<3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl>(4-hydroxyphenyl)methanone | 63620-02-0

• 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-hydroxyphenyl)methanone
• 英文别名: (4-Hydroxyphenyl)<3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl>methanone；[3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl](4-hydroxyphenyl)methanone；3-(4-methoxyphenyl)-4-(4-hydroxybenzoyl)-7-methoxy-1,2-dihydronaphthalene；[3,4-Dihydro-2-(4-methoxyphenyl)-6-methoxynaphthalen-1-yl](4-hydroxyphenyl)methanone；(4-Hydroxyphenyl)-[6-methoxy-2-(4-methoxyphenyl)-3,4-dihydronaphthalen-1-yl]methanone
• CAS: 63620-02-0
• 化学式: C₂₅H₂₂O₄
• 分子量: 386.447
• InChiKey: BMYPVFBAFZKROJ-UHFFFAOYSA-N

物化性质

• 沸点：
  597.8±50.0 °C(predicted)
• 密度：
  1.233±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-氯乙基)哌啶盐酸盐 、 <3,4-dihydro-6-methoxy-2-(4-methoxyphenyl)-1-naphthalenyl>(4-hydroxyphenyl)methanone 在 potassium carbonate 作用下， 以 丁酮 为溶剂， 反应 4.0h， 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
• 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 、 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 6.0h， 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

文献信息

• Method for minimizing the uterothrophic effect of tamoxifen and
  申请人：Eli Lilly and Company

  公开号：US05554628A1

  公开（公告）日：1996-09-10

  The present invention provides a method of minimizing the uterotrophic effect of non-steroidal antiestrogen compounds of formula II ##STR1## and wherein the variables are as defined in the specification and 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 ##STR2## wherein the variables are as defined in the specification.

  本发明提供了一种减少非甾体抗雌激素化合物的子宫增生作用的方法，其中该非甾体抗雌激素化合物的化学式为II，变量如规范中所定义，并且其中所述的化合物II被用于妇女治疗或预防乳腺癌，包括同时或顺序给予妇女化合物I的方法，其中化合物I的化学式为I，变量如规范中所定义。
• 1-[4-(Substituted alkoxy)benzyl] naphthalene compounds having estrogen inhibitory activity
  申请人：ELI LILLY AND COMPANY

  公开号：EP0895989A1

  公开（公告）日：1999-02-10

  A class of substituted benzylnaphthylene compounds of the structure where R1 and R2 are independently hydrogen, alkyl of one to six carbon atoms, acyl of two to six carbon atoms, or phenacyl; X is -(CH2)1-6; Y is absent or is selected from 1,4-piperazinylene; ureido; N-(lower alkyl)ureido; N'-(lower alkyl)ureido; or N, N'-(di-lower alkyl ureido; and Z is 1-, 2- or 3-pyrrolidinyl; 1-, 2-, or 3-[1-(lower alkyl) pyrrolidinyl]; 1- 2-,3- or 4-piperidinyl; 1-, 2-, 3- or 4-[1-lower alkyl)piperidinyl]; N,N-dialkyl; 1-azepinyl; 1- or 2-naphthylamino, 4-morpholinyl, dimethyl-4-morpholinyl, 3-azaspiro[5.5]undecan-3-yl; pyrrolidinon-1-yl; unsubstituted phenyl; or phenyl substituted with acyl of two to four carbon atoms, alkyl of one to four carbon atoms, halo, or alkoxy of one to four carbon atoms; with the proviso that n is not 2 or 3 when Z is 1-pyrrolidinyl, 1-piperidinyl, 1-azepinyl, 4-morpholinyl, N,N-dimethylamino or N,N-diethylamino; are selective estrogen receptor modulators useful in the prophylaxis or treatment of breast cancer.

  一类结构如下的取代苄基萘化合物 其中 R1 和 R2 独立地为氢、1-6 个碳原子的烷基、2-6 个碳原子的酰基或苯基；X 为-(CH2)1-6；Y 不存在或选自 1，4-哌嗪基；脲基；N-(低级烷基)脲基；N'-(低级烷基)脲基；或 N，N'-(二低级烷基脲基；且 Z 是 1-、2- 或 3-吡咯烷基；1-、2- 或 3-[1-（低级烷基）吡咯烷基]；1- 2-、3- 或 4-哌啶基；1-、2-、3- 或 4-[1-低级烷基）哌啶基]；N,N-二烷基；1-氮杂环庚基；1-或 2-萘氨基、4-吗啉基、二甲基-4-吗啉基、3-氮杂螺[5.5]十一烷-3-基；吡咯烷-1-基；未取代的苯基；或被 2 至 4 个碳原子的酰基、1 至 4 个碳原子的烷基、卤素或 1 至 4 个碳原子的烷氧基取代的苯基；但当 Z 为 1-吡咯烷基、1-哌啶基、1-氮杂环庚基、4-吗啉基、N,N-二甲基氨基或 N,N-二乙基氨基时，n 不为 2 或 3；是可用于预防或治疗乳腺癌的选择性雌激素受体调节剂。
• Regioselectivity in the Alkaline Thiolate Deprotection of Aryl Methyl Ethers
  作者：Jeffrey A. Dodge、Mark G. Stocksdale、Kennan J. Fahey、C. David Jones

  DOI：10.1021/jo00108a046

  日期：1995.2
• Dodge Jeffrey A., Stocksdale Mark G., Fahey Kennan J., Jones C. David, J. Org. Chem, 60 (1995) N 3, S 739-741
  作者：Dodge Jeffrey A., Stocksdale Mark G., Fahey Kennan J., Jones C. David

  DOI：——

  日期：——
• Benzo(a)fluorene compounds
  申请人：ELI LILLY AND COMPANY

  公开号：EP0524742B1

  公开（公告）日：1996-02-28