4-chloro-2-iodo-1-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridine | 1312581-05-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 4-chloro-2-iodo-1-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridine
• 英文别名: 4-Chloro-2-iodo-1-(methoxymethyl)pyrrolo[2,3-b]pyridine
• CAS: 1312581-05-7
• 化学式: C₉H₈ClIN₂O
• 分子量: 322.533
• InChiKey: SNCUACRBMUHQER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-2-iodo-1-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridine 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 盐酸 、 N-碘代丁二酰亚胺 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 17.5h， 生成 4-[4-chloro-1-methoxymethyl-2-(4-piperazin-1-yl-phenyl)-7-azaindole]-benzoic acid ethyl ester
  参考文献：
  名称：

  [EN] AZAINDOLE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
  [FR] DÉRIVÉS D'AZAINDOLE, LEUR PRÉPARATION ET LEUR APPLICATION THÉRAPEUTIQUE

  摘要：

  该披露通常涉及抑制Pim激酶的化合物。本文提供了N-取代的氮杂吲哚，或其药用盐，这些化合物可作为Pim激酶的选择性抑制剂。该披露还涉及包含这些化合物的药物组合物，其制备方法以及使用这些化合物的方法。

  公开号：

  WO2011075613A1
• 作为产物：
  描述：

  4-氯-7-氮杂吲哚 在 四丁基硫酸氢铵 、 sodium hydroxide 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 、 乙腈 为溶剂， 反应 6.33h， 生成 4-chloro-2-iodo-1-(methoxymethyl)-1H-pyrrolo[2,3-b]pyridine
  参考文献：
  名称：

  [EN] AZAINDOLE DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION
  [FR] DÉRIVÉS D'AZAINDOLE, LEUR PRÉPARATION ET LEUR APPLICATION THÉRAPEUTIQUE

  摘要：

  该披露通常涉及抑制Pim激酶的化合物。本文提供了N-取代的氮杂吲哚，或其药用盐，这些化合物可作为Pim激酶的选择性抑制剂。该披露还涉及包含这些化合物的药物组合物，其制备方法以及使用这些化合物的方法。

  公开号：

  WO2011075613A1

文献信息

• Discovery of N -substituted 7-azaindoles as PIM1 kinase inhibitors – Part I
  作者：Claude Barberis、Neil Moorcroft、Chris Arendt、Mikhail Levit、Sandra Moreno-Mazza、Joseph Batchelor、Ingrid Mechin、Tahir Majid

  DOI：10.1016/j.bmcl.2017.08.069

  日期：2017.10

  Novel N-substituted azaindoles have been discovered as PIM1 inhibitors. X-ray structures have played a significant role in orienting the chemistry effort in the initial phase of hit confirmation. Disclosure of an unconventional binding mode for 1 and 2, as demonstrated by X-ray crystallography, is presented and was an important factor in selecting and advancing a lead series. (C) 2017 Elsevier Ltd. All rights reserved.
• Design and Synthesis of Novel Aminoindazole-pyrrolo[2,3-b]pyridine Inhibitors of IKKα That Selectively Perturb Cellular Non-Canonical NF-κB Signalling
  作者：Christopher Riley、Usama Ammar、Aisha Alsfouk、Nahoum G. Anthony、Jessica Baiget、Giacomo Berretta、David Breen、Judith Huggan、Christopher Lawson、Kathryn McIntosh、Robin Plevin、Colin J. Suckling、Louise C. Young、Andrew Paul、Simon P. Mackay

  DOI：10.3390/molecules29153515

  日期：——

  The inhibitory-kappaB kinases (IKKs) IKKα and IKKβ play central roles in regulating the non-canonical and canonical NF-κB signalling pathways. Whilst the proteins that transduce the signals of each pathway have been extensively characterised, the clear dissection of the functional roles of IKKα-mediated non-canonical NF-κB signalling versus IKKβ-driven canonical signalling remains to be fully elucidated. Progress has relied upon complementary molecular and pharmacological tools; however, the lack of highly potent and selective IKKα inhibitors has limited advances. Herein, we report the development of an aminoindazole-pyrrolo[2,3-b]pyridine scaffold into a novel series of IKKα inhibitors. We demonstrate high potency and selectivity against IKKα over IKKβ in vitro and explain the structure–activity relationships using structure-based molecular modelling. We show selective target engagement with IKKα in the non-canonical NF-κB pathway for both U2OS osteosarcoma and PC-3M prostate cancer cells by employing isoform-related pharmacodynamic markers from both pathways. Two compounds (SU1261 [IKKα Ki = 10 nM; IKKβ Ki = 680 nM] and SU1349 [IKKα Ki = 16 nM; IKKβ Ki = 3352 nM]) represent the first selective and potent pharmacological tools that can be used to interrogate the different signalling functions of IKKα and IKKβ in cells. Our understanding of the regulatory role of IKKα in various inflammatory-based conditions will be advanced using these pharmacological agents.