20-cyano-2-formyl-3-hydroxy-19-norpregna-1,3,5(10),17(20)-tetraen-21-nitrile | 208758-53-6

• 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: 20-cyano-2-formyl-3-hydroxy-19-norpregna-1,3,5(10),17(20)-tetraen-21-nitrile
• 英文别名: 20-cyano-2-formyl-3-hydroxy-19-norpregna-1,3,5(10),17(20)-tetraene-21-nitrile；2-[(8S,9S,13S,14S)-2-formyl-3-hydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-ylidene]propanedinitrile
• CAS: 208758-53-6
• 化学式: C₂₂H₂₂N₂O₂
• 分子量: 346.429
• InChiKey: BRFKOEPNXNNKOJ-KAULMNLWSA-N

物化性质

• 沸点：
  538.4±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  20-cyano-2-formyl-3-hydroxy-19-norpregna-1,3,5(10),17(20)-tetraen-21-nitrile 在 sodium hydride 、 甲酸 、 氯磺酰异氰酸酯 作用下， 以 N,N-二甲基甲酰胺 、 二氯甲烷 为溶剂， 反应 5.0h， 以22%的产率得到17-dicyanomethylidene-estra-1,3,5(10)-trien-[3,2,e]-1',2',3'-oxathiazine-2',2'-dioxide
  参考文献：
  名称：

  Steroidal oxathiazine inhibitors of estrone sulfatase

  摘要：

  The presence of estrone sulfatase in breast tumors and the high levels of circulating estrone sulfate may contribute the major portion of estrogen synthesized locally in breast tissues through conversion of estrone sulfate to estrone by the enzyme. Using inhibitors of estrone sulfatase for the treatment of estrogen-dependent (estrogen receptor positive, ER+) breast cancer could be a very effective therapeutic strategy for the treatment of estrogen-dependent breast tumors in postmenopausal women. Therefore, we designed and synthesized several steroidal 2',3-oxathiazines that inhibit estrone sulfatase and have greatly reduced estrogenic side effects. Our in vitro studies indicate that the oxathiazine compounds have inhibitory activity on estrone sulfatase in MCF-7 human breast cancer cells. These estrone sulfatase inhibitors (ESIs) also inhibit the growth of MCF-7 cells induced by estrone sulfate. In addition, our in vivo experiments demonstrate that our ESIs have moderate antitumor activity against MCF-7 breast cancer xenografts in Balb/c athymic nude mice. The synthesis and biological activity of a number of these unique steroidal ESIs are described. (C) 2002 Elsevier Science Inc. All rights reserved.

  DOI：

  10.1016/s0039-128x(02)00118-6
• 作为产物：
  描述：

  2,6-二甲基吡啶 、 四氯化锡 、 20-cyano-3-hydroxy-19-norpregna-1,3,5(10),17(20)-tetraen-21-nitrile 在 盐酸 、 paraformaldehyde 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 以45%的产率得到20-cyano-2-formyl-3-hydroxy-19-norpregna-1,3,5(10),17(20)-tetraen-21-nitrile
  参考文献：
  名称：

  Steriod inhibitors of estrone sulfatase and associated pharmaceutical

  摘要：

  提供了作为雌酮磺酸酶抑制剂有用的新化合物。这些化合物具有结构式（I）##STR1##其中X和Y，或Y和Z，形成一个氧硫氮二氧杂环或一个二氢氧硫氮二氧杂环，其他各种取代基如本文所定义。还提供了使用式（I）化合物治疗雌激素依赖性疾病的药物组合物和方法。

  公开号：

  US05763432A1

文献信息

• US5763432A
  申请人：——

  公开号：US5763432A

  公开（公告）日：1998-06-09
• US5861388A
  申请人：——

  公开号：US5861388A

  公开（公告）日：1999-01-19
• [EN] STEROID INHIBITORS OF ESTRONE SULFATASE, AND ASSOCIATED PHARMACEUTICAL COMPOSITIONS AND METHODS OF USE<br/>[FR] STEROIDES INHIBITEURS DE L'OESTRONE SULFATASE, COMPOSITIONS PHARMACEUTIQUES ASSOCIEES ET PROCEDES D'UTILISATION
  申请人：SRI INTERNATIONAL

  公开号：WO1998032763A1

  公开（公告）日：1998-07-30

  (EN) Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have structural formula (I), wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Also provided are pharmaceutical compositions and methods for using the compounds of formula (I) to inhibit the enzymatic activity of estrone sulfatase and to treat estrogen-dependent disorders.(FR) La présente invention concerne de nouveaux composés efficaces comme inhibiteurs de l'oestrone sulfatase, composés qui sont représentés par la formule (I) dans laquelle X et Y, ou Y et Z forment un noyau de dioxyde d'oxathiazine ou un noyau de dioxyde dihydro-oxathiazine, les autres différents substituants étant tels que définis dans la description. L'invention présente également des compositions pharmaceutiques et des procédés destinés à l'utilisation des composés de la formule (I) élaborés pour inhiber l'activité enzymatique de l'oestrone sulfatase et traiter les troubles liés aux oestrogènes.
• Steriod inhibitors of estrone sulfatase and associated pharmaceutical
  申请人：SRI International

  公开号：US05763432A1

  公开（公告）日：1998-06-09

  Novel compounds useful as inhibitors of estrone sulfatase are provided. The compounds have the structural formula (I) ##STR1## wherein X and Y, or Y and Z, form an oxathiazine dioxide ring or a dihydro-oxathiazine dioxide ring, and the other various substituents are as defined herein. Pharmaceutical compositions and methods for using the compounds of formula (I) to treat estrogen-dependent disorders are provided as well.

  提供了作为雌酮磺酸酶抑制剂有用的新化合物。这些化合物具有结构式（I）##STR1##其中X和Y，或Y和Z，形成一个氧硫氮二氧杂环或一个二氢氧硫氮二氧杂环，其他各种取代基如本文所定义。还提供了使用式（I）化合物治疗雌激素依赖性疾病的药物组合物和方法。
• Steroidal oxathiazine inhibitors of estrone sulfatase
  作者：Richard H Peters、Wan-Ru Chao、Barbara Sato、Kazuhiko Shigeno、Nurulain T Zaveri、Masato Tanabe

  DOI：10.1016/s0039-128x(02)00118-6

  日期：2003.1

  The presence of estrone sulfatase in breast tumors and the high levels of circulating estrone sulfate may contribute the major portion of estrogen synthesized locally in breast tissues through conversion of estrone sulfate to estrone by the enzyme. Using inhibitors of estrone sulfatase for the treatment of estrogen-dependent (estrogen receptor positive, ER+) breast cancer could be a very effective therapeutic strategy for the treatment of estrogen-dependent breast tumors in postmenopausal women. Therefore, we designed and synthesized several steroidal 2',3-oxathiazines that inhibit estrone sulfatase and have greatly reduced estrogenic side effects. Our in vitro studies indicate that the oxathiazine compounds have inhibitory activity on estrone sulfatase in MCF-7 human breast cancer cells. These estrone sulfatase inhibitors (ESIs) also inhibit the growth of MCF-7 cells induced by estrone sulfate. In addition, our in vivo experiments demonstrate that our ESIs have moderate antitumor activity against MCF-7 breast cancer xenografts in Balb/c athymic nude mice. The synthesis and biological activity of a number of these unique steroidal ESIs are described. (C) 2002 Elsevier Science Inc. All rights reserved.