116057-75-1
116057-75-1 結(jié)構(gòu)式
基本信息
艾多昔芬
化合物 T14883
SB 223030
IDOXIFENE
iodoxifene
(e)-pyrrolidin
IDOXIFENE USP/EP/BP
pyrrolidino-4-iodotamoxifen
(e)-1-(2-(4-(1-(4-iodophenyl)-2-phenyl-1-butenyl)phenoxy)ethyl)pyrrolidine
(E)-1-(2-(4-(1-(4-Iodophenyl)-2-phenylbut-1-en-1-yl)phenoxy)ethyl)pyrrolidine
1-[2-[4-[(1E)-1-(4-Iodophenyl)-2-phenyl-1-buten-1-yl]phenoxy]ethyl]pyrrolidine
物理化學(xué)性質(zhì)
常見(jiàn)問(wèn)題列表
第一個(gè)上市的雌激素受體調(diào)節(jié)劑,禮萊的雷洛昔芬(ralox ifene)可廣泛用于激素替代療法的緩解,但用于控制骨質(zhì)疏松效果不令人滿意。SB公司認(rèn)為,放棄艾多昔芬對(duì)骨質(zhì)疏松的治療研究原因在于經(jīng)過(guò)1年來(lái)的Ⅲ 期臨床試驗(yàn)的安全性評(píng)估,發(fā)現(xiàn)有婦科癥狀副作用,這些癥狀有子宮內(nèi)膜增厚、骨盆腔腹垂和息肉。子宮內(nèi)膜增厚表現(xiàn)在基底細(xì)胞層而不是腺細(xì)胞層。腺細(xì)胞層增厚多與子宮癌有關(guān)。1998年,諾沃-諾德大公司也是因?yàn)椴∪说淖訉m內(nèi)膜增厚而放棄了雌激素受體調(diào)節(jié)劑左美洛昔芬(levormeloxifene)的Ⅲ期臨床研究。盡管還未發(fā)現(xiàn)雷洛昔芬有子宮內(nèi)膜增厚作用,但是,最近艾多昔芬的研究結(jié)果表明這一類藥物可能具有對(duì)子宮內(nèi)膜的作用。
以上信息是由Chemicalbook的東方編輯整理。（2016-02-01）
以苯酚為起始原料,經(jīng)溴化、O-烴化、N-烴化制得7，如下圖所示：
由1-[2-(4-溴苯氧基)乙基]吡咯烷(2)與鎂反應(yīng)得相應(yīng)的格氏試劑，再與關(guān)鍵中間體1-(4-碘苯基)-2-苯基-1-丁酮(1)進(jìn)行格氏反應(yīng)，水解得1-(4-碘苯基)-1-[4-[(2-吡咯烷基)乙氧基]苯基]-2-苯基-1-丁醇，脫水，純化得艾多昔芬。該路線已申請(qǐng)了中國(guó)專利，并得到受理。如下圖所示：
Estrogen receptor
Idoxifene possesses the protective roles in vascular smooth muscle cells by its blunting the angiotensin II-induced production of reactive oxygen species (ROS). Idoxifene evidently suppresses HSC activation, inhibits culture-activated HSC proliferation in a dose-dependent manner, and induces culture-activated HSC apoptosis in a time-dependent manner. Idoxifene acts in bone as an estrogen agonist for osteoblasts, and shows negligible agonist activity in human endometrial cells. Idoxifene and E2 protect hepatocytes from inflammatory cell injury by inhibiting activation of the NF-κB proinflammatory transcription factor.
Animals receive daily intraperitoneal injections of Estradiol (0.5 mg/kg) and an oral gavage of Idoxifene (0.02, 0.1, and 0.5 mg/kg) for 3 days after Dimethylnitrosamine (DMN) treatment. The blood levels of LDH and Estradiol (E2) and histological grades (scores 0 to 5) of liver zone 3 necrosis are evaluated. Idoxifene at doses of over 0.1 mg/kg significantly reduces the hepatic levels of collagen and MDA in the DMN model in a dose-dependent manner. Although Idoxifene and E2 are administered by different routes, i.e., by oral ingestion and intraperitoneal injection, respectively, the antifibrotic effect of a dose of 0.5 mg/kg of Idoxifene is somewhat greater than that of the same dose of E2.