6-methoxy-5-{[2-(trimethylsilyl)ethoxy]methoxy}indan-1-one | 760991-74-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 6-methoxy-5-{[2-(trimethylsilyl)ethoxy]methoxy}indan-1-one
• 英文别名: 6-methoxy-5-(2-trimethylsilylethoxymethoxy)-2,3-dihydroinden-1-one
• CAS: 760991-74-0
• 化学式: C₁₆H₂₄O₄Si
• 分子量: 308.45
• InChiKey: FTMFHKMVPIFNGG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-methoxy-5-{[2-(trimethylsilyl)ethoxy]methoxy}indan-1-one 、 phenyl 6-chloronicotinate 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 生成
  参考文献：
  名称：

  Cyanopyridyl containing 1,4-dihydroindeno[1,2-c]pyrazoles as potent checkpoint kinase 1 inhibitors: Improving oral biovailability

  摘要：

  A series of 1,4-dihydroindeno[1,2-c]pyrazole compounds with a cyanopyridine moiety at the 3-position of the tricyclic pyrazole core was explored as potent CHK-1 inhibitors. The impact of substitutions at the 6 and/or 7-position of the core on pharmacokinetic properties was studied in detail. Compounds carrying a side chain with an ether linker at the 7-position and a terminal morpholino group, such as 29 and 30, exhibited much-improved oral biovailability in mice as compared to earlier generation inhibitors. These compounds also possessed desirable cellular activity in potentiating doxorubicin and will serve as valuable tool compounds for in vivo evaluation of CHK-1 inhibitors to sensitize DNA-damaging agents. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.069
• 作为产物：
  描述：

  5-羟基-6-甲氧基-1-茚满酮 、 2-(三甲基硅烷基)乙氧甲基氯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以72%的产率得到6-methoxy-5-{[2-(trimethylsilyl)ethoxy]methoxy}indan-1-one
  参考文献：
  名称：

  [EN] FUSED TRI AND TETRA-CYCLIC PYRAZOLE KINASE INHIBITORS
  [FR] INHIBITEURS DE PYRAZOLE KINASE FUSIONNEE TRICYCLIQUE ET TETRACYCLIQUE

  摘要：

  具有化学式(I) (I)的化合物对抑制蛋白激酶很有用。还公开了制备这些化合物的方法、含有这些化合物的组合物，以及使用这些化合物进行治疗的方法。

  公开号：

  WO2004080973A1

文献信息

• Fused tri and tetra-cyclic pyrazole kinase inhibitors
  申请人：——

  公开号：US20040259904A1

  公开（公告）日：2004-12-23

  Compounds having the formula (I) 1 are useful for inhibiting protein kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  化合物具有公式（I）1，对于抑制蛋白激酶具有用途。还公开了制备该化合物的方法，含有该化合物的组合物以及使用该化合物的治疗方法。
• Discovery of 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles and 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-pyridine-2′-carbonitriles as potent checkpoint kinase 1 (Chk1) inhibitors
  作者：Zhi-Fu Tao、Gaoquan Li、Yunsong Tong、Kent D. Stewart、Zehan Chen、Mai-Ha Bui、Philip Merta、Chang Park、Peter Kovar、Haiying Zhang、Hing L. Sham、Saul H. Rosenberg、Thomas J. Sowin、Nan-Horng Lin

  DOI：10.1016/j.bmcl.2007.07.102

  日期：2007.11

  An extensive structure-activity relationship study of the 3-position of a series of tricyclic pyrazole-based Chk1 inhibitors is described. As a result, 4'-,1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles (4) and 4'-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)pyridine-2'-carbonitriles (29) emerged as new lead series. Compared with the original lead compound 2, these new leads fully retain the biological activity in both enzymatic inhibition and cell-based assays. More importantly, the new leads 4 and 29 exhibit favorable physicochemical properties such as lower molecular weight, lower Clog P, and the absence of a hydroxyl group. Furthermore, structure-activity relationship studies were performed at the 6- and 7-positions of 4, which led to the identification of ideal Chk1 inhibitors 49, 50, 51, and 55. These compounds not only potently inhibit Chk1 in an enzymatic assay but also significantly potentiate the cytotoxicity of DNA-damaging agents in cell-based assays while they show little single agent activity. A cell cycle analysis by FACS confirmed that these Chk1 inhibitors efficiently abrogate the G2/M and S checkpoints induced by DNA-damaging agent. The current work paved the way to the identification of several potent Chk1 inhibitors with good pharmacokinetics that are suitable for in vivo study with oral dosing. (c) 2007 Elsevier Ltd. All rights reserved.