tert-butyl 4-(3-azido-2-nitrophenyl)piperazine-1-carboxylate | 1046790-51-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(3-azido-2-nitrophenyl)piperazine-1-carboxylate
• CAS: 1046790-51-5
• 化学式: C₁₅H₂₀N₆O₄
• 分子量: 348.362
• InChiKey: XUYIHBQKVOXWSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  93
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-azido-2-nitrophenyl)piperazine-1-carboxylate 在 tin(ll) chloride 作用下， 以 甲醇 为溶剂， 以226 mg的产率得到4-(3-氨基-2-硝基苯基)哌嗪-1-羧酸叔丁酯
  参考文献：
  名称：

  2-Phenyl-4-piperazinylbenzimidazoles: Orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor

  摘要：

  Antagonism of the gonadotropin releasing hormone (GnRH) receptor has shown positive clinical results in numerous reproductive tissue disorders such as endometriosis, prostate cancer and others. Traditional therapy has been limited to peptide agonists and antagonists. Recently, small molecule GnRH antagonists have emerged as potentially new treatments. This article describes the discovery of 2-phenyl-4-piperazinylbenzimidazoles as small molecule GnRH antagonists with nanomolar potency in in vitro binding and functional assays, excellent bioavailability (rat % F > 70) and demonstrated oral activity in a rat model having shown significant serum leuteinizing hormone (LH) suppression. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.024
• 作为产物：
  描述：

  2,6-二氟硝基苯 在 sodium azide 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 49.0h， 生成 tert-butyl 4-(3-azido-2-nitrophenyl)piperazine-1-carboxylate
  参考文献：
  名称：

  促性腺激素释放激素（GnRH）受体的小分子哌嗪基-苯并咪唑拮抗剂

  摘要：

  在此交流中，我们报告了基于铜催化的叠氮化物炔烃环加成反应的基于2-（4-叔丁基苯基）-4-哌嗪基-苯并咪唑骨架的人类促性腺激素释放激素受体小分子拮抗剂库的合成和表征。我们的主要目的是找到一种基于WAY207024的可溶性更强的化合物，具有纳摩尔浓度的抑制GnRH受体的能力。此外，还开发了通过使用点击化学技术来实现后期多样化的方法，以允许在将来的优化中扩展库。在功能测定中测试了所有化合物，以确定内源激动剂GnRH抑制受体刺激的个体效力。总之，我们发现与WAY207024相比，化合物8a的溶解度有所改善，并且与GnRH受体的纳摩尔亲和力更高。

  DOI：

  10.1039/c7md00320j

文献信息

• 1-(ARYLSULFONYL)-4-(PIPERAZIN-1-YL)-1H-BENZIMIDAZOLES AS 5-HYDROXYTRYPTAMINE-6 LIGANDS
  申请人：Haydar Simon Nicolas

  公开号：US20100120779A1

  公开（公告）日：2010-05-13

  The invention relates to 1-(arylsulfonyl)-4-(piperazin-1-yl)-1H-benzimidazole compounds of the Formula I: or a tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.

  该发明涉及Formula I的1-(芳基磺酰基)-4-(哌嗪-1-基)-1H-苯并咪唑化合物，或其互变体、立体异构体或药用可接受盐，其中组成变量如本文所定义，包括含有这些化合物的组合物，以及制备和使用这些化合物的方法。
• 2-METHYL-1-(PHENYLSULFONYL)-4-(PIPERAZIN-1-YL)-1H-BENZIMIDAZOLE AS 5-HYDROXYTRYPTAMINE-6 LIGAND
  申请人：Wyeth LLC

  公开号：EP2285784B1

  公开（公告）日：2012-07-04
• US8063053B2
  申请人：——

  公开号：US8063053B2

  公开（公告）日：2011-11-22
• [EN] 1- (ARYLSULFONYL) -4- (PI PERAZIN-I -YL) -IH-BENZ IMIDAZOLES AS d-HYDROXYTRYPTAMINE- 6 LIGANDS<br/>[FR] 1-(ARYLSULFONYL)-4-(PIPÉRAZIN-1-YL)-1H-BENZIMIDAZOLES EN TANT QUE LIGANDS DE ?-HYDROXYTRIPTAMINE-6
  申请人：WYETH LLC

  公开号：WO2010056644A1

  公开（公告）日：2010-05-20

  The invention relates to 1-(arylsulfonyl)-4-(piperazin-1-yl)-1H-benzimidazole compounds of the Formula I: or a tautomer, stereoisomer, or pharmaceutically acceptable salt thereof, wherein the constituent variables are as defined herein, compositions comprising the compounds, and methods for making and using the compounds.
• 2-Phenyl-4-piperazinylbenzimidazoles: Orally active inhibitors of the gonadotropin releasing hormone (GnRH) receptor
  作者：Jeffrey C. Pelletier、Murty Chengalvala、Josh Cottom、Irene Feingold、Lloyd Garrick、Daniel Green、Diane Hauze、Christine Huselton、James Jetter、Wenling Kao

  DOI：10.1016/j.bmc.2008.05.024

  日期：2008.7.1

  Antagonism of the gonadotropin releasing hormone (GnRH) receptor has shown positive clinical results in numerous reproductive tissue disorders such as endometriosis, prostate cancer and others. Traditional therapy has been limited to peptide agonists and antagonists. Recently, small molecule GnRH antagonists have emerged as potentially new treatments. This article describes the discovery of 2-phenyl-4-piperazinylbenzimidazoles as small molecule GnRH antagonists with nanomolar potency in in vitro binding and functional assays, excellent bioavailability (rat % F > 70) and demonstrated oral activity in a rat model having shown significant serum leuteinizing hormone (LH) suppression. (c) 2008 Elsevier Ltd. All rights reserved.