3-methoxy-17β-hydroxy-11-oxo-estra-1,3,5(10),8(9)-tetraene | 17401-32-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 3-methoxy-17β-hydroxy-11-oxo-estra-1,3,5(10),8(9)-tetraene
• 英文别名: 11-Keto-3-methoxy-estra-1,3,5(10),8-tetraen-17beta-ol；(13S,14S,17S)-17-hydroxy-3-methoxy-13-methyl-7,12,14,15,16,17-hexahydro-6H-cyclopenta[a]phenanthren-11-one
• CAS: 17401-32-0
• 化学式: C₁₉H₂₂O₃
• 分子量: 298.382
• InChiKey: WYXWPRWDZBSBBO-IEZWGBDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methoxy-17β-hydroxy-11-oxo-estra-1,3,5(10),8(9)-tetraene 、 烯丙基溴化镁 以 四氢呋喃 、 乙醚 为溶剂， 反应 2.0h， 以74%的产率得到11-allyl-11,17β-dihydroxy-3-methoxy-estra-1,3,5(10),8(9)-tetraene
  参考文献：
  名称：

  Synthesis and in vivo evaluation of 11-substituted estradiol derivatives as anti-implantation agents

  摘要：

  Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17 beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10), 8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg (1). (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.093
• 作为产物：
  描述：

  3,9α,17β-trihydroxyestra-1,3,5(10)-trien-11-one 17-acetate 3-methyl ether 在 高氯酸 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以76%的产率得到3-methoxy-17β-hydroxy-11-oxo-estra-1,3,5(10),8(9)-tetraene
  参考文献：
  名称：

  Synthesis and in vivo evaluation of 11-substituted estradiol derivatives as anti-implantation agents

  摘要：

  Synthesis of 11-substituted estradiol derivatives (12-17) has been carried out by the Grignard reaction with alkyl, allyl, and benzyl halides on 17 beta-hydroxy-3-methoxy-11-oxo-estra-1,3,5(10), 8(9)-tetraene (10). The novel compounds (10 and 12-17) were evaluated for their preliminary post-coital contraceptive (anti-implantation) activity in Sprague-Dawley rats. The tested compounds were administered orally and showed significant anti-implantation activity. Compound 13 is the most potent compound in the series which showed 100% contraceptive efficacy at 1.25 mg kg (1). (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.093

文献信息

• 8 Beta-hydrocarbyl-substituted estratrienes for use as selective estrogens
  申请人：——

  公开号：US20030176405A1

  公开（公告）日：2003-09-18

  This invention describes the new 8&bgr;-substituted estratrienes of general formula I in which R 2 , R 3 , R 6 , R 6′ , R 7 , R 7′ , R 9 , R 11 , R 11′ , R 12 , R 14 , R 15 , R 15′ , R 16 , R 16′ , R 17 and R 17′ have the meanings that are indicated in the description, and R 8 means a straight-chain or branched-chain, optionally partially or completely halogenated alkyl or alkenyl radical with up to 5 carbon atoms, an ethinyl- or prop-1-inyl radical, as pharmaceutical active ingredients that have in vitro a higher affinity to estrogen receptor preparations of rat prostates than to estrogen receptor preparations of rat uteri and in vivo preferably a preferential action on bone rather than the uterus and/or a pronounced action with respect to stimulation of the expression of 5HT2a-receptors and 5HT2a-transporters, their production, their therapeutic use and pharmaceutical dispensing forms that contain the new compounds. The invention also describes the use of these compounds for treatment of estrogen-deficiency-induced diseases and conditions as well as the use of an 8&bgr;-substituted estratriene structural part in the total structures of compounds that have a dissociation in favor of their estrogenic action on bones rather than the uterus.

  本发明描述了新的8&bgr;-取代的环雌三烯通式I，其中R2、R3、R6、R6'、R7、R7'、R9、R11、R11'、R12、R14、R15、R15'、R16、R16'、R17和R17'的含义如说明书所示，而R8表示直链或支链，可选部分或完全卤代的含有最多5个碳原子的烷基或烯基基团，一个乙炔基或丙-1-炔基，作为药物活性成分，具有比大鼠子宫雌激素受体制备更高的亲和力，而且在体内更倾向于对骨骼而不是子宫产生优先作用和/或对5HT2a受体和5HT2a转运体的表达刺激作用显著，本发明还描述了这些化合物的生产、治疗用途和含有新化合物的药物配制形式。本发明还描述了这些化合物用于治疗雌激素缺乏引起的疾病和病症，以及在化合物的总结构中使用8&bgr;-取代的环雌三烯结构部分，以使其更倾向于对骨骼而不是子宫产生雌激素作用的解离。
• 8Beta-Hydrocarbyl-Substituted Estratrienes As Selectively Active Estrogens
  申请人：Peters Olaf

  公开号：US20080182829A1

  公开（公告）日：2008-07-31

  This invention describes the new 8β-substituted estratrienes of general formula I in which R 2 , R 3 , R 6 , R 6′ , R 7 , R 7′ , R 9 , R 11 , R 11′ , R 12 , R 14 , R 15 , R 15′ , R 16 , R 16′ , R 17 , R 17′ have the meanings that are indicated in the description, and R 8 means a straight-chain or branched-chain, optionally partially or completely halogenated alkyl or alkenyl radical with up to 5 carbon atoms, an ethinyl- or prop-1-inyl radical, as pharmaceutical active ingredients that have in vitro a higher affinity to estrogen receptor preparations of rat prostates than to estrogen receptor preparations of rat uteri and in vivo preferably a preferential action on bone rather than the uterus and/or a pronounced action with respect to stimulation of the expression of 5HT2a-receptors and 5HT2a-transporters, their production, their therapeutic use and pharmaceutical dispensing forms that contain the new compounds. The invention also describes the use of these compounds for treatment of estrogen-deficiency-induced diseases and conditions as well as the use of an 8β-substituted estratriene structural part in the total structures of compounds that have a dissociation in favor of their estrogenic action on bones rather than the uterus.

  本发明描述了一种新的8β-取代的雌三烯酮通式I，其中R2、R3、R6、R6′、R7、R7′、R9、R11、R11′、R12、R14、R15、R15′、R16、R16′、R17、R17′具有说明书中所指示的含义，而R8表示直链或支链，可选部分或完全卤代烷基或烯基基团，碳数不超过5个，以太炔基或丙烯基基团，作为具有体外比大鼠前列腺雌激素受体制备亲和力高于大鼠子宫雌激素受体制备的药物活性成分，且在体内优先作用于骨而不是子宫和/或对5HT2a受体和5HT2a转运体的表达刺激具有显著作用，以及它们的生产、治疗用途和包含新化合物的制剂。本发明还描述了这些化合物在治疗雌激素缺乏引起的疾病和病情方面的用途，以及在化合物的总结构中使用8β-取代的雌三烯酮结构部分，以促进它们对骨而不是子宫的雌激素作用的解离。
• 8β-hydrocarbyl-substituted estratrienes for use as selective estrogens
  申请人：Schering Aktiengesellschaft

  公开号：US07378404B2

  公开（公告）日：2008-05-27

  This invention describes the new 8β-substituted estratrienes of general formula I in which R2, R3, R6, R6′, R7, R7′, R9, R11, R11′, R12, R14, R15, R15′, R16, R16′, R17 and R17′ have the meanings that are indicated in the description, and R8 means a straight-chain or branched-chain, optionally partially or completely halogenated alkyl or alkenyl radical with up to 5 carbon atoms, an ethinyl- or prop-1-inyl radical, as pharmaceutical active ingredients that have in vitro a higher affinity to estrogen receptor preparations of rat prostates than to estrogen receptor preparations of rat uteri and in vivo preferably a preferential action on bone rather than the uterus and/or a pronounced action with respect to stimulation of the expression of 5HT2a-receptors and 5HT2a-transporters, their production, their therapeutic use and pharmaceutical dispensing forms that contain the new compounds. The invention also describes the use of these compounds for treatment of estrogen-deficiency-induced diseases and conditions as well as the use of an 8β-substituted estratriene structural part in the total structures of compounds that have a dissociation in favor of their estrogenic action on bones rather than the uterus.

  本发明描述了一种新的8β取代的雌三烯类化合物，其通式为I，其中R2、R3、R6、R6′、R7、R7′、R9、R11、R11′、R12、R14、R15、R15′、R16、R16′、R17和R17′的含义如说明书所示，R8表示直链或支链、可选部分或完全卤代的烷基或烯基基团，其碳原子数不超过5，或乙炔基或丙-1-炔基。这些化合物是一种新型的药物活性成分，其在体外对大鼠前列腺的雌激素受体制备具有比在大鼠子宫的雌激素受体制备更高的亲和力，在体内更倾向于对骨骼而非子宫产生优先作用，并且具有刺激5HT2a受体和5HT2a转运体表达的明显作用。本发明还描述了这些化合物的制备、治疗用途以及含有这些新化合物的药物剂型。本发明还描述了在骨骼而非子宫上的雌激素作用方面优于子宫的化合物中，8β取代的雌三烯类结构部分的使用。这些化合物可用于治疗雌激素缺乏引起的疾病和病况。
• 8.BETA.-HYDROCARBYL-SUBSTITUIERTE ESTRATRIENE ALS SELEKTIV WIRKSAME ESTROGENE
  申请人：Bayer Schering Pharma Aktiengesellschaft

  公开号：EP1272504B1

  公开（公告）日：2007-05-30
• US3990956A
  申请人：——

  公开号：US3990956A

  公开（公告）日：1976-11-09