11-<3'-(benzoyloxy)-17'-oxoestra-1',3',5'(10')-trien-7'α-yl>undecanoic acid | 55592-11-5

• 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: 11-<3'-(benzoyloxy)-17'-oxoestra-1',3',5'(10')-trien-7'α-yl>undecanoic acid
• 英文别名: 11-[3'-(benzoyloxy)-17'-oxoestra-1',3',5'(10')-trien-7'α-yl]undecanoic acid；11-[(7R,8R,9S,13S,14S)-3-benzoyloxy-13-methyl-17-oxo-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-7-yl]undecanoic acid
• CAS: 55592-11-5
• 化学式: C₃₆H₄₆O₅
• 分子量: 558.758
• InChiKey: XNDNDMYRWRBUMV-AQRIYETRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  41
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  80.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11-<3'-(benzoyloxy)-17'-oxoestra-1',3',5'(10')-trien-7'α-yl>undecanoic acid 在 sodium hydroxide 、 lithium aluminium tetrahydride 、 次氯酸叔丁酯 、 三正丁胺 、 sodium acetate 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 溶剂黄146 、 丙酮 为溶剂， 反应 22.58h， 生成 EM-170
  参考文献：
  名称：

  新型卤素甾体抗雌激素的合成和生物活性。

  摘要：

  抗雌激素疗法是最广泛使用的内分泌疗法，用于治疗乳腺癌，尤其是绝经后妇女。不幸的是，目前可获得的化合物具有混合的激动/拮抗活性，因此潜在地限制了它们的治疗功效。根据观察发现，在17β-雌二醇的7α位上的脂肪链不会阻止与雌激素受体的结合，而卤化雌二醇可以增加其结合（表示为RBA）对雌激素受体的亲和力，我们合成了一系列新的甾体类抗雌激素药（6-10），在16个α位上同时具有7个α-十一碳酰胺基和一个卤素原子（Cl，Br或I）。这些化合物的立体化学是通过高场（400-MHz）核磁共振确定的。获得的某些化合物具有有效的体内抗雌激素活性。在每天两次的低剂量3微克剂量下，16α-氯3,17β-二醇酰胺，16α-碘3,17β-二醇酰胺，16α-溴3,17β-二醇酰胺，16α-氯3,17α-二醇酰胺和16α-溴3,17α-二醇酰胺分别抑制74％，63％，52％，35％和60％的雌二醇诱导的去卵巢Balb /

  DOI：

  10.1021/jm00109a014
• 作为产物：
  描述：

  3-benzoyloxy 7α-(11'-hydroxy undecyl) estra-1,3,5(10)-trien-17β-ol 在 jones reagent 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 11-<3'-(benzoyloxy)-17'-oxoestra-1',3',5'(10')-trien-7'α-yl>undecanoic acid
  参考文献：
  名称：

  N-Butyl-N-methyl-11-(3'-hydroxy-21',17'-carbolactone-19'-nor-17'α-pregna-1',3',5'(10')-trien-7'α-yl)-undecanamide: an inhibitor of type 2 17β-hydroxysteroid dehydrogenase that does not have oestrogenic or androgenic activity

  摘要：

  It is well known that 17 beta-hydroxysteroid dehydrogenases (17 beta-HSDs) play a key role in the formation and inactivation, from circulating precursors, of several active androgens and oestrogens. These enzymes can thus regulate tumoural cell proliferation in androgen- and oestrogen-dependent cancers. Recently, we discovered that adding a spiro-gamma-lactone to the oestradiol nucleus results in a novel inhibitor of type 2 17 beta-HSD, an enzyme that catalyses the interconversions between 4-androstene-3,17-dione and testosterone, and between oestrone and oestradiol. This finding motivated our introducing the spiro-gamma-lactone moiety onto an anti-oestrogenic nucleus. The N-butyl-N-methyl-11-(3'-hydroxy-21',17'-carbolactone-19'-nor-17'alpha-pregna-1',3',5'(10')-trien-7'alpha-yl)-undecanamide (4) was then efficiently synthesized and its biological activity was assessed in vitro. Despite the presence of a bulky alkylamide side chain, the spiro-gamma-lactone function conserved its ability to inhibit type 2 17 beta-HSD (IC50 = 0.35 and 0.25 mu M, with and without side chain, respectively). Furthermore, the selective inhibition by lactone 4 toward type 2 17 beta-HSD (microsomal fraction of human placenta) was demonstrated by the absence of inhibitory activity toward type 1 17 beta-HSD (cytosolic fraction of human placenta). Cell proliferation assays indicated that compound 4 had no oestrogenic activity but did show anti-oestrogenic activity on ER+ cell line ZR-75-1. No androgenic activity could be detected when assayed on the AR(+) cell Line Shionogi either. Based on these facts, we report the synthesis of a new steroidal derivative, one that inhibits type 2 17 beta-HSD while possessing anti-oestrogenic activity. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00124-0

文献信息

• LEVESQUE, CHARLES;MERAND, YVES;DUFOUR, JEAN-MARC;LABRIE, CLAUDE;LABRIE, F+, J. MED. CHEM., 34,(1991) N, C. 1624-1630
  作者：LEVESQUE, CHARLES、MERAND, YVES、DUFOUR, JEAN-MARC、LABRIE, CLAUDE、LABRIE, F+

  DOI：——

  日期：——