6-甲氧基-2-(4-甲基苯基)-1-苯并噻吩 | 185414-69-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 中文名称: 6-甲氧基-2-(4-甲基苯基)-1-苯并噻吩
• 英文名称: 6-methoxy-2-(p-tolyl)benzo[b]thiophene
• 英文别名: 6-Methoxy-2-(4-methylphenyl)-1-benzothiophene
• CAS: 185414-69-1
• 化学式: C₁₆H₁₄OS
• 分子量: 254.353
• InChiKey: KSEFJIFPJSFBSK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  37.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-甲氧基-2-(4-甲基苯基)-1-苯并噻吩 在 三氯化铝 、 丙烷-1-硫醇 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 53.0h， 生成 (6-Hydroxy-2-p-tolyl-benzo[b]thiophen-3-yl)-[4-(2-piperidin-1-yl-ethoxy)-phenyl]-methanone
  参考文献：
  名称：

  Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene

  摘要：

  The 8-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in, vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.

  DOI：

  10.1021/jm9606352
• 作为产物：
  描述：

  6-甲氧基苯并噻吩 在 四(三苯基膦)钯 、 正丁基锂 、 sodium carbonate 作用下， 生成 6-甲氧基-2-(4-甲基苯基)-1-苯并噻吩
  参考文献：
  名称：

  Toward Selective ERβ Agonists for Central Nervous System Disorders:  Synthesis and Characterization of Aryl Benzthiophenes

  摘要：

  In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ER in the brain, these compounds could lead to drugs able to separate the beneficial effects of estrogens on mood, learning, and memory from side effects such as the stimulation of endometrial and breast cancer.

  DOI：

  10.1021/jm015577l

文献信息

• Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzo[b]thiophene derivatives as potent apoptosis-inducing agents
  作者：Romeo Romagnoli、Delia Preti、Ernest Hamel、Roberta Bortolozzi、Giampietro Viola、Andrea Brancale、Salvatore Ferla、Giampaolo Morciano、Paolo Pinton

  DOI：10.1016/j.bioorg.2021.104919

  日期：2021.7

  agents, giving access to a wide range of substitution patterns at the 2-position of the 6-methoxybenzo[b]thiophene common intermediate. In the present study, all the synthesized compounds retained the 3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophene moiety, and the structure–activity relationship was examined by modification of the aryl group at its 2-position with electron-withdrawing (F) or electron-releasing

  许多临床上在癌症化疗中使用的活性剂通过靶向微管、改变蛋白质功能或抑制 DNA 合成诱导细胞死亡（细胞凋亡）发挥其活性。苯并[ b ] 噻吩支架作为抗癌药物开发的药效基团具有举足轻重的地位，此外，该支架还具有许多药理活性。我们开发了一种灵活的方法来构建新系列的 2-芳基-3-(3,4,5-三甲氧基苯胺基)-6-甲氧基苯并[ b ]噻吩作为有效的抗增殖剂，从而获得广泛的取代6-甲氧基苯并[ b] 2-位的模式]噻吩常用中间体。在本研究中，所有合成的化合物都保留了 3-(3,4,5-三甲氧基苯胺基)-6-甲氧基苯并[ b ]噻吩部分，并通过修饰芳基在其 2-位置与吸电子 (F) 或电子释放 (烷基和烷氧基) 基团。我们发现小的取代基，例如氟或甲基，可以放置在2-苯基环的对位，并且这些修饰相对于未取代的 2-苯基类似物仅略微降低抗增殖活性。化合物3a和3b，在6-甲氧基苯并[ b]的2-位带有苯基
• Toward Selective ERβ Agonists for Central Nervous System Disorders:  Synthesis and Characterization of Aryl Benzthiophenes
  作者：Ulrich Schopfer、Philippe Schoeffter、Serge F. Bischoff、Joachim Nozulak、Dominik Feuerbach、Philipp Floersheim

  DOI：10.1021/jm015577l

  日期：2002.3.1

  In an effort to identify selective ligands for the estrogen receptor subtype ERbeta, a series of aryl benzthiophenes was synthesized. In a radioligand binding assay and reporter gene assays in HeLa and SH-SY5Y cells, compounds were characterized as ERbeta-selective agonists. By targeting ER in the brain, these compounds could lead to drugs able to separate the beneficial effects of estrogens on mood, learning, and memory from side effects such as the stimulation of endometrial and breast cancer.
• Structure−Activity Relationships of Selective Estrogen Receptor Modulators:  Modifications to the 2-Arylbenzothiophene Core of Raloxifene
  作者：Timothy A. Grese、Stephen Cho、Don R. Finley、Alexander G. Godfrey、Charles D. Jones、Charles W. Lugar、Michael J. Martin、Ken Matsumoto、Lewis D. Pennington、Mark A. Winter、M. Dee Adrian、Harlan W. Cole、David E. Magee、D. Lynn Phillips、Ellen R. Rowley、Lorri L. Short、Andrew L. Glasebrook、Henry U. Bryant

  DOI：10.1021/jm9606352

  日期：1997.1.1

  The 8-arylbenzothiophene raloxifene, 1, is a selective estrogen receptor modulator which is currently under clinical evaluation for the prevention and treatment of postmenopausal osteoporosis. A series of raloxifene analogs which contain modifications to the 2-arylbenzothiophene core have been prepared and evaluated for the ability to bind to the estrogen receptor and inhibit MCF-7 breast cancer cell proliferation in vitro. Their ability to function as tissue-selective estrogen agonists in vivo has been assayed in a short-term, ovariectomized (OVX) rat model with end points of serum cholesterol lowering, uterine weight gain, and uterine eosinophil peroxidase activity. These studies have demonstrated that (1) the 6-hydroxy and, to a lesser extent, the 4'-hydroxy substituents of raloxifene are important for receptor binding and in vitro activity, (2) small, highly electronegative 4'-substituents such as hydroxy, fluoro, and chloro are preferred both in vitro and in vivo, (3) increased steric bulk at the 4'-position leads to increased uterine stimulation in, vivo, and (4) additional substitution of the 2-aryl moiety is tolerated while additional substitution at the 4-, 5-, or 7-position of the benzothiophene results in reduced biological activity. In addition, compounds in which the 2-aryl group is replaced by alkyl, cycloalkyl, and naphthyl substituents maintain a profile of in vitro and in vivo biological activity qualitatively similar to that of raloxifene. Several novel structural variants including 2-cyclohexyl, 2-naphthyl, and 6-carbomethoxy analogs also demonstrated efficacy in preventing bone loss in a chronic OVX rat model of postmenopausal osteopenia, at doses of 0.1-10 mg/kg.