(4-Hydroxyphenyl)<3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl>methanone | 138630-73-6

• 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: (4-Hydroxyphenyl)<3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl>methanone
• 英文别名: <3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl>(4-hydroxyphenyl)methanone；[3,4-Dihydro-2-phenyl-6-methoxynaphthalen-1-yl](4-hydroxyphenyl)methanone；(4-Hydroxyphenyl)-(6-methoxy-2-phenyl-3,4-dihydronaphthalen-1-yl)methanone
• CAS: 138630-73-6
• 化学式: C₂₄H₂₀O₃
• 分子量: 356.421
• InChiKey: YLEXLAKMKSNQFE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4-Hydroxyphenyl)<3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl>methanone 在 甲烷磺酸 作用下， 反应 72.0h， 以23%的产率得到4-(3,9-dimethoxy-11H-benzofluoren-11-yl)phenol
  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 (4-Hydroxyphenyl)<3,4-dihydro-6-methoxy-2-phenyl-1-naphthalenyl>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

• Naphthyl compounds, intermediates, processes, compositions, and method
  申请人：Eli Lilly and Company

  公开号：US05484795A1

  公开（公告）日：1996-01-16

  The present invention provides a compound of formula I ##STR1## wherein R.sup.1 is --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl); R.sup.2 is --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl) or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl); n is 2 or 3; and R.sup.3 is 1-piperidinyl, 1-pyrrolidinyl, methyl-1-pyrrolidinyl, dimethyl-1-pyrrolidinyl, 4-morpholino, dimethylamino, diethylamino, or 1-hexamethyleneimino; or a pharmaceutically acceptable salt thereof, for treating restenosis.

  本发明提供了一种化合物，其化学式为I，其中R.sup.1为--H、--OH、--O(C.sub.1 -C.sub.4烷基)、--OCOC.sub.6 H.sub.5、--OCO(C.sub.1 -C.sub.6烷基)或--OSO.sub.2(C.sub.4 -C.sub.6烷基)；R.sup.2为--H、--OH、--O(C.sub.1 -C.sub.4烷基)、--OCOC.sub.6 H.sub.5、--OCO(C.sub.1 -C.sub.6烷基)或--OSO.sub.2(C.sub.4 -C.sub.6烷基)；n为2或3；R.sup.3为1-哌啶基、1-吡咯基、甲基-1-吡咯基、二甲基-1-吡咯基、4-吗啉基、二甲胺基、二乙胺基或1-己亚甲基氨基；或其药学上可接受的盐，用于治疗再狭窄。
• 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。
• Method for inhibiting mammalian breast carcinoma with tamoxifen, and
  申请人：Eli Lilly and Company

  公开号：US05658931A1

  公开（公告）日：1997-08-19

  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 ##STR1## wherein R.sup.1 is --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl); R.sup.2 is --H, --OH, --O(C.sub.1 -C.sub.4 alkyl), --OCOC.sub.6 H.sub.5, --OCO(C.sub.1 -C.sub.6 alkyl), or --OSO.sub.2 (C.sub.4 -C.sub.6 alkyl); n is 2 or 3; and R.sup.3 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 ##STR2## wherein either R.sup.4 is H or a lower alkyl radical and R.sup.5 is a lower alkyl radical, or R.sup.4 and R.sup.5 are joined together with the adjacent nitrogen atom to form a heterocyclic radical; R.sup.6 is H or a lower alkyl radical; R.sup.7 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; R.sup.8 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激素依赖性乳腺癌的方法，包括向需要治疗的哺乳动物中投与有效量的第一组分，该组分是式I的化合物： 其中，R1为--H、--OH、--O（C1-C4烷基）、--OCOC6H5、--OCO（C1-C6烷基）或--OSO2（C4-C6烷基）；R2为--H、--OH、--O（C1-C4烷基）、--OCOC6H5、--OCO（C1-C6烷基）或--OSO2（C4-C6烷基）；n为2或3；R3为1-哌啶基、1-吡咯基、甲基-1-吡咯基、二甲基-1-吡咯基、4-吗啉基、二甲基氨基、二乙基氨基或1-己亚甲基；或其药学上可接受的盐；同时投与有效量的第二组分，该组分是式II的化合物： 其中，R4为H或较低的烷基基团，R5为较低的烷基基团，或R4和R5与相邻的氮原子结合形成杂环基团；R6为H或较低的烷基基团；R7为H、卤、OH、较低的烷基基团，或与相邻的苯环形成萘基团的丁二烯基团；R8为H或OH；n为2；或其药学上可接受的盐。
• 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：——