3-Methoxy-8,14-seco-oestratetraen-(1,3,5(10),9)-ol-(17β)-on-(14) | 171337-12-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 3-Methoxy-8,14-seco-oestratetraen-(1,3,5(10),9)-ol-(17β)-on-(14)
• 英文别名: (2R,3S)-3-hydroxy-2-[(2E)-2-(6-methoxy-3,4-dihydro-2H-naphthalen-1-ylidene)ethyl]-2-methylcyclopentan-1-one
• CAS: 171337-12-5
• 化学式: C₁₉H₂₄O₃
• 分子量: 300.398
• InChiKey: IDICKGLOPKUVSX-OWQTYREESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• 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-8,14-seco-oestratetraen-(1,3,5(10),9)-ol-(17β)-on-(14) 、 乙酸酐 以 吡啶 为溶剂， 反应 12.0h， 以95%的产率得到17β-Acetoxy-3-methoxy-8,14-secoestra-1,3,5(10),9(11)-tetraen-14-on
  参考文献：
  名称：

  Schick, H.; Welzel, H.-P.; Schwarz, S., Journal fur praktische Chemie (Leipzig 1954), 1982, vol. 324, # 4, p. 550 - 556

  摘要：

  DOI：

文献信息

• Process for the selective reduction of a 14, 17-dioxo-8,4-seco-steroid
  申请人：AKZO N.V.

  公开号：EP0069424A1

  公开（公告）日：1983-01-12

  There is provided a process for the selective reduction of 8,14-seco-1,3,5(10),9(11)-oestratetraene-14,17-diones resulting in the corresponding 14,17-ketols with a higher enantioselectivity than obtainable hitherto and a high diastereoselectivity (trans/cis- or cis/trans-ratio) by using a chiral reducing agent consisting of a complex alkali metal aluminiumhydride having the formula M Al(OR1)m(OR2)nH4-m-n, in which M represents an alkali metal; OR is derived from the chiral alcohol (+)-(2S,3R)-4-dimethylamino-3-methyl-1,2-diphenyl-2-butanol or the enantiomer thereof with the (-)-(2R,3S)-configuration; OR2 is derived from an achiral organic hydroxy compound having 1-10 C-atoms; m = 1-3; n = 0-2; and m + n ≤ 3.

  提供了一种选择性还原 8,14-seco-1,3,5(10),9(11)-雌甾-14,17-四烯-14,17-二酮的工艺，该工艺通过使用一种手性还原剂得到相应的 14,17-酮，该还原剂的对映体选择性比迄今为止所能得到的要高，并且具有很高的非对映选择性（反式/顺式或顺式/反式比），该手性还原剂由具有以下式子的复合碱金属铝酸酐组成 M Al(OR1)m(OR2)nH4-m-n，其中 M 代表碱金属； OR 源自手性醇 (+)-(2S,3R)-4-dimethylamino-3-methyl-1,2-diphenyl-2-butanol 或其具有 (-)-(2R,3S)-configuration 的对映体； OR2 来自具有 1-10 个 C 原子的非手性有机羟基化合物； m = 1-3；n = 0-2；且 m + n ≤ 3。
• Cortistatin analogues and syntheses and uses thereof
  申请人：President and Fellows of Harvard College

  公开号：US10273241B2

  公开（公告）日：2019-04-30

  Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the -catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.

  本文提供的是式(A)、(B)、(C)、(D)和(E)化合物、其药学上可接受的盐、季胺盐和 N-氧化物及其药物组合物。 式(A)、(B)、(C)、(D)和(E)化合物可考虑用作治疗多种疾病的药物，例如，包括但不限于与血管生成和CDK8和/或CDK19激酶活性相关的疾病。进一步提供的是使用式（A）、（B）、（C）、（D）或（E）化合物抑制 CDK8 和/或 CDK19 激酶活性的方法、调节 -catenin 通路的方法、调节 STAT1 活性的方法、调节 TGFβ/BMP 通路的方法、调节细胞中 HIF-1-α 活性的方法以及增加 BIM 表达以诱导细胞凋亡的方法。进一步提供 CDK8 和 CDK19 点突变体及其使用方法。
• Cortistatin analogues, syntheses, and uses thereof
  申请人：President and Fellows of Harvard College

  公开号：US10273240B2

  公开（公告）日：2019-04-30

  New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.

  本研究提供了新的可的松化合物及其药学上可接受的盐和药学上可接受的组合物。这些化合物可用于治疗由 CDK8 和/或 CDK19 激酶或一般由 Mediator Complex 介导的疾病。特别是，这些化合物可用于治疗诸如肿瘤、癌症或与血管生成相关的疾病。
• CORTISTATIN ANALOGUES AND SYNTHESES AND USES THEREOF
  申请人：President and Fellows of Harvard College

  公开号：US20170029435A1

  公开（公告）日：2017-02-02

  Provided herein are compounds of Formula (A), (B), (C), (D) and (E), pharmaceutically acceptable salts, quaternary amine salts, and N-oxides thereof, and pharmaceutical compositions thereof. Compounds of Formula (A), (B), (C), (D), and (E) are contemplated useful as therapeutics for treating a wide variety of conditions, e.g., including but not limited to, conditions associated with angiogenesis and with CDK8 and/or CDK19 kinase activity. Further provided are methods of inhibiting CDK8 and/or CDK19 kinase activity, methods of modulating the □-catenin pathway, methods of modulating STAT1 activity, methods of modulating the TGFβ/BMP pathway, methods of modulating HIF-1-alpha activity in a cell, and methods of increasing BIM expression to induce apoptosis, using a compound of Formula (A), (B), (C), (D), or (E). Further provided are CDK8 and CDK19 point mutants and methods of use thereof.
• CORTISTATIN ANALOGUES, SYNTHESES, AND USES THEREOF
  申请人：President and Fellows of Harvard College

  公开号：US20180134725A1

  公开（公告）日：2018-05-17

  New cortistatin compounds and pharmaceutically acceptable salts and pharmaceutically acceptable compositions thereof are provided. These compounds can be used to treat a disorder mediated by CDK8 and/or CDK19 kinase or by the Mediator Complex generally. In particular, the compounds can be used, for example, to treat a disorder such as a tumor, cancer, or a disorder associated with angiogenesis.