3-Methoxyestra-3,5(10)-dien-17β-ol | 116168-67-3

• 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-Methoxyestra-3,5(10)-dien-17β-ol
• 英文别名: 3-Methoxyestra-3,5(10)-dien-17beta-ol；(8R,9S,13S,14S,17S)-3-methoxy-13-methyl-1,2,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-ol
• CAS: 116168-67-3
• 化学式: C₁₉H₂₈O₂
• 分子量: 288.43
• InChiKey: OETZBPZIUNCYCM-GFEQUFNTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Methoxyestra-3,5(10)-dien-17β-ol 在 吡啶 、 potassium tert-butylate 、 二甲基二环氧乙烷 、 silver nitrate 作用下， 以 乙醚 、 水 、 丙酮 为溶剂， 反应 13.33h， 生成 2-methoxy-3-oxo-A-homo-1,4,5(10)-estratrien-17β-ol
  参考文献：
  名称：

  Synthesis and Structure−Activity Profiles of A-Homoestranes, the Estratropones

  摘要：

  2-Methoxyestradiol, a mammalian metabolite of estradiol, has reported antiangiogenic activity which has been proposed to be mediated through interaction at the colchicine binding site on the tubulin monomer. Subsequent structure-activity studies of 2-methoxyestradiol have yielded highly potent steroidal inhibitors of tubulin polymerization. In an effort to probe the scope of binding at the colchicine binding site and the nature of the relationship between 2-methoxyestradiol and colchicine, a series of colchicine/2-methoxyestradiol hybrids was synthesized. These A-homoestrane hybrid systems, collectively termed estratropones, possessed an A-ring tropone system with the keto functionality at either the C-2, C-3, or C-4 position of the steroid nucleus. The estratropones were evaluated for their ability to inhibit the polymerization of tubulin using an in vitro purified bovine brain assay. Most of these hybrids inhibit polymerization with greater potency than either of the natural products. The most potent of these congeners possessed an approximate 5-fold enhancement of the activity of colchicine for the inhibition of tubulin polymerization. alpha-Substituents on the tropone ring showed varied effects on the activities for the two classes of estratropones studied in this regard, the C-3 oxo and the C-4 oxo species. The 3-substituted 4-oxoestratropones exhibited antitubulin activity according to Cl approximate to Br > OCH3, whereas the 4-substituted 3-oxoestratropones exhibited activity according to OCH3 > Br approximate to Cl. It is unclear if these substituent factors are purely electronic or steric effects or if the substituent operates indirectly by altering the conformation of the nonplanar troponoid ring. The estratropones represent a new class of tubulin binding agents with potential antiangiogenic utility.

  DOI：

  10.1021/jm970323e
• 作为产物：
  描述：

  (17B)-3-甲氧基雌甾-2,5(10)-二烯-17-醇 在 potassium tert-butylate 作用下， 以 四氢呋喃 、 二甲基亚砜 为溶剂， 反应 10.0h， 以1.30 g的产率得到3-Methoxyestra-3,5(10)-dien-17β-ol
  参考文献：
  名称：

  Synthesis and Structure−Activity Profiles of A-Homoestranes, the Estratropones

  摘要：

  2-Methoxyestradiol, a mammalian metabolite of estradiol, has reported antiangiogenic activity which has been proposed to be mediated through interaction at the colchicine binding site on the tubulin monomer. Subsequent structure-activity studies of 2-methoxyestradiol have yielded highly potent steroidal inhibitors of tubulin polymerization. In an effort to probe the scope of binding at the colchicine binding site and the nature of the relationship between 2-methoxyestradiol and colchicine, a series of colchicine/2-methoxyestradiol hybrids was synthesized. These A-homoestrane hybrid systems, collectively termed estratropones, possessed an A-ring tropone system with the keto functionality at either the C-2, C-3, or C-4 position of the steroid nucleus. The estratropones were evaluated for their ability to inhibit the polymerization of tubulin using an in vitro purified bovine brain assay. Most of these hybrids inhibit polymerization with greater potency than either of the natural products. The most potent of these congeners possessed an approximate 5-fold enhancement of the activity of colchicine for the inhibition of tubulin polymerization. alpha-Substituents on the tropone ring showed varied effects on the activities for the two classes of estratropones studied in this regard, the C-3 oxo and the C-4 oxo species. The 3-substituted 4-oxoestratropones exhibited antitubulin activity according to Cl approximate to Br > OCH3, whereas the 4-substituted 3-oxoestratropones exhibited activity according to OCH3 > Br approximate to Cl. It is unclear if these substituent factors are purely electronic or steric effects or if the substituent operates indirectly by altering the conformation of the nonplanar troponoid ring. The estratropones represent a new class of tubulin binding agents with potential antiangiogenic utility.

  DOI：

  10.1021/jm970323e

文献信息

• Anti-angiogenic agents
  申请人：Allergan Sales, Inc.

  公开号：US06271220B1

  公开（公告）日：2001-08-07

  The application discloses methods of treating mammalian diseases characterized by undesirable angiogenesis by administering compounds including those having the general formulae wherein A is a fused tropone having a general formula: wherein X is selected from the group consisting of hydrogen, hydroxy, carboxy, halogen, nitro, C1 to C12 alkenyl, C1 to C12 alkyl, C1 to C12 alkoxy, SR, NR2, OSO3−, OSO2NR2, HNSO3−, NHSO2NR2, SSO3−, SSO2NR2, wherein R is hydrogen or a C1 to C6 alkyl and the 17-ester and keto derivatives thereof, in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the method of the invention.

  该申请披露了治疗哺乳动物疾病的方法，这些疾病以不良血管生成为特征，通过给予包括具有以下一般式的化合物来实现，其中A是具有以下一般式的融合环戊酮：其中X选自羟基、羟基、羧基、卤素、硝基、C1到C12烯基、C1到C12烷基、C1到C12烷氧基、SR、NR2、OSO3−、OSO2NR2、HNSO3−、NHSO2NR2、SSO3−、SSO2NR2，其中R是氢或C1到C6烷基及其17-酯和酮衍生物，剂量足以抑制细胞有丝分裂。该申请披露了该发明方法中使用的新化合物。
• The synthesis and evaluation of functionalized estratropones: Potent inhibitors of tubulin polymerization
  作者：Thomas A. Miller、Amanda L. Bulman、Charles D. Thompson、Michael E. Garst、Timothy L. Macdonald

  DOI：10.1016/s0960-894x(97)00327-2

  日期：1997.7

  The synthesis of several alpha-substituted estratropones is described. The compounds were evaluated for the inhibition of tubulin polymerization using purified bovine brain tubulin. Several of the compounds are equipotent to colchicine for their ability to inhibit the polymerization of tubulin. (C) 1997 Elsevier Science Ltd.
• US6271220B1
  申请人：——

  公开号：US6271220B1

  公开（公告）日：2001-08-07
• [EN] ANTI-ANGIOGENIC AGENTS<br/>[FR] AGENTS ANTI-ANGIOGENIQUES
  申请人：ALLERGAN SALES, INC.

  公开号：WO1998040077A1

  公开（公告）日：1998-09-17

  (EN) The application discloses methods of treating mammalian diseases characterized by undesirable angiogenesis by administering compounds including those having general formula (1) wherein A is a fused tropone having general formula (I), (II) or (III) wherein X is selected from the group consisting of hydrogen, hydroxy, carboxy, halogen, nitro, C1 to C12 alkenyl, C1 to C12 alkyl, C1 to C12 alkoxy, SR, NR2, OSO3-, OSO2 NR2, HN SO3-, NHSO2NR2, SSO3- SSO2 NR2, wherein R is hydrogen or a C1 to C6 alkyl and the 17-ester and keto derivatives thereof, in a dosage sufficient to inhibit cell mitosis. The application discloses novel compounds used in the method of the invention.(FR) Procédés de traitement de maladies développées par des mammifères, ces maladies se caractérisant par une angiogénèse indésirable et les procédés consistant à administrer des composés de formule (1). Dans cette formule, A représente un tropone fusionné de formule (I), (II) ou (III); X est sélectionné dans le groupe formé par hydrogène, hydroxy, carboxy, halogène, nitro, alcényle C1 à C12, alkyle C1 à C12, alcoxy C1 à C12, SR, NR2, OSO3-, OSO2NR2, HN SO3-, NHSO2NR2, SSO3-, SSO2 NR2; R représentant hydrogène ou un alkyle C1 à C6 et leurs dérivés 17 ester et céto. On administre ces composés suivant un dosage suffisant pour inhiber la mitose cellulaire. On présente également de nouveaux composés utilisés dans le procédé de cette invention.