174592-47-3

Basic information

• Product Name: (E)-4-Hydroxytamoxifen
• Synonyms: (E)-4-Hydroxytamoxifen;cis-4-Hydroxy Tamoxifen Discontinued;4-[(1E)-1-[4-[2-(DiMethylaMino)ethoxy]phenyl]-2-phenyl-1-buten-1-yl]phenol
• CAS NO: 174592-47-3
• Molecular Formula: C₂₆H₂₉NO₂
• Molecular Weight: 387.52
• Product Categories: Aromatics;Drug Analogues;Intermediates & Fine Chemicals;Metabolites & Impurities;Pharmaceuticals;Aromatics, Drug Analogues, Metabolites & Impurities, Pharmaceuticals, Intermediates & Fine Chemicals
• Mol File: 174592-47-3.mol

Chemical Properties

• Boiling Point: 514.4°C at 760 mmHg
• Flash Point: 264.9°C
• Appearance: /
• Density: 1.092g/cm³
• Vapor Pressure: 3.35E-11mmHg at 25°C
• Refractive Index: 1.596
• Storage Temp.: Amber Vial, -20°C Freezer, Under Inert Atmosphere
• Solubility: Chloroform
• CAS DataBase Reference: (E)-4-Hydroxytamoxifen(CAS DataBase Reference)
• NIST Chemistry Reference: (E)-4-Hydroxytamoxifen(174592-47-3)
• EPA Substance Registry System: (E)-4-Hydroxytamoxifen(174592-47-3)

Safety Data

• Hazardous Substances Data: 174592-47-3(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
(E)-4-Hydroxytamoxifen is used as an active pharmaceutical ingredient for the development of medications targeting hormone-dependent cancers, such as breast cancer. Its anti-estrogenic properties help in blocking the effects of estrogen, a hormone that can promote the growth of certain cancer cells.
Used in Cancer Treatment:
(E)-4-Hydroxytamoxifen is used as a therapeutic agent for the treatment of hormone-dependent cancers, particularly breast cancer. It works by competing with estrogen for binding to its receptors, thereby inhibiting the growth and proliferation of cancer cells that rely on estrogen for survival and growth.
Used in Research Applications:
(E)-4-Hydroxytamoxifen is used as a research tool in the study of estrogen receptor signaling pathways and the development of novel anti-estrogenic drugs. Its structural and functional similarities to Tamoxifen make it a valuable compound for investigating the mechanisms of estrogen-dependent cancers and identifying potential therapeutic targets.

InChI:InChI=1/C26H29NO2/c1-4-25(20-8-6-5-7-9-20)26(21-10-14-23(28)15-11-21)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

• 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 
• 124-40-3 dimethyl amine 
• 147323-02-2 E/Z-1-[4-(2-bromoethoxy)phenyl]-1-(4-hydroxyphenyl)-2-phenylbutene 
• 68047-06-3 Z-1-<4-(2-dimethylaminoethoxy)phenyl>-1-(4-hydroxyphenyl)-2-phenyl-1-butene 
• 106-41-2 4-bromo-phenol 
• 36603-49-3 4-(tetrahydropyran-2'-yloxy)-1-bromobenzene 
• 622-86-6 2-chloroethoxybenzene 
• 108-95-2 phenol 
• 119757-57-2 (E,Z)-1-<4-(2-chloroethoxy)phenyl>-1-(4-hydroxyphenyl)-2-phenyl-1-butene 
• 103628-22-4 1--2-phenyl-butan-1-one 
• 94972-95-9 4-hydroxy-4'-benzyloxybenzophenone 

Relevant articles and documents

Simple and Efficient Production of (Z)-4-Hydroxytamoxifen, a Potent Estrogen Receptor Modulator

A McMurry coupling reaction and selective crystallization were used to develop a simple and efficient two-step synthesis of (Z)-4-hydroxytamoxifen (2a). This compound is an active metabolite of tamoxifen, a selective estrogen receptor (ER) modulator widely used to treat breast cancer. The synthesis employed 1,1-bis(4-hydroxyphenyl)-2-phenylbut-1-ene (1) as a useful building block.

New approach based on immunochemical techniques for monitoring of selective estrogen receptor modulators (SERMs) in human urine

Antiestrogenic compounds such as tamoxifen, toremifen and chlomifen are used illegally by athletes to minimize physical impacts such as gynecomastia resulting from the secondary effects of anabolic androgenic steroids, used to increase athletic efficiency unlawfully. The use of these compounds is banned by the World Anti-Doping Agency (WADA) and controls are made through analytical methodologies such as HPLC–MS/MS, which do not fulfil the sample throughput requirements. Moreover, compounds such as tamoxifen are also used to treat hormone receptor-positive breast cancer (ER +).Therapeutic drug monitoring (TDM) of tamoxifen may also be clinically useful for guiding treatment decisions. An accurate determination of these drugs requires a solid phase extraction of patient serum followed by HPLC–MS/MS. In the context of an unmet need of high-throughput screening (HTS) and quantitative methods for antiestrogenic substances we have approached the development of antibodies and an immunochemical assay for the determination of these antiestrogenic compounds. The strategy applied has taken into consideration that these drugs are metabolized and excreted in urine as the corresponding 4-hydroxylated compounds. A microplate-based ELISA procedure has been developed for the analysis of these metabolites in urine with a LOD of 0.15, 0.16 and 0.63 μg/L for 4OH-tamoxifen, 4OH-toremifen and 4OH-clomifen, respectively, much lower than the MRPL established by WADA (20 μg/L).

TARGETED DRUG-FORMALDEHYDE CONJUGATES AND METHODS OF MAKING AND USING THE SAME

The invention provides a prodrug platform technology for improving the therapeutic value of a variety of parent drug compounds by altering and improving drug characteristics such as aqueous solubility, hydrolytic stability, therapeutic index, toxicity profile, pharmacokinetics and selectivity while allowing the potential for synthetic elaboration. The prodrug platform is particularly well suited for targeting therapeutic drugs, including anti-tumor drugs and antibiotics, to specific receptors on target cells (e.g., cancer cells and bacteria). The platform is a technology for providing an improved, preactivated form of a therapeutic drug, and for optionally targeting such drug to target cells or biological molecules. The invention is broadly applicable to many different therapeutic drugs, as well as to a variety of diseases and conditions, including a variety of forms of cancer and bacterial infections.

Chemically stable compositions of 4-hydroxy tamoxifen

A class of chemically stable 4-hydroxy tamoxifen compositions is characterized by roughly equal amounts of the Z-4-hydroxy tamoxifen and E-4-hydroxy tamoxifen isomers, such that the potency of the compositions is not affected adversely by the isomerizatio

Synthesis and Sulfatase Inhibitory Activities of (E)- and (Z)-4-Hydroxytamoxifen Sulfamates

We report the development of (E)- and (Z)-4-hydroxytamoxifen sulfamates as estrone sulfatase inhibitors, potential therapeutic agents for the treatment of breast cancer. Both compounds competitively inhibit estrone sulfatase isolated from rat liver with apparent Ki of 35.9 μM for (E)-4-hydroxytamoxifen sulfamate and an apparent Ki of >500 μM for the (Z) isomer.

The Use of the Perfluorotolyl Protecting Group in the Synthesis of Pure Z and E Isomers of 4-Hydroxytamoxifen -1-(4-hydroxyphenyl)-2-phenyl-1-butene>

The perfluorotolyl protecting group has been used in the synthesis of pure Z and E isomers of 4-hydroxytamoxifen (4a), a potent metabolite of the anticancer drug, tamoxifen (1a). 4-(Perfluorotolyloxy)phenyl magnesium bromide underwent addition to the carbonyl group of the easily prepared versatile ketone, 1--2-phenyl-1-butanone (7), without affecting the chloroethoxy group.Acid catalysed dehydration of the resulting carbinol gave a 1:1 mixture of isomeric ethers, (6a) and (6b), that were easily separated by chromatography and respectively converted to the Z (4a) and E (4b) isomers of 4-hydroxytamoxifen.The property of the perfluorotolyl function in enabling the separation of geometrical isomers is attributed to a combination of its lipophilicity and electron withdrawal.

Hydroxy derivatives of tamoxifen

In the exploration of the structural features that affect the RBA (binding affinity for the estrogen receptor of rat uterus relative to that of estradiol) in the tamoxifen [trans-(Z)-1-[4-(dimethylamino)ethoxy]-1,2-diphenyl-1-butene] series, several derivatives variously substituted in the 1-phenyl group have been synthesized. In the tamoxifen series, the descriptors E and Z, which define the configuration of the geometrical isomers and depend on the location and nature of substituents in the aromatic moieties and the ethyl group, may vary, although the relative configuration (cis or trans) does not. In order to avoid confusion the terms cis and trans will be used in this paper to refer to the relative positions of the 4-[2-(dimethylamino)ethoxy]phenyl and ethyl (or hydroxyethyl, hydroxypropyl, or bromo) substituents attached to the ethene moiety]. The final stage of each synthesis involved acid-catalyzed dehydration of a tertiary alcohol, and, in contrast to the known 3- and 4-hydroxy derivatives which were obtained as near-equimolar cis,trans mixtures, only the trans forms of the 2-hydroxy, 2-methyl, 2,4-dihydroxy, and 4-hydroxy-2-methyl derivatives were obtained. Also, in contrast to the trans forms of the 3- and 4-hydroxy derivatives, which are readily equilibrated to cis,trans mixtures, the trans 2-hydroxy derivative could not be isomerized. Tamoxifen and 2-methyltamoxifen had similar RBA's (~1% of that of E2), but that of 2-hydroxytamoxifen was much lower (0.1%). Introduction of a second hydroxyl group (2,4-dihydroxy derivative) enhanced the RBA, and for the 4-hydroxy-2-methyl derivative, the RBA and growth inhibitory activity against the MCF-7 mammary tumor cell line in vitro were high and comparable to those of 4-hydroxytamoxifen, a metabolite of the parent drug. Tamoxifen derivatives hydroxylated at positions 3 or 4 of the 1-butene moiety and the 5-hydroxy-1-pentene analogue were also synthesized, but they had very low RBA values.