5-(benzyloxy)-2-(4-bromobenzoyl)-6-methoxyindan-1-one | 760992-27-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-(benzyloxy)-2-(4-bromobenzoyl)-6-methoxyindan-1-one
• 英文别名: 2-(4-Bromobenzoyl)-6-methoxy-5-phenylmethoxy-2,3-dihydroinden-1-one
• CAS: 760992-27-6
• 化学式: C₂₄H₁₉BrO₄
• 分子量: 451.316
• InChiKey: RPZKJNNNRLOVRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(benzyloxy)-2-(4-bromobenzoyl)-6-methoxyindan-1-one 在 溶剂黄146 、 肼 作用下， 以 乙醇 为溶剂， 生成 4'-{6-[3-(dimethylamino)propoxy]-7-methoxy-1,4-dihydroindeno[1,2-c]pyrazol-3-yl}-1,1'-biphenyl-4-ol
  参考文献：
  名称：

  Synthesis and biological evaluation of 4′-(6,7-disubstituted-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-biphenyl-4-ol as potent Chk1 inhibitors

  摘要：

  A new series of potent tricyclic pyrazole-based Chk1 inhibitors are described. Analogues disubstituted on the 6- and 7positions show improved Chk1 inhibition potency compared with analogues with a single substituent on either the 6- or 7-position. Based on the lead compound 4'-(6,7-dimethoxy-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-bipheny1-4-ol (2), detailed SAR studies on the 6- and 7-positions were performed. 3'-morpholin-4'-yl-propoxy, pyridin-4'-ylmethoxy, pyridin-3'-ylmethoxy, 2'-(5"-ethyl-pyridin-2"-yl)-ethoxy, pyridin-2'-ylethoxy, (6'-methyl-pyridin-2'-yl)-propoxyethoxy, 2',3'-dihydroxyl-l'-yl-propoxy, and tetrahydro-furan-3'-yloxy have been identified as the best groups on the 6-position when the 7-position is substituted with methoxyl group. Pyridin-2'-ylmethoxy and pyridin-3'-ylmethoxy have been identified as the best substituents at the 7-position while the 6-position bearing methoxyl group. These compounds significantly potentiate the cytotoxicity of DNA-damaging antitumor agents in a cell-based assay and efficiently abrogate the doxorubicin-induced G2/M and the camptothecin-induced S checkpoints, suggesting that their potent biological activities are mechanism-based through Chk1 inhibition. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.027
• 作为产物：
  描述：

  4-溴苯甲酸 在 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-(benzyloxy)-2-(4-bromobenzoyl)-6-methoxyindan-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of 4′-(6,7-disubstituted-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-biphenyl-4-ol as potent Chk1 inhibitors

  摘要：

  A new series of potent tricyclic pyrazole-based Chk1 inhibitors are described. Analogues disubstituted on the 6- and 7positions show improved Chk1 inhibition potency compared with analogues with a single substituent on either the 6- or 7-position. Based on the lead compound 4'-(6,7-dimethoxy-2,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-bipheny1-4-ol (2), detailed SAR studies on the 6- and 7-positions were performed. 3'-morpholin-4'-yl-propoxy, pyridin-4'-ylmethoxy, pyridin-3'-ylmethoxy, 2'-(5"-ethyl-pyridin-2"-yl)-ethoxy, pyridin-2'-ylethoxy, (6'-methyl-pyridin-2'-yl)-propoxyethoxy, 2',3'-dihydroxyl-l'-yl-propoxy, and tetrahydro-furan-3'-yloxy have been identified as the best groups on the 6-position when the 7-position is substituted with methoxyl group. Pyridin-2'-ylmethoxy and pyridin-3'-ylmethoxy have been identified as the best substituents at the 7-position while the 6-position bearing methoxyl group. These compounds significantly potentiate the cytotoxicity of DNA-damaging antitumor agents in a cell-based assay and efficiently abrogate the doxorubicin-induced G2/M and the camptothecin-induced S checkpoints, suggesting that their potent biological activities are mechanism-based through Chk1 inhibition. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.027

文献信息

• [EN] FUSED TRI AND TETRA-CYCLIC PYRAZOLE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE PYRAZOLE KINASE FUSIONNEE TRICYCLIQUE ET TETRACYCLIQUE
  申请人：ABBOTT LAB

  公开号：WO2004080973A1

  公开（公告）日：2004-09-23

  Compounds having the formula (I) (I), 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.

  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。
• 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。
• FUSED TRI AND TETRA-CYCLIC PYRAZOLE KINASE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP1603885A1

  公开（公告）日：2005-12-14
• US7320986B2
  申请人：——

  公开号：US7320986B2

  公开（公告）日：2008-01-22