4-(6-chloro-1H-imidazo[4,5-c]pyridin-4-yl)morpholine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 4-(6-chloro-1H-imidazo[4,5-c]pyridin-4-yl)morpholine
• 英文别名: 4-(6-Chloro-1H-imidazo[4,5-c]pyridin-4-yl)morpholine
• 化学式: C₁₀H₁₁ClN₄O
• 分子量: 238.677
• InChiKey: JICICRMOXNWDLI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  54
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(6-chloro-1H-imidazo[4,5-c]pyridin-4-yl)morpholine 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 1.08h， 生成 4-(6-chloro-1-(methylsulfonylmethyl)-1H-imidazo[4,5-c]pyridin-4-yl)morpholine
  参考文献：
  名称：

  Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles (ABI) as ATR Inhibitors

  摘要：

  Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The ABI series was potent and selective for ATR. Incorporation of a 6-azaindole afforded a marked increase in cellular potency but was associated with poor PK and hERG ion channel inhibition. DMPK experiments established that CYP P450 and AO metabolism in conjunction with Pgp and BCRP efflux were major causative mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability driven by the presence of both a morpholine and an indole moiety. Incorporation of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the various medicinal chemistry issues encountered.

  DOI：

  10.1021/ml500352s
• 作为产物：
  描述：

  4-氨基-2,6-二氯-3-硝基吡啶嘧啶 在 氢气 、 乙酸酐 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 异丙醇 为溶剂， 反应 9.25h， 生成 4-(6-chloro-1H-imidazo[4,5-c]pyridin-4-yl)morpholine
  参考文献：
  名称：

  Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles (ABI) as ATR Inhibitors

  摘要：

  Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The ABI series was potent and selective for ATR. Incorporation of a 6-azaindole afforded a marked increase in cellular potency but was associated with poor PK and hERG ion channel inhibition. DMPK experiments established that CYP P450 and AO metabolism in conjunction with Pgp and BCRP efflux were major causative mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability driven by the presence of both a morpholine and an indole moiety. Incorporation of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the various medicinal chemistry issues encountered.

  DOI：

  10.1021/ml500352s

文献信息

• BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS
  申请人：AVERSA Robert

  公开号：US20160038504A1

  公开（公告）日：2016-02-11

  The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

  本发明提供了式（I）所述的化合物及其盐，并且提供了这些化合物用于治疗与Raf激酶活性相关的疾病的治疗用途。本发明还提供了包含这些化合物的制药组合物，以及包含这些化合物和治疗联合剂的组合物。
• Biaryl amide compounds as kinase inhibitors
  申请人：NOVARTIS AG

  公开号：US10245267B2

  公开（公告）日：2019-04-02

  The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.

  本发明提供了本文所述的式(I)化合物及其盐类，以及这些化合物治疗与Raf激酶活性相关疾病的治疗用途。本发明进一步提供了包含这些化合物的药物组合物，以及包含这些化合物和一种治疗辅助试剂的组合物。
• US9694016B2
  申请人：——

  公开号：US9694016B2

  公开（公告）日：2017-07-04
• [EN] BIARYL AMIDE COMPOUNDS AS KINASE INHIBITORS<br/>[FR] COMPOSÉS BIARYLE AMIDES EN TANT QU'INHIBITEURS DE KINASE
  申请人：NOVARTIS AG

  公开号：WO2014151616A1

  公开（公告）日：2014-09-25

  The present invention provides compounds of Formula (I) as described herein, and salts thereof, and therapeutic uses of these compounds for treatment of disorders associated with Raf kinase activity. The invention further provides pharmaceutical compositions comprising these compounds, and compositions comprising these compounds and a therapeutic co-agent.
• Structure-Based Drug Design of Novel, Potent, and Selective Azabenzimidazoles (ABI) as ATR Inhibitors
  作者：Paul A Barsanti、Yue Pan、Yipin Lu、Rama Jain、Matthew Cox、Robert J. Aversa、Michael P. Dillon、Robert Elling、Cheng Hu、Xianming Jin、Mark Knapp、Jiong Lan、Savithri Ramurthy、Patrick Rudewicz、Lina Setti、Sharadha Subramanian、Michelle Mathur、Lorena Taricani、George Thomas、Linda Xiao、Qin Yue

  DOI：10.1021/ml500352s

  日期：2015.1.8

  Compound 13 was discovered through morphing of the ATR biochemical HTS hit 1. The ABI series was potent and selective for ATR. Incorporation of a 6-azaindole afforded a marked increase in cellular potency but was associated with poor PK and hERG ion channel inhibition. DMPK experiments established that CYP P450 and AO metabolism in conjunction with Pgp and BCRP efflux were major causative mechanisms for the observed PK. The series also harbored the CYP3A4 TDI liability driven by the presence of both a morpholine and an indole moiety. Incorporation of an adjacent fluorine or nitrogen into the 6-azaindole addressed many of the various medicinal chemistry issues encountered.