(1-oxo-2,3-dihydro-1H-inden-5-yl)methyl methanesulfonate | 760995-54-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (1-oxo-2,3-dihydro-1H-inden-5-yl)methyl methanesulfonate
• 英文别名: (1-oxo-2,3-dihydroinden-5-yl)methyl methanesulfonate
• CAS: 760995-54-8
• 化学式: C₁₁H₁₂O₄S
• 分子量: 240.28
• InChiKey: UIZQLMOWEQCIML-UHFFFAOYSA-N

物化性质

• 沸点：
  464.7±34.0 °C(Predicted)
• 密度：
  1.371±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  68.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1-oxo-2,3-dihydro-1H-inden-5-yl)methyl methanesulfonate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide sodium hydride 、 potassium carbonate 、 一水合肼 、 溶剂黄146 、 三乙胺 、 三苯基膦 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 苯 为溶剂， 反应 6.5h， 生成 ethyl 2-(3-(4-(6-((4-methylpiperazin-1-yl)methyl)-1,4-dihydroindeno[1,2-c]pyrazol-3-yl)thiophen-2-yl)prop-2-ynyloxy)acetate
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o
• 作为产物：
  描述：

  2,3-dihydrospiro[indene-1,2'-[1,3]dioxolane]-5-carbaldehyde 在 sodium tetrahydroborate 、 对甲苯磺酸 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 水 、 丙酮 为溶剂， 生成 (1-oxo-2,3-dihydro-1H-inden-5-yl)methyl methanesulfonate
  参考文献：
  名称：

  1,4-Dihydroindeno[1,2-c]pyrazoles with Acetylenic Side Chains as Novel and Potent Multitargeted Receptor Tyrosine Kinase Inhibitors with Low Affinity for the hERG Ion Channel

  摘要：

  The synthesis of a novel series of 1,4-dihydroindeno[1,2-c]pyrazoles with acetylene-type side chains is described. Optimization of those compounds as KDR kinase inhibitors identified 8, which displayed an oral activity in an estradiol-induced murine uterine edema model (ED50 = 3 mg/kg) superior to Sutent (ED50 = 9 mg/kg) and showed potent antitumor efficacy in an MX-1 human breast carcinoma xenograft tumor growth model (tumor growth inhibition = 90% at 25 mg/kg.day po). The compound was docked into a homology model of the homo-tetrameric pore domain of the hERG potassium channel to identify strategies to improve its cardiac safety profile. Systematic interruption of key binding interactions between 8 and Phe656, Tyr652, and Ser624 yielded 90, which only showed an IC50 of 11.6 mu M in the hERG patch clamp assay. The selectivity profile for 8 and 90 revealed that both compounds are multitargeted receptor tyrosine kinase inhibitors with low nanomolar potencies against the members of the VEGFR and PDGFR kinase subfamilies.

  DOI：

  10.1021/jm061223o

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。
• 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。
• Hit-to-lead optimization of 1,4-dihydroindeno[1,2-c]pyrazoles as a novel class of KDR kinase inhibitors
  作者：Jürgen Dinges、Irini Akritopoulou-Zanze、Lee D. Arnold、Teresa Barlozzari、Peter F. Bousquet、George A. Cunha、Anna M. Ericsson、Nobuhiko Iwasaki、Michael R. Michaelides、Nobuo Ogawa、Kathleen M. Phelan、Paul Rafferty、Thomas J. Sowin、Kent D. Stewart、Ryukou Tokuyama、Zhiren Xia、Henry Q. Zhang

  DOI：10.1016/j.bmcl.2006.05.052

  日期：2006.8

  A series of 1,4-dihydroindeno[1,2-c]pyrazoles was prepared and evaluated for their enzymatic inhibition of KDR kinase. Computer modeling studies revealed the importance of attaching a basic side chain in predicting The binding mode of those compounds. Further investigation of structure-activity relationships led to 19, a lead compound with an acceptable selectivity profile, activity in whole cells, and good oral efficacy in an estradiol-induced murine uterine edema model of VEGF activity. (c) 2006 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