566-48-3 Usage
Anti-cancer drugs
Formestane also known as lentaron,is an anti-cancer drug, it is primarily used for the treatment of postmenopausal women with advanced breast cancer, it is also effective in prostate cancer.
Formestane is a androstenedione derivative, and it belongs to an aromatase inhibitor with aminoglutethimide, it is a hormone antineoplastic agent. In physiological conditions, it may competitively inhibit the synthesis of the enzyme leading to estrogen biosynthesis decrease in tissues, then it plays its role in cancer. When the tumor tissue growth relies on the presence of estrogen, in order to inhibit tumor growth, the elimination of tumor estrogen-mediated growth stimulation is necessary. This product is more selective than aminoglutethimide while its activity is 100 to 1000 times of aminoglutethimide, and it does not inhibit the synthesis of adrenal hormones，without having to recharge cortisone, etc . The in vitro inhibition of aromatase enzyme of this product is 60 times stronger than aminoglutethimide.
While it is used alone, the drug can not significantly reduce the pre-menopausal estrogen levels in the blood of women,when it is combined with goserelin (gonadotropin-releasing hormone agonist)， its inhibitory effect of estrogen in premenopausal women is greater than goserelin used alone. Formestane has no cross-resistance with other aromatase inhibitors , it has no side effects of aminoglutethimide. After oral administration，it is rapidly absorbed by gastrointestinal, its peak plasma concentration time is 1 to 1.5 hours, but the peak concentration of individual is of great difference; after intramuscular injection，it can be accumulated at the injection site and be slowly absorbed. It performs Biphasic elimination process, the initial elimination half-life is 2 to 4 days, the terminal elimination half-life is 5 to 10 days. It is mainly metabolized in the liver after oral administration, in the form of glycosides acid metabolites excreted in the urine.
The above information is edited by the lookchem of Tian Ye.
Chemical Properties
Different sources of media describe the Chemical Properties of 566-48-3 differently. You can refer to the following data:
1. Crystallized from aqueous methanol, m.p. 199~202 ℃; crystallized from ethyl acetate, m.p. 203.5~206 ℃. UV absorption maximum (99.5% ethanol): 278nm (ε11030). [α] D20 + 181 ° (C = 7.7, chloroform).
2. Needles
Uses
Different sources of media describe the Uses of 566-48-3 differently. You can refer to the following data:
1. aromatase inhibitors ,it is used for progressive breast cancer.
male hormones, assimilating protein class.
2. An antitumor drug. An aromatase inhibitor.
3. An antitumor drug. An aromatase inhibitor
4. antineoplastic, aromatase inhibitor
production method
Androst-4-ene-3,17-dione (Ⅰ) (1.432g, 5mmo1) is dissolved in 50ml tert-butanol ,add 38mg (0.15mmo1) osmium tetroxide in 2ml t-butanol solution at room temperature, and then 5ml 35% hydrogen peroxide is added, followed by stirring at room temperature for 3 days. After dilution of 100ml brine, and extract with dichloromethane (2 × 100m1). The extract is washed with 100ml brine, , 50ml 10% sodium bisulfite solution, 50ml 10% sodium carbonate solution and 100ml brine, dry over anhydrous sodium sulfate, and concentrate. The residue (1.824g) of the compound (Ⅱ), is dissolved in methanol (10ml),add potassium hydroxide (393mg, 7mmo1) in 3ml methanol . Plus Albert, stirring 10min at 55 ℃. Add 0.3ml of acetic acid and 100ml of brine, and extract with dichloromethane (2 × 100ml). Complex solution, combine, wash with 100ml brine, dry with anhydrous sodium sulfate, and concentrate. The residue (1.727g) by column chromatography on silica gel, wash with hexane-ethyl acetate (7: 3) to give 715mg formestane, yield 47%, mp 200~202 ℃ (acetone).
Description
Different sources of media describe the Description of 566-48-3 differently. You can refer to the following data:
1. 4-hydroxy Androstenedione (4-HAD) is a steroidal inhibitor of aromatase (also known as cytochrome P450 19A1; Ki = 27 nM). As aromatase catalyzes the conversion of androgens to estrogens, aromatase inhibitors, including 4-HAD, are used against hormone-sensitive breast cancer in menopausal women. They are also abused in combination with anabolic steroids in racehorses and athletes. This product is intended for forensic and research applications.
2. Formestane is a potent aromatase inhibitor launched in the UK as a second-line
endocrine treatment for breast cancer. As a synthetic derivative of androstanedione, the
natural substrate for the biosynthesis of estrogen by the enzyme aromatase, formastane
selectively inhibits aromatase and binds to its steroid receptor site to cause a rapid and
sustained fall in circulating estrogen level and, therefore, inhibits tumor growth. In patients
with existing bulky primary tumors, formestane effectively reduces the size of the tumors.
Formastane has apparent tolerability advantages and less side effects than other agents such
as aminoglutethimide.
Originator
Ciba-Geigy (Switzerland)
Definition
ChEBI: A 17-oxo steroid that is androst-4-ene-3,17-dione in which the hydrogen at position 4 is replaced by a hydroxy group. Formestane was the first selective, type I steroidal aromatase inhibitor, suppressing oestrogen production from anabolic steroids or proho
mones. It was formerly used in the treatment of oestrogen-receptor positive breast cancer in post-meopausal women. As it has poor oral bioavailability, it had to be administered by (fortnightly) intramuscular injection. It fell out of use with the subseque
t development of cheaper, orally active aromatase inhibitors. Formestane is listed by the World Anti-Doping Agency as a substance prohibited from use by athletes.
Brand name
Lentaron
Check Digit Verification of cas no
The CAS Registry Mumber 566-48-3 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 5,6 and 6 respectively; the second part has 2 digits, 4 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 566-48:
(5*5)+(4*6)+(3*6)+(2*4)+(1*8)=83
83 % 10 = 3
So 566-48-3 is a valid CAS Registry Number.
InChI:InChI=1/C20H28O2/c1-12-14-5-4-13-15-6-7-18(22)20(15,3)10-8-16(13)19(14,2)11-9-17(12)21/h13,15-16H,4-11H2,1-3H3/t13?,15?,16?,19-,20-/m0/s1
566-48-3Relevant articles and documents
Structure-activity relationships of new A,D-ring modified steroids as aromatase inhibitors: Design, synthesis, and biological activity evaluation
Cepa, Margarida M. D. S.,Tavares Da Silva, Elisiário J.,Correia-Da-Silva, Georgina,Roleira, Fernanda M. F.,Teixeira, Natércia A. A.
, p. 6379 - 6385 (2005)
Inhibition of aromatase is an efficient approach for the prevention and treatment of breast cancer. New A,D-ring modified steroid analogues of formestane and testolactone were designed and synthesized and their biochemical activity was investigated in vitro in an attempt to find new aromatase inhibitors and to gain insight into their structure-activity relationships (SAR). All compounds tested were less active than formestane. However, the 3-deoxy steroidal olefin 3a and its epoxide derivative 4a proved to be strong competitive aromatase inhibitors (Ki = 50 and 38 nM and IC 50 = 225 and 145 nM, respectively). According to our findings, the C-3 carbonyl group is not essential for anti-aromatase activity, but 5α-stereochemistry and some planarity in the steroidal framework is required. Furthermore, modification of the steroidal cyclopentanone D-ring, by construction of a δ-lactone six-membered ring, decreases the inhibitory potency. From the results obtained, it may be concluded that the binding pocket of the active site of aromatase requires planarity in the region of the steroid A,B-rings and the D-ring structure is critical for the binding.
An improved preparation of aromatase inhibitor 4-hydroxyandrost-4-ene-3,17-dione
Ciattini,Morera,Ortar
, p. 1949 - 1952 (1992)
The title compound has been prepared in 47% overall yield from androst-4-ene-3,17-dione (1) by a two-step sequence comprising hydroxylation of 1 with OsO4/H2O2, followed by dehydration of the resultant diols 3 in alkaline medium.
X-ray and deuterium labeling studies on the abnormal ring cleavages of a 5β-epoxide precursor of formestane
Tavares Da Silva, Elisiario J,Roleira, Fernanda M.F,Sa E Melo, M.Luisa,Campos Neves, Andre S,Paixao, Jose A,De Almeida, Maria J,Silva, Manuela R,Andrade, Lourdes C.R
, p. 311 - 319 (2007/10/03)
A new convergent synthesis of the antitumor steroid formestane (4-OHA) 5 has been performed from the easily available epimeric mixture of 5α- and 5β-androst-3-en-17-one 1a and 1b in order to attempt a yield improvement. A two-step oxidative route followed by base-catalyzed isomerization was applied to the 5α- and 5β-epimers 1a and 1b, either as a mixture or separately, leading to the title compound 5. From epimer 1a an efficient process was attained to prepare the desired aromatase inhibitor formestane. Epimer 1b led to the formation of the same compound 5. Additionally, 1b have also been converted in 5β-hydroxyandrostane-3,17-dione 12 and androst-4-ene-3,17-dione 13, revealing an unexpected reactivity of the 3β,4β-epoxy-5β-androstan-17-one intermediate 6 formed from 1b during the first oxidative step with performic acid. Cleavage of the epoxide 6 led to the trans-diaxial and the trans-diequatorial vic-diols 7 and 8 and to the 1,3-diol 9. The formation of the abnormal products 8 and 9 were investigated through X-ray and deuterium labeling studies. Diol 8 was formed through a trans-diequatorial epoxide ring opening and the 1,3-diol 9 was formed through an intramolecular rearrangement involving a 1,2-hydride shift. All the vic-diols 3, 7 and 8 formed, proved to be good precursors for the synthesis of the target compound 5. Copyright
