ジエチルスチルベストロール 化學(xué)特性,用途語,生産方法
外観
白色?わずかにうすい褐色, 結(jié)晶性粉末?粉末
溶解性
エタノール及びアセトンに溶け、水にほとんど溶けない。
解説
ジエチルスチルベストロール，合成エストロゲン(卵胞ホルモンあるいは発情ホルモン)．ステロイド骨格を有しないが，17β-エストラジオールのB，C環(huán)を開いた構(gòu)造に類似している．板狀晶．融點(diǎn)171～173 ℃(エタノールまたはベンゼン)．合成エストロゲンで活性型はトランス型．胎児に対する催奇形性がある．かつては，切迫流産防止剤や経口避妊薬として用いられたが，副作用のため現(xiàn)在では使用禁止となっている．強(qiáng)い魚毒活性を示す．冠動脈血管拡張剤，抗悪性腫瘍薬．LD50 34 mg/kg(ラット，腹腔內(nèi))．
用途
合成非ステロイド性エストロゲン(女性ホルモン)として流産又は早産防止薬、避妊薬、前立腺がん治療薬、乳がん治療薬、家畜の成長促進(jìn)薬であった。
効能
子宮収縮抑制薬, エストロゲン受容體作動薬
化學(xué)的特性
Diethylstilbestrol is an odorless, white crystalline powder, with a molecular weight of 268.36. Its cisisomer tends to revert to the trans-form. It is a nonsteroidal, synthetic stilbene derivative with estrogenic activity. recomended solvents are DMSO, DMF and ethanol, even in these solvents do not store in solution for any prolonged period of time.
使用
Diethylstilbestrol is a synthetic nonsteroidal estrogen that was
formerly used in estrogenic hormone therapy (for menstrual
disorders, postpartum breast engorgement, postcoital contraceptive,
prevention of spontaneous abortion) and in chemotherapy
of various cancers, including postmenopausal breast
cancer and prostate cancer. It was also used in biomedical
research and veterinary medicine (growth promoter for cattle
and sheep; veterinary drug to treat estrogen deficiency disorders).
定義
ChEBI: Diethylstilbestrol is an olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups. It has a role as an antineoplastic agent, a carcinogenic agent, a xenoestrogen, an EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor, an antifungal agent, an endocrine disruptor, an EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor, an autophagy inducer and a calcium channel blocker. It is a polyphenol and an olefinic compound.
適応癥
Diethylstilbestrol is one of the older synthetic estrogens in use. It was used to treat prostate cancer but is now rarely used for this purpose because of its adverse effects，although it is occasionally used in postmenopausal women with breast cancer. It is taken orally in tablet form.
世界保健機(jī)関（WHO）
Diethylstilbestrol, a synthetic estrogen which is a stilbene
derivative, was introduced into obstetric practice in the late 1940s and
subsequently widely used for the treatment of threatened abortion. This use was
later shown to be associated with an increased risk of vaginal cancer in the
offspring which resulted in restrictive regulatory action in several countries.
Diethylstilbestrol and other stilbenes remain available in many countries, however,
for the treatment of certain hormone-dependent neoplasms including carcinoma of
the prostate and postmenopausal breast cancer.
(Reference: (WHODI) WHO Drug Information, 77.1, 16, 1977)
空気と水の反応
Insoluble in water.
反応プロフィール
Diethylstilbestrol is incompatible with strong oxidizing agents, strong bases, acid chlorides and acid anhydrides .
火災(zāi)危険
Flash point data for Diethylstilbestrol are not available; however, Diethylstilbestrol is probably combustible.
副作用
These include sodium retention and oedema，nausea，gynaecomastia and impotence in men, and venous and arterial thrombosis. It can cause bone pain and hypercalcaemia when used for breast cancer.
安全性プロファイル
Confirmed carcinogen
producing skin, liver, and lung tumors in
exposed humans as well as uterine and other
reproductive system tumors in the female
offspring of exposed women. Experimental
carcinogenic, neoplas tigenic, tumorigenic,
and teratogenic data. A transplacental
carcinogen. A human teratogen by many
routes. Poison by intraperitoneal and
subcutaneous routes. It causes glandular
system effects by sktn contact. Human
reproductive effects by ingestion: abnormalspermatogenesis; changes in testes, epididymis, and sperm duct; menstrual cycle
changes or disorders; changes in female
ferulity; unspecified maternal effects;
developmental abnormalities of the fetal
urogenital system; germ cell effects in
offspring; and delayed effects in newborn.
Implicated in male impotence and
enlargement of male breasts. Other
experimental reproductive effects.
Mutation data reported. When heated to
decomposition it emits acrid smoke and
fumes. See also ETHINYL ESTRADIOL.
合成
In 1993, using phenol (DIET-001) as a raw material, Diethylstilbestrol was synthesized through five steps. Treatment of phenol (DIET-001) with propionic acid at 90 °C provides ketone DIET-002, followed by methylation of DIET-002 with dimethyl sulfate to afford ether DIET-003. Next, DIET-003 and Hg–Al are heated in MeOH, and then treated with conc. HCl to give DIET-004 with two hydroxyl groups. Then DIET-004 and triethyl orthoformate are heated at 170 °C and concentrated to give a residue, which is heated with iodine in chloroform to give olefin DIET-005. Finally, dealkylation of DIET-005 with Py-HCl affords Diethylstilbestrol.
発がん性
Diethylstilbestrol is known to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in humans.
環(huán)境運(yùn)命予測
Diethylstilbestrol is a known teratogen and carcinogen.
Experimental studies using transgenic estrogen receptor
knockout animals suggest that binding and activation of the
estrogen receptor is required to elicit diethylstilbestrol
toxicity. Hence, diethylstilbestrol lesions primarily appear in
tissues enriched with estrogen receptors. Diethylstilbestrol
binds to the estrogen receptor with a very high affinity and
forms a complex with the target tissue. The complex then
internalizes in to the cell and translocates to the nucleus. Once
in the nucleus, diethylstilbestrol may directly bind with the
cellular DNA and cause mutations and unscheduled DNA
synthesis. Diethylstilbestrol is also known to induce
aneuploidy.
ジエチルスチルベストロール 上流と下流の製品情報(bào)
原材料
準(zhǔn)備製品