3-benxyloxy-17,17-ethylenedioxyestra-1,3,5(10)-trien-11β-ol | 64109-83-7

• 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-benxyloxy-17,17-ethylenedioxyestra-1,3,5(10)-trien-11β-ol
• 英文别名: 3-benzyloxy-17,17-ethylenedioxyestra-1,3,5(10)-trien-11β-ol；(8'S,9'S,11'S,13'S,14'S)-13'-methyl-3'-phenylmethoxyspiro[1,3-dioxolane-2,17'-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthrene]-11'-ol
• CAS: 64109-83-7
• 化学式: C₂₇H₃₂O₄
• 分子量: 420.549
• InChiKey: JXIPCQFRPAJUIF-IYMLOVEFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-benxyloxy-17,17-ethylenedioxyestra-1,3,5(10)-trien-11β-ol 生成 (8S,9S,11S,13S,14S)-11-ethoxy-13-methyl-3-phenylmethoxy-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  PETZOLDT, K.;NEEF, G.;EDER, U.

  摘要：

  DOI：
• 作为产物：
  描述：

  11beta-Hydroxyestrone 在 potassium carbonate 、 对甲苯磺酸 作用下， 以 甲醇 、 氯仿 、 苯 为溶剂， 反应 11.0h， 生成 3-benxyloxy-17,17-ethylenedioxyestra-1,3,5(10)-trien-11β-ol
  参考文献：
  名称：

  Nonpolar and Short Side Chain Groups at C-11β of Estradiol Result in Antiestrogens

  摘要：

  We have previously found that esters of 11beta-estradiol carboxylates are transformed from an estrogen into an antiestrogen when the 11beta-side chain is increased in length from four to five non-hydrogen atoms (n greater than or equal to 5). To understand the structural requirements for this transformation and obtain metabolically stable analogues that are not susceptible to esterase cleavage, we have synthesized other compounds having an 11beta-side chain composed of other functional groups: ketones, amides, ethers, and thiono esters. With the exception of amides, which bind poorly to the estrogen receptor (ER), all of these compounds exhibit antiestrogenic action when the side chain length is n greater than or equal to 5. Ethers (n greater than or equal to 5), studied in more detail, inhibit the action of estradiol with either ERalpha or ERbeta. In rat uteri they are estrogen antagonists/weak agonists and decrease the concentration of cholesterol in blood (an hepatic estrogenic action). Thus, these short chain and nonpolar 11beta-analogues of estradiol have tissue specific antiestrogenic/estrogenic actions, characteristics of selective estrogen receptor modulators.

  DOI：

  10.1021/jm049352x

文献信息

• Synthesis of 11α- and 11β-diethylaminoethyl ethers of 17α-ethynylestradiol
  作者：Cecil M. DiNunno、P. Narasimha Rao、Hyun K. Kim

  DOI：10.1039/p19810002401

  日期：——

  The 11α- and 11β-diethylaminoethyl ethers of 17α-ethynylestradol have been prepared from the intermediate alcohols (7a) and (7b) by direct alkylation with 2-N,N-diethylaminoethyl bromide hydrobromide followed by hydrogenolysis, deacetalization, and reaction with lithium acetylide. The two 11-diethylaminoethyl ethers of 17α-ethynylestradiol showed no significant estrogenic, anti-estrogenic, or post-coital

  由中间体醇（7a）和（7b）通过与2-N，N-二乙基氨基乙基溴化氢溴化物直接烷基化，然后进行氢解，脱缩醛反应和与乙炔化锂反应制得的17α-乙炔雌醇的11α-和11β-二乙基氨基乙基醚是由中间体醇（7a）和（7b）制备的。17α-乙炔基雌二醇的两个11-二乙氨基乙基醚没有明显的雌激素，抗雌激素或性交后活性。
• Novel Estradiol Derivatives Labeled with Ru, W, and Co Complexes. Influence on Hormone-Receptor Affinity of Several Organometallic Groups at the 17 Position
  作者：Siden Top、Hassane El Hafa、Anne Vessières、Michel Huché、Jacqueline Vaissermann、Gérard Jaouen

  DOI：10.1002/1521-3765(20021115)8:22<5241::aid-chem5241>3.0.co;2-m

  日期：2002.11.15

  In order to elucidate the extent to which recognition of the estrogen receptor is influenced by addition of an organometallic substituent at the 17alpha position, modification of 17beta-estradiol at this position was carried out by using the organometallic groups -CdropC-(eta(5)-C5H4)RuCp, CH2-(eta(5)-C5H4)RuCp, -CdropC-(eta(5)-C5H4)-W(CO)(3)(Me), -(CdropCCHO)Co-2(CO)(6), and -(CdropCCH(2)OH)CO2(CO)(6). The relative binding affinity (RBA) values for estradiol receptor alpha showed that recognition was good (RBA between 20 and 13.5%) when the organometallic moiety was attached at the end of a rigid alkyne spacer. However, the affinity of the modified hormone for the receptor was severely reduced. (RBA = 1%) for a substituent such as -CH2-(eta(5)-C5H4)-RuCp, in which the spacer is reduced to a single flexible sp(3) carbon atom, allowing the organometallic moiety greater freedom of movement around the attachment point. The RBA values found were in agreement with results obtained from a molecular-modeling study in which 5, an organometallic hormone with a rigid spacer, or 7, a molecule with a flexible spacer, was inserted into the cavity of the recently characterized Ligand-Binding Domain of estrogen receptor alpha.
• Synthesis and biologic activities of 11β-substituted estradiol as potential antiestrogens
  作者：Xiaodong Qian、Yusuf J. Abul-Hajj

  DOI：10.1016/0039-128x(90)90022-4

  日期：1990.5

  The effect of attachment of a dimethylaminoethoxy or a dimethylaminopropoxy group at the 11 beta-position of estradiol (E2) on its relative binding affinity (RBA) to estrogen receptor (ER) and intrinsic biologic activity is described. The binding of 11 beta-[2-(N,N-dimethylamino) ethoxy]estra-1,3,5(10)-triene-3,17 beta-diol (4) and 11 beta-[3-(N,N- dimethylamino)propoxy]estra-1,3,5(10)-triene-3,17 beta-diol (5) to the ER from immature rat uterine tissue was measured relative to that of [3H]E2 by a competitive binding assay. It was found that the 11 beta-substituted E2 analogs have considerably lower RBA to ER than the corresponding parent compound. The intrinsic activity of compounds 4 and 5 were studied in terms of uterotrophic and antiuterotrophic activity. It was found that the uterotrophic activity of these compounds was drastically reduced compared with E2. However, no antiuterotrophic activity was observed in these compounds at dosages ranging from 1 to 100 micrograms/rat/d.
• ZEICHER, M.;QUIVY, J.
  作者：ZEICHER, M.、QUIVY, J.

  DOI：——

  日期：——
• [EN] PHARMACEUTICAL COMPOSITIONS
  申请人：BRITISH TECHNOLOGY GROUP LTD.

  公开号：WO1993012137A1

  公开（公告）日：1993-06-24

  (EN) Compounds of formula (I) in which the dotted line indicates the optional presence of a double bond joining the 6 and 7 positions, A is a divalent group having a chain of at least four atoms joining the oxy group and the group BX, which group A is an aliphatic hydrocarbon group or such a group in which there is replacement by one or more groups selected from formula (1) and phenylene, wherein R is hydrogen or an alkyl group and R' and R'' are the same or different alkyl groups, of one or more carbon atoms, excluding (a) replacement of that carbon atom attached to the group B, (b) replacement of both of any two carbon atoms which are joined either directly or through a single further carbon atom, and, except in the case of the replacement groups (2) and (3), (c) replacement of that carbon atom attached to the oxy group; (B) is selected from formula (4), -COO- and -OCO-, wherein R or each R separately is hydrogen or an alkyl group, X is a sugar residue and Y is hydrogen or an alkyl, alkenyl or alkynyl group, the compound (I) optionally being in the form of a physiologically acceptable ester and/or of a physiologically acceptable salt where appropriate are of value in therapy, for example in the treatment of breast cancer.(FR) Compositions de la formule (I) dans laquelle la ligne pointillée indique la présence éventuelle d'une double liaison réunissant les positions 6 et 7, A représente un groupe bivalent comprenant une chaîne d'au moins quatre atomes réunissant le groupe oxy et le groupe BX, le groupe A représentant un groupe hydrocarbure aliphatique ou un groupe analogue dans lequel a eu lieu une substitution par un ou plusieurs groupes choisis entre la formule (1) et phénylène, R représentant hydrogène ou un groupe alkyle, et R' et R'' représentant des groupes alkyle identiques ou différents, contenant au moins un atome de carbone, à l'exclusion de (a) la substitution de l'atome de carbone accolé au groupe B, (b) la substitution de n'importe quels deux atomes de carbone qui sont réunis soit directement soit par un seul atome de carbone supplémentaire et, sauf dans le cas des groupes de substitution (2) et (3), (c) la substitution de l'atome de carbone accolé au groupe oxy; B est choisi entre la formule (4), -COO- et OCO, où R ou chaque R représentent séparément hydrogène ou un groupe alkyle, X représente un reste de sucre et Y représente hydrogène ou un groupe alkyle, alcényle ou alcynyle. Le composé (I) peut éventuellement se présenter sous forme d'un ester et/ou d'un sel physiologiquement acceptables, comme il convient, ceux-ci présentant une utilité thérapeutique, notamment pour le traitement du cancer du sein.