(8R,9S,13S,14S)-3-Chloromethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one | 237390-54-4

• 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: (8R,9S,13S,14S)-3-Chloromethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one
• 英文别名: (8R,9S,13S,14S)-3-(chloromethyl)-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-one
• CAS: 237390-54-4
• 化学式: C₁₉H₂₃ClO
• 分子量: 302.844
• InChiKey: KDXFDEUHTDODLJ-VXNCWWDNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (8R,9S,13S,14S)-3-Chloromethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one 在 N-甲基吡咯烷酮 、 sodium azide 、 三乙胺盐酸盐 作用下， 以 水 、 丙酮 为溶剂， 反应 4.0h， 生成 (8R,9S,13S,14S)-13-Methyl-3-(1H-tetrazol-5-ylmethyl)-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  The difluoromethylene group as a replacement for the labile oxygen in steroid sulfates: a new approach to steroid sulfatase inhibitors

  摘要：

  Several estrone sulfate and estradiol sulfate analogues, in which the sulfate group was replaced with an alpha, alpha-difluoromethylenesulfonate group or an alpha, alpha-difluoromethylenetetrazole group, were examined as inhibitors of steroid sulfatase (STS). These compounds were 4.5-10.5 times more potent than their non-fluorinated analogues. Moreover, the presence of the fluorines changed the mode of inhibition from mixed to competitive. The inhibitor bearing the alpha, alpha-difluoromethylenetetrazole group exhibited an affinity for STS approaching that of the natural STS substrate, estrone sulfate. Possible reasons for the enhanced affinity of the fluorinated compounds compared to their non-fluorinated counterparts are discussed. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.089
• 作为产物：
  描述：

  3-hydroxymethylestra-1,3,5-(10)-triene-17-one 在 四氯化碳 、 三苯基膦 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以96%的产率得到(8R,9S,13S,14S)-3-Chloromethyl-13-methyl-6,7,8,9,11,12,13,14,15,16-decahydro-cyclopenta[a]phenanthren-17-one
  参考文献：
  名称：

  Synthesis of estrone-3-sulfate analogues bearing novel non-hydrolyzable sulfate mimetics

  摘要：

  Estrone sulfate analogues have been prepared in which the sulfate group has been replaced with an alpha,alpha-difluoromethylenesulfonate or alpha,alpha-difluoromethylenetetrazole group. The key step in these syntheses was the electrophilic fluorination of neopentylsulfonate ester and nitrile intermediates with N-fluorobenzenesulfonimide (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)00732-7

文献信息

• COMPOSES UTILES NOTAMMENT POUR LA RADIOTHERAPIE OU L'IMAGERIE DU CANCER
  申请人：Duin, Albert Walter

  公开号：EP0310645A1

  公开（公告）日：1989-04-12
• [EN] COMPOUNDS USEFUL PARTICULARLY FOR RADIOTHERAPY OR IMAGING OF CANCER
  申请人：IRE-CELLTARG S.A.

  公开号：WO1988007986A2

  公开（公告）日：1988-10-20

  (EN) Compound useful particularly for the treatment by targetted radiotherapy or imaging of cancer, characterized in that the compound is comprised of a molecule susceptible of fixing itself or passing close to the DNA of the target cells, said molecule being radiolabelled with iodine 123. The invention also relates to new ligands specific of steroid hormone receivers useful for the targetted therapy or imaging particularly of cancer and presenting a structural base skeleton having the formula (I). According to the invention these ligands comprise particularly a) a hydroxyl or ketone function in position C3; b) a $g(b) chloromethyl function on position C11; c) an $g(a) methyl or vinyl function on position C17 and d) a substituted radioactive iodine on an alkyl or alkenyl group attached to the skeleton, particularly methyl or vinyl.(FR) L'invention a pour objet un composé utile notamment pour le traitement en radiothérapie ciblée ou imagerie du cancer, caractérisé en ce qu'il est constitué par une molécule susceptible de se fixer ou de passer à proximité de l'ADN des cellules cibles, ladite molécule étant radiomarquée à l'iode 123. L'invention concerne également de nouveaux ligands spécifiques de récepteurs d'hormones stéroïdes utiles pour la thérapie ciblée ou l'imagerie notamment du cancer présentant un squelette structurel de base ayant pour formule (I). Selon l'invention, ils comportent notamment a) une fonction hydroxyle ou cétone en position C3, b) une fonction chlorométhyle en $g(b) sur la position C11, c) une fonction vinyle ou méthyle en $g(a) sur la position C17 et, d) un iode radioactif substitué sur un groupement alkyl ou alkényl rattaché au squelette, notamment un méthyle ou un vinyle.
• Synthesis of estrone-3-sulfate analogues bearing novel non-hydrolyzable sulfate mimetics
  作者：Mei-Jin Chen、Scott D. Taylor

  DOI：10.1016/s0040-4039(99)00732-7

  日期：1999.5

  Estrone sulfate analogues have been prepared in which the sulfate group has been replaced with an alpha,alpha-difluoromethylenesulfonate or alpha,alpha-difluoromethylenetetrazole group. The key step in these syntheses was the electrophilic fluorination of neopentylsulfonate ester and nitrile intermediates with N-fluorobenzenesulfonimide (C) 1999 Elsevier Science Ltd. All rights reserved.
• The difluoromethylene group as a replacement for the labile oxygen in steroid sulfates: a new approach to steroid sulfatase inhibitors
  作者：Jennifer Lapierre、Vanessa Ahmed、Mei-Jin Chen、Mehdi Ispahany、J.Guy Guillemette、Scott D Taylor

  DOI：10.1016/j.bmcl.2003.09.089

  日期：2004.1

  Several estrone sulfate and estradiol sulfate analogues, in which the sulfate group was replaced with an alpha, alpha-difluoromethylenesulfonate group or an alpha, alpha-difluoromethylenetetrazole group, were examined as inhibitors of steroid sulfatase (STS). These compounds were 4.5-10.5 times more potent than their non-fluorinated analogues. Moreover, the presence of the fluorines changed the mode of inhibition from mixed to competitive. The inhibitor bearing the alpha, alpha-difluoromethylenetetrazole group exhibited an affinity for STS approaching that of the natural STS substrate, estrone sulfate. Possible reasons for the enhanced affinity of the fluorinated compounds compared to their non-fluorinated counterparts are discussed. (C) 2003 Elsevier Ltd. All rights reserved.