5-(4-fluorophenyl)-2,3-dihydroinden-1-one | 289056-04-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-(4-fluorophenyl)-2,3-dihydroinden-1-one
• 英文别名: 5-(4-fluorophenyl)-1-indanone
• CAS: 289056-04-8
• 化学式: C₁₅H₁₁FO
• 分子量: 226.25
• InChiKey: WMOPMYZDBMASCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-fluorophenyl)-2,3-dihydroinden-1-one 在 sodium tetrahydroborate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 169.0h， 生成 4-[5-(4-fluorophenyl)-2,3-dihydro-1H-inden-1-yl]-1,2,4-triazole
  参考文献：
  名称：

  新型咪唑基和三唑基取代的联苯化合物：合成和评估为人类17α-羟化酶-C17，20-裂解酶（P450 17）的非甾体抑制剂。

  摘要：

  描述了一系列新的P450 17抑制剂的合成。咪唑-1-基化合物5对P450 17大鼠尤其是人的酶显示出强烈的抑制作用，活性最高的化合物是5ax，5ay和5bx，IC50值分别为0.17、0.24和0.25 microM（酮康唑：0.74 microM）。1,2,4-三唑-1-基化合物6的活性较低，而1,2,4-三唑-4-基化合物7的活性较低。标题化合物显示对P450 arom几乎没有抑制作用。活性最强的P450 17抑制剂5ax和5ay在施用0.019 mmol / kg后2 h显着降低SD大鼠睾丸激素的血浆浓度。6小时后，5ay仍然表现出很强的作用。

  DOI：

  10.1016/s0968-0896(00)00076-6
• 作为产物：
  描述：

  5-溴茚酮 、 4-氟苯硼酸 在 四(三苯基膦)钯 、 cesium fluoride 作用下， 以 乙二醇二甲醚 为溶剂， 以80%的产率得到5-(4-fluorophenyl)-2,3-dihydroinden-1-one
  参考文献：
  名称：

  新型咪唑基和三唑基取代的联苯化合物：合成和评估为人类17α-羟化酶-C17，20-裂解酶（P450 17）的非甾体抑制剂。

  摘要：

  描述了一系列新的P450 17抑制剂的合成。咪唑-1-基化合物5对P450 17大鼠尤其是人的酶显示出强烈的抑制作用，活性最高的化合物是5ax，5ay和5bx，IC50值分别为0.17、0.24和0.25 microM（酮康唑：0.74 microM）。1,2,4-三唑-1-基化合物6的活性较低，而1,2,4-三唑-4-基化合物7的活性较低。标题化合物显示对P450 arom几乎没有抑制作用。活性最强的P450 17抑制剂5ax和5ay在施用0.019 mmol / kg后2 h显着降低SD大鼠睾丸激素的血浆浓度。6小时后，5ay仍然表现出很强的作用。

  DOI：

  10.1016/s0968-0896(00)00076-6

文献信息

• Receptor Function Regulator
  申请人：Fukatsu Kohji

  公开号：US20090012093A1

  公开（公告）日：2009-01-08

  The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明的GPR40受体功能调节剂包括具有芳香环和能够释放阳离子的基团的化合物，可用作胰岛素分泌剂或预防或治疗糖尿病等疾病的药剂。
• GPR40 Receptor function regulator
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP2385032A1

  公开（公告）日：2011-11-09

  The GPR40 receptor function regulator of the present invention, which comprises a compound having an aromatic ring and a group capable of releasing cation is useful as an insulin secretagogue or an agent for the prophylaxis or treatment of diabetes and the like.

  本发明的 GPR40 受体功能调节剂由具有芳香环和能够释放阳离子的基团的化合物组成，可用作胰岛素分泌剂或预防或治疗糖尿病等的药物。
• RECEPTOR FUNCTION CONTROLLING AGENT
  申请人：Takeda Pharmaceutical Company Limited

  公开号：EP1559422B1

  公开（公告）日：2014-04-30
• 6-Aryl-8<i>H</i>-indeno[1,2-<i>d</i>]thiazol-2-ylamines:  A₁ Adenosine Receptor Agonist Allosteric Enhancers Having Improved Potency
  作者：Mahendra D. Chordia、Molly Zigler、Lauren J. Murphree、Heidi Figler、Timothy L. Macdonald、Ray A. Olsson、Joel Linden

  DOI：10.1021/jm049132j

  日期：2005.8.1

  Allosteric enhancers (AEs) of the A(1) adenosine receptor (A(1)AR) have potential as drugs for treating neurological, cardiovascular, and renal diseases. This report describes the synthesis and evaluation of a series of 6-aryl-8H-indeno[1,2-d]thiazol-2-ylamines that exhibited AE activity at the A(1)AR. Palladium-mediated condensation of arylboronic acids with 5-bromoindan-1-one generated arylindanones 2a-aj for iodine-catalyzed condensation with thiourea, generating 2-aminothiazolium salts 3a-aj. Binding studies using membranes from cells stably expressing human A(1)ARs, A(2A)ARs, or A(3)ARs evaluated AE activity and receptor subtype selectivity. The EC50 of the AE activities of compounds 3m-o, 3x, and 3ae were 2.2, 1.5, 0.9, 1.0, and 3.0,mu M, respectively, substantially lower than that of the well characterized 2-amino3-aroylthiophene (PD 81,723), > 10 mu M. The new compounds also have substantially higher maximal AE activity. These compounds had no AE activity at the A(2A)AR and only minimal activity at the A(3)AR.
• Synthesis, Biological Evaluation, and Molecular Modeling of Abiraterone Analogues: Novel CYP17 Inhibitors for the Treatment of Prostate Cancer
  作者：Mariano A. E. Pinto-Bazurco Mendieta、Matthias Negri、Carsten Jagusch、Ursula Müller-Vieira、Thomas Lauterbach、Rolf W. Hartmann

  DOI：10.1021/jm800355c

  日期：2008.8.1

  Abiraterone, a steroidal cytochrome P450 17alpha-hydroxylase-17,20-lyase inhibitor (CYP17), is currently undergoing phase II clinical trials as a potential drug for the treatment of androgen-dependent prostate cancer. Since steroidal compounds often show side effects attributable to their structure, we have tried to replace the sterane scaffold by nonsteroidal core structures. The design and synthesis of 20 new abiraterone mimetics are described. Their activities have been tested with recombinant human CYP17 expressed in E. coli. Promising compounds were further evaluated for selectivity against CYP11B1, CYP11B2, and the hepatic CYP3A4. Compounds 19 and 20 showed comparable activity to abiraterone (IC50 values of 144 and 64 nM vs 72 nM) and similar or even better selectivity against the other CYP enzymes. Selected compounds were also docked into our homology model, and the same binding modes as for abiraterone were found.