8-Chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one | 905829-53-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 8-Chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one
• 英文别名: 9-chloro-6-hydroxy-2-[(1S)-1-hydroxy-3,3-dimethylbutyl]-1-methoxy-8-methyl-10H-benzo[b][1,5]benzodioxocin-12-one
• CAS: 905829-53-0
• 化学式: C₂₂H₂₅ClO₆
• 分子量: 420.89
• InChiKey: BOPAZFILXWYHJJ-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-Chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N-溴代丁二酰亚胺(NBS) 、 copper(l) iodide 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 16.0h， 生成 8-Chloro-10-ethyl-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one
  参考文献：
  名称：

  Dibenzodioxocinones—A new class of CETP inhibitors

  摘要：

  Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.073
• 作为产物：
  描述：

  1-methoxy-8-methyl-6-(3-methylbutoxy)-12-oxo-10H-benzo[b][1,5]benzodioxocine-2-carbaldehyde 在 N-氯代丁二酰亚胺 、 三氯化铁 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 3.0h， 生成 8-Chloro-11-hydroxy-3-((S)-1-hydroxy-3,3-dimethyl-butyl)-4-methoxy-9-methyl-7H-6,12-dioxa-dibenzo[a,d]cycloocten-5-one
  参考文献：
  名称：

  Dibenzodioxocinones—A new class of CETP inhibitors

  摘要：

  Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.073

文献信息

• A Further Improved Synthesis of a Dibenzodioxocinone CETP Inhibitor
  作者：Zhi-Hua Sun、Erkang Fan、Guo-Qiang Lin

  DOI：10.1055/s-0029-1217757

  日期：2009.10

  A newly improved synthesis of a dibenzodioxocinone CETP inhibitor is described. Key features of the synthetic route include a chiral ligand induced alkyl addition to aldehyde and the use of triethylborane for improved selective alkylation of brominated phenyl ring.

  描述了一种新改进的二苯并二噁烷酮 CETP 抑制剂的合成方法。合成路线的关键特点包括一个手性配体诱导的烷基添加到醛上，以及使用三乙基硼烷以改善溴化苯环的选择性烷基化。
• 7H-DIBENZO[B,G][1,5]DIOXOCIN-5-ON-DERIVATE UND IHRE VERWENDUNG
  申请人：Bayer HealthCare AG

  公开号：EP1560630A2

  公开（公告）日：2005-08-10
• [DE] 7H-DIBENZO[B,G][1,5]DIOXOCIN-5-ON-DERIVATE UND IHRE VERWENDUNG<br/>[EN] 7H-DIBENZO[B,G][1,5]DIOXOCIN-5-ONE DERIVATIVES AND USE THEREOF<br/>[FR] DERIVES DE 7H-DIBENZO[B,G][1,5]DIOXOCINE-5-ONE ET LEUR UTILISATION
  申请人：BAYER HEALTHCARE AG

  公开号：WO2004039453A2

  公开（公告）日：2004-05-13

  Die vorliegende Anmeldung betrifft substituierte 7H-Dibenzo[b,g][1,5]dioxocin-5-on-Derivate, Verfahren zu ihrer Herstellung sowie ihre Verwendung in Arzneimitteln, insbesondere als Inhibitoren des Cholesterin-Ester-Transfer-Proteins (CETP) zur Behandlung und/oder Prävention kardiovaskulärer Erkrankungen, insbesondere von Hypolipoproteinämie, Dyslipidämien, Hypertriglyceridämien, Hyperlipidämien und Arteriosklerose.
• Dibenzodioxocinones—A new class of CETP inhibitors
  作者：David Brückner、Frank-Thorsten Hafner、Volkhart Li、Carsten Schmeck、Joachim Telser、Alexandros Vakalopoulos、Gabriele Wirtz

  DOI：10.1016/j.bmcl.2005.05.073

  日期：2005.8

  Derivatives of the natural product 11-hydroxy-3-[(S)-1-hydroxy-3-methylbutyl]-4-methoxy-9-methyl-5H,7H-dibenzo[b,g][1,5]dioxocin-5-one 1 were studied as novel CETP inhibitors. Compound 2 was identified from HTS as a micromolar inhibitor. The compound suffered from very low stability in plasma. Optimisation by partial synthesis started from 1 and led to low-nanomolar inhibitors with good stability in rat plasma. (c) 2005 Elsevier Ltd. All rights reserved.