estrone | 109613-03-8

• 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: estrone
• 英文别名: (1S,2S,6R,8S,11S,12S,16S)-2-hydroxy-16-methyl-7-oxapentacyclo[9.7.0.02,8.06,8.012,16]octadec-3-ene-5,15-dione
• CAS: 109613-03-8
• 化学式: C₁₈H₂₂O₄
• 分子量: 302.37
• InChiKey: TWKOITGXPNYPJO-PKWAZUJASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  estrone 在 双氧水 、 sodium carbonate 作用下， 以 乙醇 为溶剂， 反应 0.25h， 以63%的产率得到10β-hydroxy-1β,2β,4β,5β-dieepoxyestra-3,17-dione
  参考文献：
  名称：

  Synthesis and antiproliferative activity of epoxy and bromo compounds derived from estrone

  摘要：

  Based on biological properties of epoxyquinols from natural sources, bromo and epoxyquinols derived from estrone were synthesized and screened against Fem-X. HeLa and K-562 cell lines. Evidence was found that the bromine atom and the epoxy moiety significantly increase the antiproliferative activity within the series. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00402-4
• 作为产物：
  描述：

  雌酚酮 在 间氯过氧苯甲酸 、 过氧化苯甲酰 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 24.0h， 以51%的产率得到estrone
  参考文献：
  名称：

  一种新颖的m -CPBA氧化：对苯酚和酚类环氧苯酚

  摘要：

  甾体喹诺醇与顺式环氧喹诺醇一起以50-70％的产率大规模获得。可以调节反应条件，以51-54％的收率仅得到相应的甾族环氧喹醇。

  DOI：

  10.1016/0040-4039(96)00677-6

文献信息

• Steroidal quinols and their use for antioxidant therapy
  申请人：——

  公开号：US20030229060A1

  公开（公告）日：2003-12-11

  The present invention relates to novel estrogen-related steroidal quinols and their use as prodrugs for phenolic estrogens and estrogen analogs. The quinols of the present invention provide improved physicochemical properties, increased bioavailability, and improved distribution into tissues and penetration across the blood-brain barrier when compared to phenolic estrogens and estrogen analogs.

  本发明涉及新型雌激素相关的类固醇醌类化合物，以及它们作为酚类雌激素和雌激素类似物的前药的用途。与酚类雌激素和雌激素类似物相比，本发明的醌类化合物具有改善的物理化学性质、增加的生物利用度以及改善的组织分布和穿越血脑屏障能力。
• The synthesis and biological evaluation of A-ring substituted steroidal p-quinones
  作者：Dragana R. Milić、Miroslav J. Gašić、Wolfgang Muster、János J. Csanádi、Bogdan A. Šolaja

  DOI：10.1016/s0040-4020(97)00910-1

  日期：1997.10

  The preparation of A-ring steroidal 1,4-quinones involves m-CPBA/(BzO)2O/hv oxidation of estrone (or estradiol 17-acetate), acid rearrangement of the obtained quinol, and oxidation. A detailed NMR analysis of 1,4-quinones and their derivatives, as well as the results of preliminary antibacterial and cytotoxicity tests is presented.

  A环甾族1，4-醌的制备涉及雌酮（或雌二醇17-乙酸酯）的m -CPBA /（BzO）2 O / hv氧化，所得喹诺酸的酸重排和氧化。介绍了对1,4-醌及其衍生物的详细NMR分析，以及初步的抗菌和细胞毒性测试结果。
• [EN] 4-(1-(SULFONYL)-1H-INDOL-2-YL)-4-(HYDROXY)-CYCLOHEXA-2,5-DIENONE COMPOUNDS AND ANALOGS THEREOF AS THERAPEUTIC AGENTS<br/>[FR] COMPOSES DE 4-(1-(SULFONYL)-1H-INDOL-2-YL)-4-(HYDROXY)-CYCLOHEXA-2,5-DIENONE ET ANALOGUES DE CEUX-CI UTILISES COMME AGENTS THERAPEUTIQUES
  申请人：CANCER REC TECH LTD

  公开号：WO2004056361A1

  公开（公告）日：2004-07-08

  This invention pertains to certain 4-(1-(sulfonyl)-1H-indol-2-yl)-4-(hydroxy)-cyclohexa-2,5-dienone compounds, and analogs thereof, including compounds of the following formula, which are, inter alia, antiproliferative agents, anticancer agents, and/or thioredoxin/thioredoxin reductase inhibitors: formula (I) wherein: Ar is a 1-(sulfonyl)-1H-indol-2-yl group; the bond marked alpha is independently: (a) a single bond; or: (b) a double bond; the bond marked beta is independently: (a) a single bond; or: (b) a double bond; the group -OR is independently: (a) -OH; (b) an ether group (e.g., -OMe); or: (c) an acyloxy (i.e., reverse ester) group (e.g., -OC(=O)Me); each of R<2>, R<3>, R<5>, and R<6>, is independently a ring substituent and is: (a) H; (b) a monovalent monodentate substituent; or: (c) a ring substituent which, together with an adjacent ring substituent, and together with the ring atoms to which these ring substituents are attached, form a fused ring; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for example, in the treatment of proliferative conditions, (e.g., cancer), and/or conditions mediated by thioredoxin/thioredoxin reductase.

  本发明涉及某些4-(1-(磺酰基)-1H-吲哚-2-基)-4-(羟基)-环己-2,5-二酮化合物及其类似物，包括以下式的化合物，其中这些化合物是抗增殖剂、抗癌剂和/或硫代雷帕敏/硫代雷帕敏还原酶抑制剂：式(I)其中：Ar是1-(磺酰基)-1H-吲哚-2-基；标记为α的键独立地是：(a) 单键；或：(b) 双键；标记为β的键独立地是：(a) 单键；或：(b) 双键；-OR基独立地是：(a) -OH；(b) 一个醚基团（例如，-OMe）；或：(c) 一个酰氧基（即，反酯基）（例如，-OC(=O)Me）；R2、R3、R5和R6中的每一个独立地是一个环取代基，可以是：(a) H；(b) 一价单齿取代基；或：(c) 一个环取代基，与相邻的环取代基一起，以及与这些环取代基连接的环原子一起形成融合环；以及其药学上可接受的盐、酯、酰胺、溶剂合物、水合物和受保护形式。本发明还涉及含有这些化合物的药物组合物，以及这些化合物和组合物的用途，无论是在体外还是体内，例如，在治疗增殖性疾病（例如，癌症）和/或由硫代雷帕敏/硫代雷帕敏还原酶介导的疾病方面。
• Synthesis and antiproliferative activity of A-ring aromatised and conduritol-like steroidal compounds
  作者：Dragana Milić、Tatjana Kop、Zorica Juranić、Miroslav J. Gašić、Bernard Tinant、Gabriella Pocsfalvi、Bogdan A. Šolaja

  DOI：10.1016/j.steroids.2005.07.001

  日期：2005.12

  observed, followed by acid-catalyzed epoxy-ring opening and subsequent double bond migration, giving as a final product Delta(9,11)A-ring aromatized compounds. Synthesis of conduritol-like compounds and structure confirmation by X-ray crystallography of the precursor of steroidal conduritol is also described. In addition, the results of extensive antiproliferative screening against a panel of 60 cancer cell

  报道了使用催化量的 TMSOTf 对甾体醌醇和环氧醌醇进行芳构化的简单方法。除了角 OH 的乙酰化外，酸催化 (TfOH) 二烯酮-苯酚重排发生了“对位”产物，或者在 4 位封闭的情况下，乙酰氧基 1,2-迁移导致“间位”的形成产品。使用环氧喹啉衍生物作为底物，观察到乙酰氧基消除，然后是酸催化的环氧开环和随后的双键迁移，最终产物 Delta(9,11)A 环芳构化化合物。还描述了类 conduritol 化合物的合成和通过 X 射线晶体学对甾体 conduritol 前体的结构确认。此外，
• 4-(1-(sulfonyl)-1h-indol-2-yl)-4-(hydroxy)-cyclohexa-2,5-dienone compounds and analogs thereof as therapeutic agents
  申请人：Stevens Francis Graham Malcolm

  公开号：US20060100265A1

  公开（公告）日：2006-05-11

  This invention pertains to certain 4-(1-(sulfonyl)-1H-indol-2-yl)-4-(hydroxy)-cyclohexa-2,5-dienone compounds, and analogs thereof, including compounds of the following formula, which are, inter alia, antiproliferative agents, anticancer agents, and/or thioredoxin/thioredoxin reductase inhibitors: formula (I) wherein: Ar is a 1-(sulfonyl)-1H-indol-2-yl group; the bond marked α is independently: (a) a single bond; or: (b) a double bond; the bond marked β is independently: (a) a single bond; or: (b) a double bond; the group —OR O is independently: (a) —OH; (b) an ether group (e.g., —OMe); or: (c) an acyloxy (i.e., reverse ester) group (e.g., —OC(═O)Me); each of R 2 , R 3 , R 5 , and R 6 , is independently a ring substituent and is: (a) H; (b) a monovalent monodentate substituent; or: (c) a ring substituent which, together with an adjacent ring substituent, and together with the ring atoms to which these ring substituents are attached, form a fused ring; and pharmaceutically acceptable salts, esters, amides, solvates, hydrates, and protected forms thereof. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, for example, in the treatment of proliferative conditions, (e.g., cancer), and/or conditions mediated by thioredoxin/thioredoxin reductase.

  本发明涉及某些4-(1-(磺酰基)-1H-吲哚-2-基)-4-(羟基)-环己-2,5-二酮化合物及其类似物，包括以下式的化合物，它们是抗增殖剂、抗癌剂和/或硫代还蛋白/硫代还蛋白还原酶抑制剂等：式(I)其中：Ar是1-(磺酰基)-1H-吲哚-2-基；标记为α的键独立地是：(a) 单键；或：(b) 双键；标记为β的键独立地是：(a) 单键；或：(b) 双键；—ORO基团独立地是：(a) -OH；(b) 醚基团（例如，-OMe）；或：(c) 酰氧基（即反酯基）基团（例如，-OC（═O）Me）；R2、R3、R5和R6中的每一个独立地是一个环取代基，并且是：(a) H；(b) 单价单齿取代基；或：(c) 与相邻的环取代基一起，并且与这些环取代基附着的环原子一起形成融合环的环取代基；以及其药学上可接受的盐、酯、酰胺、溶剂化物、水合物和保护形式。本发明还涉及包含这样的化合物的制药组合物，以及这样的化合物和组合物的使用，无论是体外还是体内，例如在治疗增殖性疾病（例如癌症）和/或由硫代还蛋白/硫代还蛋白还原酶介导的疾病中。