1-(2,6-二氯苄基)-3-吡咯烷-1-甲基-1H-吲唑-6-胺 | 315203-39-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 中文名称: 1-(2,6-二氯苄基)-3-吡咯烷-1-甲基-1H-吲唑-6-胺
• 中文别名: 1-(2,6-二氯-苄基)-3-吡咯烷-1-基-1H-吲哚-6-胺
• 英文名称: 1-(2,6-dichlorobenzyl)-3-(pyrrolidin-1-ylmethyl)-1H-indazole-6-amine
• 英文别名: 1-(2,6-dichlorobenzyl)-3-(pyrrolidin-1-ylmethyl)-1H-indazol-6-amine；1-[(2,6-dichlorophenyl)methyl]-3-(pyrrolidin-1-ylmethyl)indazol-6-amine
• CAS: 315203-39-5
• 化学式: C₁₉H₂₀Cl₂N₄
• 分子量: 375.301
• InChiKey: RPIVQHHCHQAMGO-UHFFFAOYSA-N

物化性质

• 沸点：
  555.1±50.0 °C(Predicted)
• 密度：
  1.41±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  47.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  1-(2,6-二氯苄基)-3-吡咯烷-1-甲基-1H-吲唑-6-胺 在 盐酸 、 methyloxirane 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.25h， 生成 N_α-[(2S)-1-(3-(1-(2,6-dichlorobenzyl)-3-(pyrrolidin-1-ylmethyl)-1H-indazol-6-yl)ureido)-3-phenylpropan-2-yl]lysine benzyl amide trihydrochloride
  参考文献：
  名称：

  设计，合成和生物学评估新型基于肽的脲和硫脲作为凝血酶受体PAR1的潜在拮抗剂

  摘要：

  通过应用面向多样性的合成策略寻找凝血酶受体PAR1的新拮抗剂，已设计并合成了一系列基于肽的脲和硫脲，包括PAR1参考拮抗剂RWJ-58259的类似物。一般的合成方案包括在阮内镍的存在下通过从肼一水合物中转移氢来还原碱性氨基酸衍生的氨基腈，然后与各种异氰酸酯和异硫氰酸酯反应，并除去保护基。所有新化合物均已被评估为由PAR1激动剂SFLLRN诱导的人血小板聚集抑制剂。一些受保护的基于肽的脲显示出显着的拮抗剂活性。

  DOI：

  10.1016/j.ejmech.2012.10.015
• 作为产物：
  描述：

  1-(2,6-dichlorobenzyl)-6-nitro-3-(pyrrolidin-1-ylmethyl)-1H-indazole 在 三氯化铁 、 甲烷 、 偏二甲肼 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以1.75 g的产率得到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

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.
• Design, synthesis and biological evaluation of new peptide-based ureas and thioureas as potential antagonists of the thrombin receptor PAR1
  作者：Pilar Ventosa-Andrés、Ángel M. Valdivielso、Ioannis Pappos、M. Teresa García-López、Nikos E. Tsopanoglou、Rosario Herranz

  DOI：10.1016/j.ejmech.2012.10.015

  日期：2012.12

  By applying a diversity oriented synthesis strategy for the search of new antagonists of the thrombin receptor PAR1, a series of peptide-based ureas and thioureas, including analogues of the PAR1 reference antagonist RWJ-58259, has been designed and synthesized. The general synthetic scheme involves reduction of basic amino acid-derived amino nitriles by hydrogen transfer from hydrazine monohydrate

  通过应用面向多样性的合成策略寻找凝血酶受体PAR1的新拮抗剂，已设计并合成了一系列基于肽的脲和硫脲，包括PAR1参考拮抗剂RWJ-58259的类似物。一般的合成方案包括在阮内镍的存在下通过从肼一水合物中转移氢来还原碱性氨基酸衍生的氨基腈，然后与各种异氰酸酯和异硫氰酸酯反应，并除去保护基。所有新化合物均已被评估为由PAR1激动剂SFLLRN诱导的人血小板聚集抑制剂。一些受保护的基于肽的脲显示出显着的拮抗剂活性。