3,4-Dihydro-6-methoxy-1-(4-methoxybenzoyl)-2(1H)-naphthalenone | 138630-68-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 3,4-Dihydro-6-methoxy-1-(4-methoxybenzoyl)-2(1H)-naphthalenone
• 英文别名: 6-methoxy-1-(4-methoxybenzoyl)-3,4-dihydro-1H-naphthalen-2-one
• CAS: 138630-68-9
• 化学式: C₁₉H₁₈O₄
• 分子量: 310.35
• InChiKey: OPDGUUUMFLEILI-UHFFFAOYSA-N

物化性质

• 沸点：
  503.5±50.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3,4-Dihydro-6-methoxy-1-(4-methoxybenzoyl)-2(1H)-naphthalenone 在 4-二甲氨基吡啶 、 正丁基锂 、 三乙胺 、 乙硫醇 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 <3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl>(4-hydroxyphenyl)methanone
  参考文献：
  名称：

  Antiestrogens. 3. Estrogen receptor affinities and antiproliferative effects in MCF-7 cells of phenolic analogs of trioxifene, [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]phenyl[methanone

  摘要：

  Benzothiophenes 3 and 4, derived from the acrylophenone antiestrogen trioxifene (2), are characterized by high estrogen receptor (ER) affinity and low residual estrogenicity compared to tamoxifen (1a). In order to characterize further the growth suppression mechanism for these structural types we have prepared structural variants of 2 bearing hydroxy groups positioned to maximize ER affinity. Thus, dihydronaphthalenes 5 and 6 and benzofluorenes 7 and 8 were prepared and studied in MCF-7 human breast cancer cells, in comparison with 3 and 4. All compounds were powerful suppressants of cell growth, with 50% inhibition ranging from 4.5 to 160 nM. Greatest potency was seen with diphenols 6 and 8. These compounds had intracellular ER affinities ranging from 0.2 to 4.1% of that of estradiol, suggestive of a potential for partial agonist effects. Simultaneous exposure of cells to 0.1-mu-M concentrations of estradiol and 3 or 4 did not affect the degree of growth inhibition seen with 0.1-mu-M 3 or 4 alone. Partial reversal of inhibition occurred when 0.1-mu-M 5-8 were each accompanied by 0.1-mu-M estradiol. Under these conditions complete reversal of growth inhibition has been found with 1a, 1b, and other triarylethylenes. Calmodulin, a putative target for triarylethylenes, and which is antagonized by 1a, was shown to interact weakly with 7 and 8 and not at all with 3-6. These results suggest that MCF-7 cell growth suppression by 3-8 may be due to interaction with unidentified receptors besides ER and extend earlier findings indicating that events occurring after interaction of these compounds with ER differ from those of triarylethylene antiestrogens.

  DOI：

  10.1021/jm00083a019
• 作为产物：
  描述：

  4-甲氧基-苯甲酸苯酯 、 6-甲氧基-3,4-二氢-1H-2-萘酮 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以57%的产率得到3,4-Dihydro-6-methoxy-1-(4-methoxybenzoyl)-2(1H)-naphthalenone
  参考文献：
  名称：

  Antiestrogens. 3. Estrogen receptor affinities and antiproliferative effects in MCF-7 cells of phenolic analogs of trioxifene, [3,4-dihydro-2-(4-methoxyphenyl)-1-naphthalenyl][4-[2-(1-pyrrolidinyl)ethoxy]phenyl[methanone

  摘要：

  Benzothiophenes 3 and 4, derived from the acrylophenone antiestrogen trioxifene (2), are characterized by high estrogen receptor (ER) affinity and low residual estrogenicity compared to tamoxifen (1a). In order to characterize further the growth suppression mechanism for these structural types we have prepared structural variants of 2 bearing hydroxy groups positioned to maximize ER affinity. Thus, dihydronaphthalenes 5 and 6 and benzofluorenes 7 and 8 were prepared and studied in MCF-7 human breast cancer cells, in comparison with 3 and 4. All compounds were powerful suppressants of cell growth, with 50% inhibition ranging from 4.5 to 160 nM. Greatest potency was seen with diphenols 6 and 8. These compounds had intracellular ER affinities ranging from 0.2 to 4.1% of that of estradiol, suggestive of a potential for partial agonist effects. Simultaneous exposure of cells to 0.1-mu-M concentrations of estradiol and 3 or 4 did not affect the degree of growth inhibition seen with 0.1-mu-M 3 or 4 alone. Partial reversal of inhibition occurred when 0.1-mu-M 5-8 were each accompanied by 0.1-mu-M estradiol. Under these conditions complete reversal of growth inhibition has been found with 1a, 1b, and other triarylethylenes. Calmodulin, a putative target for triarylethylenes, and which is antagonized by 1a, was shown to interact weakly with 7 and 8 and not at all with 3-6. These results suggest that MCF-7 cell growth suppression by 3-8 may be due to interaction with unidentified receptors besides ER and extend earlier findings indicating that events occurring after interaction of these compounds with ER differ from those of triarylethylene antiestrogens.

  DOI：

  10.1021/jm00083a019

文献信息

• Dihydrobenzofluorene compounds, intermediates, compositions and methods
  申请人：Eli Lilly and Company

  公开号：US05792762A1

  公开（公告）日：1998-08-11

  The invention provides dihydronaphthofluorene compounds, formulations, and methods of inhibiting bone loss or bone resorption, particularly osteoporosis, and cardiovascular-related pathological conditions.

  这项发明提供了二氢萘芴衍生物、配方和抑制骨质流失或骨吸收的方法，特别是针对骨质疏松症和心血管相关病理条件。
• Dihydronaphthalene and naphthalene compounds, intermediates, formulations, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0826680A1

  公开（公告）日：1998-03-04

  The instant invention provides dihydronaphthalene and naphthalene compounds, intermediates, formulations, and methods for use in the treatment of bone loss or bone resorption . The dihydronaphthalene compounds have the formula: wherein R1 is -H, -OH, -O(C1-C4 alkyl), -OCO(C1-C6 alkyl), -O-CO-O(C1-C6 alkyl) , -O-CO-Ar, -OSO2(C2-C6 alkyl), -O-CO-OAr, where Ar is optionally substituted phenyl; R2 is -H, -Cl, -F, C1-C4 alkyl, -OH, -O(C1-C4 alkyl), -OCO(C1-C6 alkyl), -O-CO-O(C1-C6 alkyl), -O-CO-Ar,-OSO2(C2-C6 alkyl), or -O-CO-OAr, where Ar is optionally substituted phenyl; R3 and R4 are, independently, R2, with the proviso that both R3 and R4 are not both. hydrogen. R5 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-l-pyrrolidino, 4-morpholino, dimethylamino, diethylamino, diisopropylamino, or 1-hexamethyleneimino; and n is 2 or 3; or a pharmaceutically acceptable salt or solvate thereof.

  本发明提供了用于治疗骨质流失或骨吸收的二氢萘和萘化合物、中间体、制剂和方法。二氢萘化合物具有以下式子： 式中 R1 是-H、-OH、-O(C1-C4 烷基)、-OCO(C1-C6 烷基)、-O-CO-O(C1-C6 烷基)、-O-CO-Ar、-OSO2(C2-C6 烷基)、-O-CO-OAr，其中 Ar 是任选取代的苯基； R2 是-H、-Cl、-F、C1-C4 烷基、-OH、-O(C1-C4 烷基)、-OCO(C1-C6 烷基)、-O-CO-O(C1-C6 烷基)、-O-CO-Ar、-OSO2(C2-C6 烷基)或-O-CO-OAr，其中 Ar 是任选取代的苯基； R3 和 R4 独立地为 R2，但 R3 和 R4 不能同时为氢。 R5 是 1-哌啶基、1-吡咯烷基、甲基-1-吡咯烷基、二甲基-1-吡咯烷基、4-吗啉基、二甲基氨基、二乙基氨基、二异丙基氨基或 1-六亚甲基亚氨基；以及 n 为 2 或 3； 或其药学上可接受的盐或溶液。
• US5958916
  申请人：——

  公开号：——

  公开（公告）日：——
• Dihydronaphthalene and naphthalene compounds, intermediates, formulations, and methods of preparation thereof.
  申请人：ELI LILLY AND COMPANY

  公开号：EP0826680B1

  公开（公告）日：2001-10-24
• Benzofluorene compounds, intermediates, compositions, and methods
  申请人：ELI LILLY AND COMPANY

  公开号：EP0832881B1

  公开（公告）日：2002-04-03