128607-22-7 Usage
Description
2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol, also known as ospemifene or FC1271a, is an organochlorine compound that functions as a selective estrogen receptor modulator (SERM). It is the first nonhormonal, nonestrogen treatment for moderate to severe dyspareunia in women with menopausal vulvar and vaginal atrophy (VVA). Ospemifene exhibits tissue-specific estrogenic agonist/antagonist effects by binding to estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) with respective IC50 values of approximately 800 nM and 1600 nM. 2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol was approved by the US FDA in February 2013 and is marketed under the brand name Osphena.
Uses
Used in Pharmaceutical Industry:
2-(4-(4-chloro-1,2-diphenyl-but-1-enyl)phenoxy)ethanol is used as a therapeutic agent for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) caused by menopause. It addresses the needs of an estimated 150 million postmenopausal women worldwide, with 40–70% suffering from VVA. The treatment with ospemifene increases the thickness of vaginal tissue, reducing its fragility and the potential for pain during sexual intercourse.
Additionally, ospemifene has been studied for its potential use in treating osteoporosis and vasomotor symptoms, further expanding its applications in the pharmaceutical industry for addressing postmenopausal health concerns.
Originator
Tess Diagnostics and
Pharmaceuticals/Hormos
Medical/QuatRx (Finland)
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.
Check Digit Verification of cas no
The CAS Registry Mumber 128607-22-7 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,8,6,0 and 7 respectively; the second part has 2 digits, 2 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 128607-22:
(8*1)+(7*2)+(6*8)+(5*6)+(4*0)+(3*7)+(2*2)+(1*2)=127
127 % 10 = 7
So 128607-22-7 is a valid CAS Registry Number.
InChI:InChI=1/C24H23ClO2/c25-16-15-23(19-7-3-1-4-8-19)24(20-9-5-2-6-10-20)21-11-13-22(14-12-21)27-18-17-26/h1-14,26H,15-18H2/b24-23-
128607-22-7Relevant articles and documents
Design, synthesis, anti-proliferative evaluation and docking studies of 1: H -1,2,3-triazole tethered ospemifene-isatin conjugates as selective estrogen receptor modulators
Kumar, Sumit,Gu, Liang,Palma, Gabriella,Kaur, Mandeep,Singh-Pillay, Ashona,Singh, Parvesh,Kumar, Vipan
, p. 3703 - 3713 (2018)
A library of 1H-1,2,3-triazole-tethered ospemifene-isatin and ospemifene-spiroisatin conjugates have been synthesized and evaluated for their anti-proliferative activities against MCF-7 and MDA-MB-231 cell lines. The evaluation studies revealed that compound 11j was the most potent with an IC50 value of 1.56 μM against the MCF-7 cell line. Compounds 11k and 11l also displayed a similar trend, with several-fold lower effective concentrations in ER+ cells than in ER- cells. SAR studies revealed that conjugates having a bromo-substituent at the C-5 and C-7 positions of the isatin ring with ethyl/propyl as the spacer were observed to be active with the most potent compound being ～30 times more potent than Tamoxifen against the MCF-7 cell line. The evaluation results were further supported by docking studies and the stronger binding affinity of the synthesized conjugates was attributed to their greater structural bulk and greater occupation of the ERα active site.
METHOD FOR PRODUCING TRIPHENYLBUTENE DERIVATIVE
-
, (2017/11/07)
We provide a novel and useful process for preparing triphenyl-butene derivative. A process for the preparation of a compound represented by Formula (IV): wherein R1 is hydrogen or substituted or unsubstituted alkyl, characterized by reacting a compound represented by Formula (V): with a compound represented by Formula (VI): wherein R1 has the same meaning as defined above, in the presence of 1) a polyvalent metal chloride, 2) a reducing agent and 3) an alkali metal salt and/or a substituted or unsubstituted phenol.
PROCESS FOR PREPARATION OF OSPEMIFENE
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Paragraph 0134, (2016/08/17)
The present invention relates to a process for the preparation of ospemifene and pharmaceutically acceptable salts thereof which comprises the step of recycling the undesired E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol to generate an isomeric mixture of Z,E-4-(4-hydroxy-1,2-diphenylbut-1-enyl)phenol.
