<3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl><4-<2-(1-piperidinyl)ethoxy>phenyl>methanone | 138630-76-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: <3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl><4-<2-(1-piperidinyl)ethoxy>phenyl>methanone
• 英文别名: [3,4-Dihydro-2-(4-methoxyphenyl)-6-methoxynaphthalen-1-yl][4-[2-(1-piperidinyl)ethoxy]phenyl]methanone；3-(4-methoxyphenyl)-4-[4-[2-(piperid-1-yl)ethoxy]benzoyl]-7-methoxy-1,2-dihydronaphthalene；3-(4-methoxyphenyl)-4-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-7-methoxy-1,2-dihydronaphthalene；[3,4-Dihydro-2-(4-methoxyphenyl)-6-methoxynaphthalen-1-yl][4-[2-(1-piperdinyl)ethoxy]phenyl]methanone；[2-(4-Methoxyphenyl)-3,4-dihydro-6-methoxynaphth-1-yl][4-(1-piperidinyl-2-ethoxy) phenyl] methanone；[6-methoxy-2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]-[4-(2-piperidin-1-ylethoxy)phenyl]methanone
• CAS: 138630-76-9
• 化学式: C₃₂H₃₅NO₄
• 分子量: 497.634
• InChiKey: FMNWSASOWARPII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  <3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl><4-<2-(1-piperidinyl)ethoxy>phenyl>methanone 、 Lithium aluminium hydride 在 氮气 、 水 、 乙酸乙酯 、 Sodium sulfate-III 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 [2-(4-Methoxyphenyl)-3,4-dihydro-6-methoxylnaphth-1-yl][4-(1-piperidinyl-2-ethoxy)phenyl]carbinol
  参考文献：
  名称：

  Tetrahydrobenzo\x9ba!fluorene compounds and methods of use

  摘要：

  该发明提供了四氢苯并\x9ba!芴化合物、配方和抑制骨质流失或骨吸收的方法，尤其是对于骨质疏松症和与心血管相关的病理状况，包括高脂血症。

  公开号：

  US05821253A1
• 作为产物：
  描述：

  4-甲氧基-苯甲酸苯酯 在 4-二甲氨基吡啶 、 正丁基锂 、 sodium hydride 、 potassium carbonate 、 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 、 丁酮 为溶剂， 反应 10.0h， 生成 <3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl><4-<2-(1-piperidinyl)ethoxy>phenyl>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

文献信息

• Compositions for minimizing the uterotrophic effect of tamoxifen and its analogs
  申请人：ELI LILLY AND COMPANY

  公开号：EP0702961A2

  公开（公告）日：1996-03-27

  The present invention provides a method of minimizing the uterotrophic effect of non-steroidal antiestrogen compounds of formula II wherein    either R⁴ is H or a lower alkyl radical and R⁵ is a lower alkyl radical, or R⁴ and R⁵ are joined together with the adjacent nitrogen atom to form a heterocyclic radical;    R⁶ is H or a lower alkyl radical;    R⁷ is H, halo, OH, a lower alkyl radical, or is a buta-1,3-dienyl radical which together with the adjacent benzene ring forms a naphthyl radical;    R⁸ is H or OH; and    n is 2;    or a pharmaceutically acceptable salt thereof, wherein said formula II compound is administered to a woman for the treatment or prevention of breast carcinoma, comprising concurrently or sequentially administering to said woman a compound of formula I wherein    R¹ is -H, -OH, -O(C₁-C₄ alkyl), -OCOC₆H₅, -OCO(C₁-C₆ alkyl), or -OSO₂(C₄-C₆ alkyl);    R is -H, -OH, -O(C₁-C₄ alkyl), -OCOC₆H₅, -OCO(C₁-C₆ alkyl), or -OSO₂(C₄-C₆ alkyl);    n is 2 or 3; and    R³ is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof. The present invention further provides pharmaceutical compositions comprising a compound of formula I and a compound of formula II together with a pharmaceutically acceptable carrier, excipient, or diluent.

  本发明提供了一种将式 II 的非类固醇抗雌激素化合物的子宫营养作用降至最低的方法 其中 R⁴ 是 H 或低级烷基，R⁵ 是低级烷基，或者 R⁴ 和 R⁵ 与相邻的氮原子连接在一起形成杂环基； R⁶ 是 H 或低级烷基； R⁷ 是 H、卤素、OH、低级烷基，或者是丁-1,3-二烯基，与邻近的苯环一起形成萘基； R⁸ 是 H 或 OH；以及 n 是 2； 或其药学上可接受的盐，其中所述式 II 化合物用于妇女治疗或预防乳腺癌，包括同时或依次向所述妇女施用式 I 化合物 其中 R¹是-H、-OH、-O(C₁-C₄烷基)、-OCOC₆H₅、-OCO(C₁-C₆烷基)或-OSO₂(C₄-C₆烷基)； R 是-H、-OH、-O(C₁-C₄ 烷基)、-OCOC₆H₅、-OCO(C₁-C₆ 烷基)或-OSO₂(C₄-C₆ 烷基)； n 是 2 或 3；以及 R³ 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、二乙基氨基或 1-六亚甲基亚氨基； 或其药学上可接受的盐。 本发明进一步提供了药物组合物，其包含式 I 化合物和式 II 化合物以及药学上可接受的载体、赋形剂或稀释剂。
• Bicyclic bradykinin receptor antagonists
  申请人：ELI LILLY AND COMPANY

  公开号：EP0707852A2

  公开（公告）日：1996-04-24

  This invention also provides methods for treating or preventing conditions associated with an excess of bradykinins which methods comprise administration of one or more of the substituted indoles, benzofurans, or benzothiophenes described in this invention.

  本发明还提供了治疗或预防与缓激肽过量有关的疾病的方法，这些方法包括施用一种或多种本发明所述的取代吲哚、苯并呋喃或苯并噻吩。
• Compositions for treating resistant tumors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0709090A2

  公开（公告）日：1996-05-01

  The present invention provides methods for reversing multidrug resistance in a resistant neoplasm by treating a mammal in need of said treatment with a substituted indole, benzofuran, benzothiophene, naphthalene, or dihydronaphthalene. This invention also provides methods for treating neoplasms in a mammal which comprises administering to a mammal in need of this treatment a substituted indole, benzofuran, benzothiophene, naphthalene, or dihydronaphthalene in combination with an oncolytic agent.

  本发明提供了通过用取代的吲哚、苯并呋喃、苯并噻吩、萘或二氢萘处理需要所述处理的哺乳动物来逆转耐药性肿瘤的多药耐药性的方法。本发明还提供了治疗哺乳动物肿瘤的方法，其中包括向需要治疗的哺乳动物施用取代的吲哚、苯并呋喃、苯并噻吩、萘或二氢萘，并与溶瘤剂结合使用。
• Preparations for inhibiting mammalian breast carcinoma with tamoxifen and analogs thereof, and certain naphthyl compounds
  申请人：ELI LILLY AND COMPANY

  公开号：EP0702962A2

  公开（公告）日：1996-03-27

  The present invention provides a method of inhibiting hormone-dependent breast carcinoma in a mammal comprising administering to said mammal in need of treatment an effective amount of a first component which is a compound of formula I wherein    R¹ is -H, -OH, -O(C₁-C₄ alkyl), -OCOC₆H₅, -OCO(C₁-C₆ alkyl), or -OSO₂(C₄-C₆ alkyl);    R is -H, -OH, -O(C₁-C₄ alkyl), -OCOC₆H₅, -OCO(C₁-C₆ alkyl), or -OSO₂(C₄-C₆ alkyl);    n is 2 or 3; and    R³ is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof, and an effective amount of a second component which is a compound of formula II wherein    either R⁴ is H or a lower alkyl radical and R⁵ is a lower alkyl radical, or R⁴ and R⁵ are joined together with the adjacent nitrogen atom to form a heterocyclic radical;    R⁶ is H or a lower alkyl radical;    R⁷ is H, halo, OH, a lower alkyl radical, or is a buta-1,3-dienyl radical which together with the adjacent benzene ring forms a naphthyl radical;    R⁸ is H or OH; and    n is 2; or a pharmaceutically acceptable salt thereof.

  本发明提供了一种抑制哺乳动物体内激素依赖性乳腺癌的方法，该方法包括向所述需要治疗的哺乳动物施用有效量的第一组分，该组分是式 I 的化合物 其中 R¹是-H、-OH、-O(C₁-C₄烷基)、-OCOC₆H₅、-OCO(C₁-C₆烷基)或-OSO₂(C₄-C₆烷基)； R 是-H、-OH、-O(C₁-C₄ 烷基)、-OCOC₆H₅、-OCO(C₁-C₆ 烷基)或-OSO₂(C₄-C₆ 烷基)； n 是 2 或 3；以及 R³ 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、二乙基氨基或 1-六亚甲基亚氨基； 或其药学上可接受的盐，以及有效量的第二种成分，即式 II 的化合物 其中 R⁴ 是 H 或低级烷基，R⁵ 是低级烷基，或 R⁴ 和 R⁵ 与相邻的氮原子连接形成杂环基； R⁶ 是 H 或低级烷基； R⁷ 是 H、卤素、OH、低级烷基，或者是丁-1,3-二烯基，与邻近的苯环一起形成萘基； R⁸ 是 H 或 OH；以及 n 是 2； 或其药学上可接受的盐。
• Compositions for inhibiting neuropeptide y receptors
  申请人：ELI LILLY AND COMPANY

  公开号：EP0716854A2

  公开（公告）日：1996-06-19

  This invention provides methods for treating or preventing a condition associated with an excess of neuropeptide Y which methods comprise administration of one or more substituted benzofurans, benzothiophenes or indoles.

  本发明提供了治疗或预防与神经肽 Y 过量有关的疾病的方法，这些方法包括施用一种或多种取代的苯并呋喃、苯并噻吩或吲哚。