3-iodo-1,4-dihydroindeno[1,2-c]pyrazole-6-carbaldehyde | 760989-13-7

• 分子结构分类: 有机化合物 - 苯类化合物
• 英文名称: 3-iodo-1,4-dihydroindeno[1,2-c]pyrazole-6-carbaldehyde
• 英文别名: 3-iodo-2,4-dihydroindeno[1,2-c]pyrazole-6-carbaldehyde
• CAS: 760989-13-7
• 化学式: C₁₁H₇IN₂O
• 分子量: 310.094
• InChiKey: XMSQOPFJOHCUMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  45.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-iodo-1,4-dihydroindeno[1,2-c]pyrazole-6-carbaldehyde 在 bis-triphenylphosphine-palladium(II) chloride sodium tetrahydroborate 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 生成 4'-[6-(hydroxymethyl)-1,4-dihydroindeno[1,2-c]pyrazol-3-yl]-1,1'-biphenyl-4-ol
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles as potent checkpoint kinase 1 inhibitors: Extended exploration on phenyl ring substitutions and preliminary ADME/PK studies

  摘要：

  A study on substitutions at the four open positions on the phenyl ring of the 1,4-dihydroindeno[1,2-c]pyrazoles as potent CHK-1 inhibitors is described. Bis-substitution at both the 6- and 7-positions led to inhibitors with IC50 values below 0.3 nM. The compound with the best overall activities (36) was able to potentiate the anti-proliferative effect of doxorubicin in HeLa cells by at least 47-fold. Physicochemical, metabolic, and pharmacokinetic properties of selected inhibitors are also disclosed. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.04.055
• 作为产物：
  描述：

  1,4-dihydroindeno[1,2-c]pyrazole-6-carbaldehyde 在 N-碘代丁二酰亚胺 作用下， 以 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 5.5h， 以64%的产率得到3-iodo-1,4-dihydroindeno[1,2-c]pyrazole-6-carbaldehyde
  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。
• Tricyclic pyrazole kinase inhibitors
  申请人：Arnold D. Lee

  公开号：US20060014816A1

  公开（公告）日：2006-01-19

  Compounds of the present invention are useful for inhibiting protein tyrosine kinases. Also disclosed are methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

  本发明的化合物可用于抑制蛋白酪氨酸激酶。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 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of potent and selective checkpoint kinase 1 inhibitors
  作者：Yunsong Tong、Akiyo Claiborne、Kent D. Stewart、Chang Park、Peter Kovar、Zehan Chen、Robert B. Credo、Wen-Zhen Gu、Stephen L. Gwaltney、Russell A. Judge、Haiying Zhang、Saul H. Rosenberg、Hing L. Sham、Thomas J. Sowin、Nan-horng Lin

  DOI：10.1016/j.bmc.2007.01.012

  日期：2007.4

  A new class of checkpoint kinase 1 (CHK-1) inhibitors bearing a 1,4-dihydroindeno[1,2-c]pyrazole core was developed after initial hits from high throughput screening. The efficient hit-to-lead process was facilitated by X-ray crystallography and led to potent inhibitors (< 10 nM) against CHK-1. X-ray co-crystal structures of bound inhibitors demonstrated that two sub-series of this class of compounds, exemplified by 21 and 41, exhibit distinctive hydrogen bonding patterns in the specificity pocket of the active site. Two compounds, 41 and 43, were capable of potentiating doxorubicin and camptothecin, both DNA-damaging agents, in cell proliferation assays (MTS and soft agar assays) and abrogating G2/M checkpoint in a mechanism-based FACS assay. (c) 2007 Elsevier Ltd. All rights reserved.
• 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
• TRICYCLIC PYRAZOLE KINASE INHIBITORS
  申请人：AbbVie Inc.

  公开号：EP1740579B1

  公开（公告）日：2015-08-19