3,4-二氢-6-甲氧基-2-苯基-1-[4-(苯基甲氧基)苯基]萘 | 308812-06-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 3,4-二氢-6-甲氧基-2-苯基-1-[4-(苯基甲氧基)苯基]萘
• 中文别名: N-Boc-DL-蛋氨酸
• 英文名称: 4-(4-(benzyloxy)phenyl)-7-methoxy-3-phenyl-1,2-dihydronaphthalene
• 英文别名: 7-methoxy-3-phenyl-4-(4-phenylmethoxyphenyl)-1,2-dihydronaphthalene
• CAS: 308812-06-8
• 化学式: C₃₀H₂₆O₂
• 分子量: 418.535
• InChiKey: GXAWUBYOPVAHKZ-UHFFFAOYSA-N

物化性质

• 熔点：
  105-107°C
• 沸点：
  570.3±50.0 °C(Predicted)
• 密度：
  1.154±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（微溶，加热）、乙酸乙酯（微溶，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-二氢-6-甲氧基-2-苯基-1-[4-(苯基甲氧基)苯基]萘 在 palladium dihydroxide 氢气 作用下， 以 乙醇 为溶剂， 生成 cis-4-(1,2,3,4-tetrahydro-6-methoxy-2-phenyl-1-naphthalenyl)phenol
  参考文献：
  名称：

  Estrogen receptor ligands. Part 14: Application of novel antagonist side chains to existing platforms

  摘要：

  Two novel side chains which had previously been found to enhance antagonist activity in the dihydrobenzoxathiin SERM series were applied to three existing platforms. The novel side chains did not improve the antagonist activity of the existing platforms. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.084
• 作为产物：
  描述：

  magnesium,phenylmethoxybenzene,bromide 在 四(三苯基膦)钯 作用下， 以 四氢呋喃 为溶剂， 生成 3,4-二氢-6-甲氧基-2-苯基-1-[4-(苯基甲氧基)苯基]萘
  参考文献：
  名称：

  Estrogen receptor ligands. Part 14: Application of novel antagonist side chains to existing platforms

  摘要：

  Two novel side chains which had previously been found to enhance antagonist activity in the dihydrobenzoxathiin SERM series were applied to three existing platforms. The novel side chains did not improve the antagonist activity of the existing platforms. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.08.084

文献信息

• [EN] ANTIESTROGEN COMPOUNDS<br/>[FR] COMPOSÉS ANTI-OESTROGÈNE
  申请人：SHARMA ABHISHEK

  公开号：WO2019241231A1

  公开（公告）日：2019-12-19

  A genus of proteolysis-targeting chimeras (PROTACs)-type compounds/antiestrogens has now been found that act as selective estrogen receptor degraders (SERDs) and estrogen receptor antagonists by degrading and antagonizing ERa in breast cancer cells. The compounds are of the following genus: The compounds described herein exhibit anti-proliferative effects, and are potentially useful, alone or in combination with other therapies, for the treatment of breast cancer. In general, these compounds combine a tight binding ERa targeting ligand tethered to a recognition motif or degron. Once bound, the degron recruits destructive cellular components and the targeted receptor (i.e., ERa) is degraded (i.e., destroyed) or antagonized.

  一种蛋白水解靶向嵌合物（PROTACs）类化合物/抗雌激素现已被发现，其作为选择性雌激素受体降解物（SERDs）和雌激素受体拮抗剂，通过在乳腺癌细胞中降解和拮抗ERa发挥作用。这些化合物属于以下类别：本文描述的化合物展示了抗增殖效果，并且可能单独或与其他疗法结合使用，用于乳腺癌的治疗。总的来说，这些化合物将紧密结合的ERa靶向配体与识别基序或降解标记相结合。一旦结合，降解标记将招募破坏性细胞组分，从而降解（即破坏）或拮抗目标受体（即ERa）。
• METHOD FOR THE PREPARATION OF LASOFOXIFENE
  申请人：Lustig Petr

  公开号：US20100256394A1

  公开（公告）日：2010-10-07

  A method of preparing (−)-cis-(5R,6S)-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol D-tartrate-lasofoxifene of formula 1, comprising the following steps a) Preparation of cis-1-2-[4-(2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)-phenoxy]ethyl}pyrrolidine of formula (3) by alkylation of cis-1-(4-hydroxyphenyl)-2-phenyl-6-methoxy-1,2,3,4-tetrahydronaphthalene with 1-(2-chloroethyl)pyrrolidine base or its salt, b) Deprotection of the hydroxyl group in the substance of formula (3) by the effect of hydrobromic acid generating cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol hydrobromide of formula (2a), c) Conversion of the substance of formula (2a) into cis-6-phenyl-5-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-5,6,7,8-tetrahydronaphthalen-2-ol of formula (2b), d) Preparation of lasofoxifene of formula (1) by conversion into the corresponding diasteroisomer by reaction with D-tartaric acid and crystallization.

  制备(−)-顺式-(5R,6S)-6-苯基-5-[4-(2-吡咯烷-1-基乙氧)苯基]-5,6,7,8-四氢萘-2-醇D-酒石酸盐-拉索福辛的方法，包括以下步骤：a）通过将顺式-1-2-[4-(2-苯基-6-甲氧基-1,2,3,4-四氢萘-1-基)-苯氧基]乙基}吡咯烷的式（3）与1-(2-氯乙基)吡咯烷碱或其盐烷基化，制备式（3）的化合物；b）通过氢溴酸作用去保护式（3）中的羟基，生成式（2a）的顺式-6-苯基-5-[4-(2-吡咯烷-1-基乙氧)苯基]-5,6,7,8-四氢萘-2-醇氢溴酸盐；c）将式（2a）的化合物转化为式（2b）的顺式-6-苯基-5-[4-(2-吡咯烷-1-基乙氧)苯基]-5,6,7,8-四氢萘-2-醇；d）通过与D-酒石酸反应并结晶，将化合物转化为相应的对映异构体，制备式（1）的拉索福辛。
• Process for cis-1{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy] ethyl}pyrrolidine
  申请人：——

  公开号：US20020042524A1

  公开（公告）日：2002-04-11

  This invention provides an improved process for cis-1-{2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine which is an intermediate for the preparation of (−)cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol which is useful for the treatment of osteoporosis.

  这项发明提供了一种改进的过程，用于制备cis-1-（2-4-（6-甲氧基-2-苯基-1,2,3,4-四氢萘基）苯氧）乙基吡咯烷，该化合物是制备（-）cis-6-苯基-5-（4-（2-吡咯烷基）乙氧基）苯基-5,6,7,8-四氢萘酚的中间体，该化合物可用于治疗骨质疏松症。
• Process for cis-1- 2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl pyrrolidine
  申请人：Pfizer Products Inc.

  公开号：EP1055658A2

  公开（公告）日：2000-11-29

  This invention provides an improved process for cis-1-2-[4-(6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphthalen-1-yl)phenoxy]ethyl}pyrrolidine of following formula: which is an intermediate for the preparation of (-)cis-6-phenyl-5-[4-(2-pyrrolidin-1-yl-ethoxy)phenyl]-5,6,7,8-tetrahydronaphthalene-2-ol which is useful for the treatment of osteoporosis.

  本发明提供了一种下式的顺式-1-2-[4-(6-甲氧基-2-苯基-1,2,3,4-四氢萘-1-基)苯氧基]乙基}吡咯烷的改进工艺： 是制备(-)顺式-6-苯基-5-[4-(2-吡咯烷-1-基乙氧基)苯基]-5,6,7,8-四氢萘-2-醇的中间体，可用于治疗骨质疏松症。
• ANTIESTROGEN COMPOUNDS
  申请人：SHARMA Abhishek

  公开号：US20210130320A1

  公开（公告）日：2021-05-06

  A genus of proteolysis-targeting chimeras (PROTACs)-type compounds/antiestrogens has now been found that act as selective estrogen receptor degraders (SERDs) and estrogen receptor antagonists by degrading and antagonizing ERa in breast cancer cells. The compounds are of the following genus: The compounds described herein exhibit anti-proliferative effects, and are potentially useful, alone or in combination with other therapies, for the treatment of breast cancer. In general, these compounds combine a tight binding ERa targeting ligand tethered to a recognition motif or degron. Once bound, the degron recruits destructive cellular components and the targeted receptor (i.e., ERa) is degraded (i.e., destroyed) or antagonized.