6-nitro-3-(pyrrolidin-1-ylmethyl)-1H-indazole | 315203-38-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 6-nitro-3-(pyrrolidin-1-ylmethyl)-1H-indazole
• 英文别名: 1H-Indazole, 6-nitro-3-(1-pyrrolidinylmethyl)-；6-nitro-3-(pyrrolidin-1-ylmethyl)-2H-indazole
• CAS: 315203-38-4
• 化学式: C₁₂H₁₄N₄O₂
• 分子量: 246.269
• InChiKey: NRSKLXDGNBZSMP-UHFFFAOYSA-N

物化性质

• 沸点：
  441.4±30.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  77.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-nitro-3-(pyrrolidin-1-ylmethyl)-1H-indazole 在 氢氧化钾 、 三氯化铁 、 甲烷 、 偏二甲肼 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 1-(2,6-二氯苄基)-3-吡咯烷-1-甲基-1H-吲唑-6-胺
  参考文献：
  名称：

  发现和优化新型凝血酶受体（par-1）拮抗剂：基于吲哚和吲唑模板的有效选择性肽模拟物。

  摘要：

  DOI：

  10.1021/jm000506s
• 作为产物：
  描述：

  6-硝基吲哚 在 三乙酰氧基硼氢化钠 、 溶剂黄146 、 sodium nitrite 作用下， 以 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 6-nitro-3-(pyrrolidin-1-ylmethyl)-1H-indazole
  参考文献：
  名称：

  发现和优化新型凝血酶受体（par-1）拮抗剂：基于吲哚和吲唑模板的有效选择性肽模拟物。

  摘要：

  DOI：

  10.1021/jm000506s

文献信息

• Discovery and Optimization of a Novel Series of Thrombin Receptor (PAR-1) Antagonists:  Potent, Selective Peptide Mimetics Based on Indole and Indazole Templates
  作者：Han-Cheng Zhang、Claudia K. Derian、Patricia Andrade-Gordon、William J. Hoekstra、David F. McComsey、Kimberly B. White、Brenda L. Poulter、Michael F. Addo、Wai-Man Cheung、Bruce P. Damiano、Donna Oksenberg、Elwood E. Reynolds、Anjali Pandey、Robert M. Scarborough、Bruce E. Maryanoff

  DOI：10.1021/jm000506s

  日期：2001.3.1
• US7417030B2
  申请人：——

  公开号：US7417030B2

  公开（公告）日：2008-08-26
• Characterization of Protease-Activated Receptor (PAR) ligands: Parmodulins are reversible allosteric inhibitors of PAR1-driven calcium mobilization in endothelial cells
  作者：Disha M. Gandhi、Mark W. Majewski、Ricardo Rosas、Kaitlin Kentala、Trevor J. Foster、Eric Greve、Chris Dockendorff

  DOI：10.1016/j.bmc.2018.04.016

  日期：2018.5

  Several classes of ligands for Protease-Activated Receptors (PARs) have shown impressive anti-inflammatory and cytoprotective activities, including PAR2 antagonists and the PAR1-targeting parmodulins. In order to support medicinal chemistry studies with hundreds of compounds and to perform detailed mode-of-action studies, it became important to develop a reliable PAR assay that is operational with endothelial cells, which mediate the cytoprotective effects of interest. We report a detailed protocol for an intracellular calcium mobilization assay with adherent endothelial cells in multiwell plates that was used to study a number of known and new PAR1 and PAR2 ligands, including an alkynylated version of the PAR1 antagonist RWJ-58259 that is suitable for the preparation of tagged or conjugate compounds. Using the cell line EA. hy926, it was necessary to perform media exchanges with automated liquid handling equipment in order to obtain optimal and reproducible antagonist concentration-response curves. The assay is also suitable for study of PAR2 ligands; a peptide antagonist reported by Fairlie was synthesized and found to inhibit PAR2 in a manner consistent with reports using epithelial cells. The assay was used to confirm that vorapaxar acts as an irreversible antagonist of PAR1 in endothelium, and parmodulin 2 (ML161) and the related parmodulin RR-90 were found to inhibit PAR1 reversibly, in a manner consistent with negative allosteric modulation. (C) 2018 Elsevier Ltd. All rights reserved.