2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol Chemical Properties

Boiling point:

544.6±50.0 °C(Predicted)

Density 

1.166±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,2-8°C

solubility 

DMSO: soluble20mg/mL, clear

pka

14.26±0.10(Predicted)

form 

powder

color 

white to beige

InChIKey

LUMKNAVTFCDUIE-VHXPQNKSSA-N

CAS DataBase Reference

128607-22-7

Safety Information

Hazard Codes 

N

Risk Statements 

50/53

Safety Statements 

60-61

RIDADR 

UN 3077 9 / PGIII

WGK Germany 

3

HS Code 

2909.49.1500

Hazardous Substances Data

128607-22-7(Hazardous Substances Data)

2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol Usage And Synthesis

Description

In February 2013, the US FDA approved ospemifene (also referred to as FC1271a), for the treatment ofmoderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA), due tomenopause. It is estimated that there are 150 million postmenopausal women worldwide with 40–70% suffering from VVA. Ospemifene is a selective estrogen receptor (ER) modulator (SERM) and the first nonhormonal, nonestrogen for the treatment of moderate to severe dyspareunia in women with menopausal VVA. It binds to ERα (IC₅₀～800 nM) and ERβ (IC₅₀～1600 nM) with tissue-specific estrogenic agonist/antagonist effects. Treatment with ospemifene increases the thickness of the vaginal tissue thereby decreasing fragility of the tissue and reducing potential for pain during sexual intercourse.

Originator

Tess Diagnostics and Pharmaceuticals/Hormos Medical/QuatRx (Finland)

Uses

Treatment of vaginal atrophy, osteoporosis, and vasomotor symptoms.

Definition

ChEBI: An organochlorine compound that is a selective estrogen receptor modulator; used for treatment of dyspareunia.

brand name

Osphena

Clinical Use

Ospemifene is a SERM that is currently in Phase II/III clinical trials for the treatment of postmenopausal osteoporosis and urogenital atrophy. It is a known metabolite of toremifene, a triphenylethylene derivative used to treat breast cancer.Ospemifene has been shown to have beneficial effects on the bone without significant estrogen-related side effects. The beneficial effect observed on bone stems from this agent's ability to increase osteoblast proliferation and, as a result, to enhance bone mineralization as well as bone formation. Unlike tamoxifen, ospemifene does not induce osteocyte apoptosis.

Synthesis

The drug can be synthesized succinctly in two steps. First, alkylation of commercially available 4-hydroxybenzophenone (130) with ethylene carbonate and catalytic sodium iodide in refluxing toluene provided benzophenone 131 in 94% yield. This was followed by a McMurry coupling involving benzophenone 131 with chloropropiophenone 132 in the presence of zinc powder and titanium tetrachloride in 2-methyltetrahydrofuran. This reaction gave rise to a mixture of triphenylethylenes directly as a 5.5:1 ratio of Z to E isomers which could be separated by crystallization in aqueous methanol to give a mixture of olefins, 98% of which was comprised of the desired Z-isomer corresponding to ospemifene (XVII). The product purity was further improved by recrystallization to give 99.9% of the Z-isomer in 46% yield from 131. Thus, ospemifene was synthesized in two steps and 43% overall yield.

2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol(128607-22-7)Related Product Information

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