68047-06-3

Basic information

• Product Name: 4-HYDROXYTAMOXIFEN
• Synonyms: trans-4-Hydroxytamoxifen, (Z)-4-(1-[4-(Dimethylaminoethoxy)phenyl]-2-phenyl-1-butenyl)phenol;(Z)-3,4-Diphenyl-4-[4-[2-(dimethylamino)ethoxy]phenyl]-3-buten-1-ol;2-[4-[(E)-1-(4-Hydroxyphenyl)-2-phenyl-1-butenyl]phenoxy]-N,N-dimethylethanamine;4-[(E)-1-[4-[2-(Dimethylamino)ethoxy]phenyl]-2-phenyl-1-butenyl]phenol;cis-4-Hydroxytamoxifen;N,N-Dimethyl-2-[4-[(E)-1-(4-hydroxyphenyl)-2-phenyl-1-butenyl]phenoxy]ethanamine;4-(1-(4-(dimethylaminoethoxy)phenyl)-2-phenyl-1-butenyl)phenol;(Z)-4-(1-[4-(Dimethylaminoethoxy)phenyl]-2-phenyl-1-butenyl)phenol
• CAS NO: 68047-06-3
• Molecular Formula: C₂₆H₂₉NO₂
• Molecular Weight: 387.51
• Product Categories: Drug Analogues;Intermediates & Fine Chemicals;Pharmaceuticals;Steroids;Aromatics;Metabolites & Impurities
• Mol File: 68047-06-3.mol
• Article Data: 16

Chemical Properties

• Melting Point: 105-107°C
• Boiling Point: 513.45°C (rough estimate)
• Flash Point: 264.9°C
• Appearance: white/powder
• Density: 1.1005 (rough estimate)
• Vapor Pressure: 3.35E-11mmHg at 25°C
• Refractive Index: 1.6000 (estimate)
• Storage Temp.: 2-8°C
• Solubility: 95% ethanol: 20 mg/mL
• PKA: 10.35±0.15(Predicted)
• Stability: Stable. Store cool. Incompatible with strong oxidizing agents.
• CAS DataBase Reference: 4-HYDROXYTAMOXIFEN(CAS DataBase Reference)
• NIST Chemistry Reference: 4-HYDROXYTAMOXIFEN(68047-06-3)
• EPA Substance Registry System: 4-HYDROXYTAMOXIFEN(68047-06-3)

Safety Data

• Hazard Codes: Xn
• Statements: 20/21/22-63
• Safety Statements: 22-23-36
• WGK Germany: 3
• RTECS: SL1210000
• Hazardous Substances Data: 68047-06-3(Hazardous Substances Data)

Usage

Chemical Properties

Powder

Uses

Different sources of media describe the Uses of 68047-06-3 differently. You can refer to the following data:
1. A hydroxylated analogue of tamoxifen with anti-estrogenic properties. A metabolite of Tamoxifen.
2. A metabolite of Tamoxifen (T006000). A hydroxylated analogue of Tamoxifen with anti-estrogenic properties.
3. tamoxifen metabolite, anti-estrogen, see Tamoxifen 1,01038

General Description

A cell-permeable, active metabolite of Tamoxifen (Cat. No. 579000) that acts as a potent inhibitor of PKC. It is more potent than the parent compound and inhibits PKC by modifying its catalytic domain. Also available as a 10 mM solution in EtOH (Cat. No. 508225).

Biological Activity

estrogen receptors (er) are members of the superfamily of ligand-modulated nuclear receptors that mediate the actions of steroid hormones, vitamin d, retinoids, and thyroid hormones. er is activated in vivo when bound by naturally occurring estrogens such as 17α-estradiol. in addition to regulating these physiological processes, estrogen also plays a central role in stimulating breast cancer growth. (z)-tamoxifen is a first generation selective er modulators that is currently approved by the fda and is widely used to treat estrogen-dependent breast cancers. its active metabolite, (z)-4-hydroxytamoxifen, is a potent estrogen receptor modulator.

Biochem/physiol Actions

Cell permeable: yes

in vitro

(z)-4-hydroxytamoxifen binds to er with 8-fold higher affinity than tamoxifen. it was found that only the z isomer has the required antiestrogenic activity; the (e)-4-hydroxytamoxifen has only about 5% of its affinity for the er [1].

in vivo

the antioestrogenic activities of (z)-4-hydroxytamoxifen and tamoxifen were determined after oral administration. (z)-4-hydroxytamoxifen was administered to groups of immature rats which also received s.c. injections of 0-2 μg oestradiol. both compounds produced a dose-related decrease in uterine wet weight when compared with the oestradiol-treated controls. at a dose of 1 μg/day, the antiuterotrophic effects of (z)-4-hydroxytamoxifen and tamoxifen were not significantly different but at 5μg/day, (z)-4-hydroxytamoxifen was more active (p < 0.01). (z)-4-hydroxytamoxifen therefore appears to retain its potent antioestrogenic activity after oral administration [2].

references

[1] donna d. yu and barry m. forman. simple and efficient production of (z)-4-hydroxytamoxifen, a potent estrogen receptor modulator. j. org. chem. 2003, 68, 9489-9491[2] jordan vc, collins mm, rowsby l, prestwich g. a monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. j endocrinol. 1977 nov;75(2):305-16.

InChI:InChI=1/C26H29NO2/c1-4-25(20-10-14-23(28)15-11-20)26(21-8-6-5-7-9-21)22-12-16-24(17-13-22)29-19-18-27(2)3/h5-17,28H,4,18-19H2,1-3H3/b26-25-

Upstream product

• 124-40-3 dimethyl amine 
• 147323-02-2 E/Z-1-[4-(2-bromoethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenylbutene 
• 611-99-4 4,4'-Dihydroxybenzophenone 
• 93-55-0 1-phenyl-propan-1-one 
• 91221-46-4 1,1-bis(4-hydroxyphenyl)-2-phenyl-1-butene 
• 107-99-3 2-(dimethylamino)ethyl chloride 
• 10540-29-1 tamoxifen 
• 75-03-6 ethyl iodide 
• 93790-54-6 [2-(4-iodophenoxy)ethyl]dimethylamine 
• 2633-75-2 ethylzinc chloride 
• 106-41-2 4-bromo-phenol 
• 36603-49-3 4-(tetrahydropyran-2'-yloxy)-1-bromobenzene 
• 126402-32-2 1-(trimethylsilyl)-1-(4-<(2-tetrahydropyranyl)oxy>phenyl)-2-phenyl-1-butene 
• 96212-84-9 (E)-1-bromo-2-phenyl-1-(trimethylsilyl)-1-butene 

Downstream Products

• 76117-70-9 (E)-4-{1-[4-(2-dimethylaminoethoxy)phenyl]-2-phenylbut-1-enyl}phenyl acetate 
• 1454890-27-7 4-((E)-1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-en-1-yl)phenyl 4-(-2-((4-methoxy-1H,1'H-[2,2'-bipyrrol]-5-yl)methylene)-3,5-dimethyl-2H-pyrrol-4-yl)-4-oxobutanoate 
• 1454890-28-8 4-((E)-1-(4-(2-(dimethylamino)ethoxy)phenyl)-2-phenylbut-1-enyl)phenyl 10-((Z)-2-((4-methoxy-1H,1'H-2,2'-bipyrrol-5-yl)methylene)-3,5-dimethyl-2H-pyrrol-4-yl)-10-oxodecanoate 
• 174592-47-3 trans 4-hydroxytamoxifen 
• 199541-66-7 4-hydroxytamoxifen quinone methide 

Relevant articles and documents

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method development for screening of potential tamoxifen-drug/herb interaction via in vitro cytochrome P450 inhibition assay

Screening for potential drug-drug interaction (DDI) or herb-drug interaction (HDI) using in vitro cytochrome P450 inhibition (IVCI) assays requires robust analytical methods with high sensitivity and reproducibility. Utilization of liquid chromatography-mass spectrometry (LC-MS) for analyte quantification is often hampered by the presence of non-volatile IVCI sample buffer constituents that often results in ion suppression. In this study, to enable screening of drug interactions involving tamoxifen (TAM) metabolism using IVCI-LC-MS/MS, a liquid–liquid extraction (LLE) method was developed and optimized for sample clean-up. Utilization of chloroform as extraction solvent and adjustment of sample pH to 11 was found to result in satisfactory recovery (>70%) and low ion suppression (A LC-MS/MS method was subsequently developed and validated for simultaneous quantification of major TAM metabolites, such as N-desmethyltamoxifen (NDT), endoxifen (EDF) and 4-hydroxytamoxifen (HTF) to enable IVCI sample analysis. Satisfactory separation of E-/Z-isomers of endoxifen with peak resolution (Rs) of 1.9 was achieved. Accuracy and precision of the method was verified within the linear range of 0–50 ng/mL for NDT, 0–25 ng/mL for HTF and 0–25 ng/mL for EDF (E/Z isomers). Inhibitory potency (IC50, Ki and mode of inhibition) of known CYP inhibitors and Strobilanthes crispus extract was then evaluated using the validated method. In summary, the results demonstrated applicability of the developed LLE and validated LC-MS/MS method for in vitro screening of DDI and HDI involving TAM metabolism.

Photochemical Activation of Tertiary Amines for Applications in Studying Cell Physiology

Representative tertiary amines were linked to the 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group (PPG) to create photoactivatable forms suitable for use in studying cell physiology. The photoactivation of tamoxifen and 4-hydroxytamoxifen, which can be used to activate Cre recombinase and CRISPR-Cas9 gene editing, demonstrated that highly efficient release of bioactive molecules could be achieved through one- and two-photon excitation (1PE and 2PE). CyHQ-protected anilines underwent a photoaza-Claisen rearrangement instead of releasing amines. Time-resolved spectroscopic studies revealed that photorelease of the tertiary amines was extremely fast, occurring from a singlet excited state of CyHQ on the 70 ps time scale.

Biomimetic oxidation of aromatic xenobiotics: Synthesis of the phenolic metabolites from the anti-HIV drug efavirenz

We report the oxidation of the first line anti-HIV drug efavirenz (EFV), mediated by a bio-inspired nonheme Fe-complex. Depending upon the experimental conditions this system can be tuned either to yield the major EFV metabolite, 8-hydroxy-EFV, in enantiomerically pure form or to mimic cytochrome P450 (CYP) activity, yielding 8-hydroxy-EFV and 7-hydroxy-EFV, the two phenolic EFV metabolites reported to be formed in vivo. The successful oxidation of the anti-estrogen tamoxifen and the equine estrogen equilin into their CYP-mediated metabolites supports the general application of bio-inspired nonheme Fe-complexes in mirroring CYP activity.