780;ZM182780

Chemical Property of Fulvestrant

Chemical Property:

• Appearance/Colour: white powder
• Vapor Pressure: 3.95E-19mmHg at 25°C
• Melting Point: 104-106°C
• Refractive Index: 1.521
• Boiling Point: 674.8 °C at 760 mmHg
• PKA: 10.27±0.70(Predicted)
• Flash Point: 361.9 °C
• PSA: 76.74000
• Density: 1.201 g/cm³
• LogP: 9.54830
• Storage Temp.: 2-8°C
• Solubility.: DMSO: >5mg/mL
• XLogP3: 9.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 9
• Rotatable Bond Count: 14
• Exact Mass: 606.31660734
• Heavy Atom Count: 41
• Complexity: 854

Purity/Quality:

99%min ^*data from raw suppliers

Fulvestrant ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: CC12CCC3C(C1CCC2O)C(CC4=C3C=CC(=C4)O)CCCCCCCCCS(=O)CCCC(C(F)(F)F)(F)F
• Isomeric SMILES: C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)[C@@H](CC4=C3C=CC(=C4)O)CCCCCCCCCS(=O)CCCC(C(F)(F)F)(F)F
• Recent ClinicalTrials: Study Assessing the Efficacy and Safety of Alpelisib Plus Fulvestrant or Letrozole, Based on Prior Endocrine Therapy, in Patients With PIK3CA Mutant, HR+, HER2- Advanced Breast Cancer Who Have Progressed on or After Prior Treatments
• Recent EU Clinical Trials: PHASE 1B/2, OPEN-LABEL, MULTICENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, PHARMACODYNAMICS, AND ANTITUMOR ACTIVITY OF PF-07220060 IN COMBINATION WITH PF-07104091 PLUS ENDOCRINE THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS
• Recent NIPH Clinical Trials: Basket study of tucatinib and trastuzumab in solid tumors with HER2 alterations
• Description: Fulvestrant was launched in the US as a novel once monthly injectable steroidal estrogen antagonist for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women with disease progression following estrogen therapy. This 7a-alkylsulphinyl derivative of estradiol can be prepared in 10 steps from 6,7- didehydro-19-nor-testosterone by successive conjugate addition of the organocuprate derived from O-protected 9-bromononan-l-o1 followed by aromatization of the resulting enone, then activation of the protected primary alcohol, substitution with 4,4,5,5,5- pentafluoropentanthiol and oxidation to the sulfoxide. Fulvestrant is the first “pure” estrogen antagonist from a novel class known as selective estrogen receptor down regulators (SERDs). It binds to the estrogen receptor (ER), with affinity close to that of estradiol and 100 fold greater than that of tamoxifen (a partial estrogen antagonist), preventing estrogen-stimulated gene activation, thereby interfering with the estrogenrelated processes essential for cell-cycle completion. Fulvestrant also appears to downregulate the ER by 80-90% often to non detectable level both in vitro and in vivo. In comparison to tamoxifen, fulvestrant is devoid of systemic estrogenic activity, it displays no uterotrophic activity and is able to block the uterine stimulation of estradiol or tamoxifen. Furthermore, fulvestrant completely blocks the cell growth in tamoxifen-resistant breast cancer cell-lines and prevents growth of tamoxifen resistant tumor in mice. In clinical trials, it was also shown that fulvestrant is comparable to anastrozole (a third generation aromatase inhibitor) both in efficacy and tolerability in postmenopausal women with tamoxifen-resistant advanced breast cancers.
• Uses: A novel steroidal estrogen antagonist reported to lack any partial agonist activity. Antineoplastic (hormonal). antiestrogen
• Clinical Use: Treatment of postmenopausal women with oestrogenreceptor- positive, locally advanced or metastatic breast cancer
• Drug interactions: Potentially hazardous interactions with other drugs None known

Technology Process of Fulvestrant

There total 57 articles about Fulvestrant which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 95.0%

(+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol (153004-31-0) → fulvestrant (129453-61-8,1316849-17-8,1807900-80-6,407577-53-1)

Guidance literature:

With dihydrogen peroxide; acetic acid; In water; ethyl acetate; at 40 ℃; for 4h; Inert atmosphere; Schlenk technique;

DOI:10.1039/c5cc05805h

Reference yield: 82.0%

7β-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5-trien-3,17β-diol → fulvestrant (129453-61-8,1316849-17-8,1807900-80-6,407577-53-1)

Guidance literature:

With dihydrogen peroxide; acetic acid; In ethyl acetate;

Reference yield: 32.0%

(7R,13S)-3-methoxy-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol (1221256-46-7) → fulvestrant (129453-61-8,1316849-17-8,1807900-80-6,407577-53-1)

Guidance literature:

With aluminum (III) chloride; thiourea; In dichloromethane; at 20 - 55 ℃; Product distribution / selectivity;

upstream raw materials:

(+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol

fulvestrant 17β-acetate

(7R,13S)-3-methoxy-13-methyl-7-(9-(4,4,5,5,5-pentafluoropentylsulfinyl)nonyl)-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-ol

4,4,5,5,5-pentafluorpentan-1-ol

Downstream raw materials:

ICI 182,780-17-ketone

(+)-(7α)-[9-(4,4,5,5,5-pentafluoropentylsulfanyl)nonyl]estra-1,3,5(10)-triene-3,17β-diol

Refernces

• 1、 Caprioglio, Diego,Fletcher, Stephen P.. "An alternative synthesis of the breast cancer drug fulvestrant (Faslodex): catalyst control over C-C bond formation". . p. 14866 - 14868. Retrieved 2015.
• 2、 -. "Method for preparing fulvestrant and intermediates". Paragraph 0055-0058. . Retrieved 2020/04/17.