4-溴-1H-吲唑-6-腈 | 898746-96-8

• 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: 4-溴-1H-吲唑-6-腈
• 英文名称: 4-bromo-1H-indazole-6-carbonitrile
• CAS: 898746-96-8
• 化学式: C₈H₄BrN₃
• 分子量: 222.044
• InChiKey: MECMIAFNEMHEPY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  52.5
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 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：

  4-溴-1H-吲唑-6-腈 在 tris-(dibenzylideneacetone)dipalladium(0) 、 copper diacetate 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 吡啶 、 氢氧化钾 、 水 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 145.0h， 生成 1-{3,5-difluoro-4-[(phenylmethyl)oxy]phenyl}-4-hydroxy-1H-indazole-6-carbonitrile
  参考文献：
  名称：

  WO2008/107455

  摘要：

  公开号：

文献信息

• [EN] METTL3 INHIBITORY COMPOUNDS<br/>[FR] COMPOSÉS INHIBITEURS DE METTL3
  申请人：STORM THERAPEUTICS LTD

  公开号：WO2020201773A1

  公开（公告）日：2020-10-08

  The present invention relates to compounds of formula (I) that function as inhibitors of METTL3 (N6-adenosine-methyltransferase 70 kDa subunit) enzyme activity: X-Y-Z5 (I) wherein X, Y and Z are each as defined herein. The present invention also relates to processes for the preparation of these compounds, to pharmaceutical compositions comprising them, and to their use in the treatment of proliferative disorders, such as cancer, and autoimmune diseases, as well as other diseases or conditions in which METTL3 activity 10 is implicated.

  本发明涉及作为METTL3（N6-腺苷甲基转移酶70kDa亚基）酶活性抑制剂的化合物(I)的公式，其中X、Y和Z分别如本文所定义。本发明还涉及制备这些化合物的方法，包括含有它们的药物组合物，以及它们在治疗增殖性疾病（如癌症）和自身免疫疾病以及METTL3活性有关的其他疾病或病况中的用途。
• Unprotected Indazoles Are Resilient to Ring-Opening Isomerization: A Case Study on Catalytic C–S Couplings in the Presence of Strong Base
  作者：Jacob M. Ganley、Charles S. Yeung

  DOI：10.1021/acs.joc.7b02712

  日期：2017.12.15

  Indazoles represent a privileged scaffold in medicinal chemistry. In the presence of strong base, however, N-protected indazoles are prone to an undesirable ring-opening reaction to liberate o-aminobenzonitriles. By employing unprotected indazoles with a free N–H bond, isomerization is averted because the heterocycle is deprotonated in situ. We herein report functional group-tolerant and robust C–S

  吲唑是药物化学中的一种特殊支架。然而，在强碱的存在下，N-保护的吲唑易于发生不希望的开环反应以释放邻氨基苯甲腈。通过使用带有NH键的未保护的吲唑，由于杂环被原位去质子化，因此可以避免异构化。我们在本文中报道了在双（三甲基甲硅烷基）酰胺锂存在下，溴吲唑与具有不同电子性质的硫醇的官能团耐受性和稳健的C–S偶联。
• Indazoles Used To Treat Estrogen Receptor Beta Mediated Disorders
  申请人：Johnson Christopher Norbert

  公开号：US20100087502A1

  公开（公告）日：2010-04-08

  The present invention relates to novel indazole derivatives having pharmacological activity, processes for their preparation, compositions containing them and uses of these compounds in the treatment of estrogen receptor beta mediated diseases.

  本发明涉及具有药理活性的新型吲唑衍生物，其制备过程，包含它们的组成物和这些化合物在治疗雌激素受体β介导的疾病中的用途。
• Indazoles used to treat estrogen receptor beta mediated disorders
  申请人：Glaxo Group Limited

  公开号：US07960563B2

  公开（公告）日：2011-06-14

  The present invention relates to novel indazole derivatives having pharmacological activity, processes for their preparation, compositions containing them and uses of these compounds in the treatment of estrogen receptor beta mediated diseases.

  本发明涉及具有药理活性的新型吲唑衍生物，其制备方法、含有它们的组合物以及这些化合物在治疗雌激素受体β介导的疾病中的用途。
• Discovery of potent, reversible MetAP2 inhibitors via fragment based drug discovery and structure based drug design—Part 1
  作者：Zacharia Cheruvallath、Mingnam Tang、Christopher McBride、Mallareddy Komandla、Joanne Miura、Thu Ton-Nu、Phil Erikson、Jun Feng、Pamela Farrell、J. David Lawson、Darin Vanderpool、Yiqin Wu、Douglas R. Dougan、Artur Plonowski、Corine Holub、Chris Larson

  DOI：10.1016/j.bmcl.2016.04.073

  日期：2016.6

  Methionine aminopeptidase 2 (MetAP2) is an enzyme that cleaves an N-terminal methionine residue from a number of newly synthesized proteins. Pre-clinical and clinical studies suggest that MetAP2 inhibitors could be used as a novel treatment for obesity. Herein we describe our use of fragment screening methods and structural biology to quickly identify and elaborate an indazole fragment into a series of reversible MetAP2 inhibitors with < 10 nM potency, excellent selectivity, and favorable in vitro safety profiles. (C) 2016 Elsevier Ltd. All rights reserved.