6-溴-2-(4-硝基苯基)-咪唑并[1,2-a]吡啶 | 321945-25-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 6-溴-2-(4-硝基苯基)-咪唑并[1,2-a]吡啶
• 中文别名: 5-({2-[二(吡啶-2-基甲基)氨基]乙基}氨基)-2-(6-羟基-3-羰基-3H-占吨-9-基)苯甲酸
• 英文名称: 6-bromo-2-(4-nitrophenyl)imidazo[1,2-a]pyridine
• CAS: 321945-25-9
• 化学式: C₁₃H₈BrN₃O₂
• mdl: MFCD00430184
• 分子量: 318.129
• InChiKey: AADWKSKCFXJLFW-UHFFFAOYSA-N

物化性质

• 熔点：
  >250 °C(Solv: pyridine (110-86-1))
• 密度：
  1.67±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-溴-2-(4-硝基苯基)-咪唑并[1,2-a]吡啶 在 铁粉 、 氯化铵 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 生成 4-(6-Bromoimidazo[1,2-a]pyridin-2-yl)phenylamine
  参考文献：
  名称：

  Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N′-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo

  摘要：

  FLT3 inhibitors have been explored as a viable therapy for acute myeloid leukemia (AML). However, the clinical outcomes of these FLT3 inhibitors were underwhelming except AC220. Therefore, the development of novel FLT3 inhibitors with high potency against both FLT3-WT and FLT3-ITD mutants are strongly demanded at the present time. In this study, we designed and synthesized a series of novel N-(5-(tert-butyl) isoxazol-3-yl)-N'-phenylurea derivatives as FLT3 inhibitors. SAR studies focused on the fused rings led to the discovery of a series of compounds with high potency against FLT3-ITD-bearing MV4-11 cells and significantly inhibitory activity toward FLT3. Among these compounds, N-(5-(tert-butyl) isoxazol-3-yl)-N'-(4-(7-methoxyimidazo[1,2-a]pyridin-2-yl)phenyl) urea (16i), displayed acceptable aqueous solubility, desirable pharmacokinetic profile and high cytotoxicity selectivity against MV4-11 cells. This compound can inhibit phosphorylation of FLT3 and induce apoptosis in a concentration-dependent manner. Further in vivo antitumor studies showed that 16i led to complete tumor regression in the MV4-11 xenograft model at a dose of 60 mg/kg/d while without observable body weight loss. This study had provided us a new chemotype of FLT3 inhibitors as novel therapic candidates for AML. (C) 2015 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2015.06.033
• 作为产物：
  描述：

  2-氨基-5-溴吡啶 、 2-溴-4'-硝基苯乙酮 在 碳酸氢钠 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 6-溴-2-(4-硝基苯基)-咪唑并[1,2-a]吡啶
  参考文献：
  名称：

  sp 3-和sp 2-杂化CH键的氧化交叉偶联：咪唑并[1,2- a ]吡啶的钒催化氨甲基化

  摘要：

  已经实现了取代的2-芳基咪唑并[1,2- a ]吡啶对N-甲基吗啉氧化物的钒催化氧化偶联，N-甲基吗啉既是偶联剂又是氧化剂。该反应用于各种取代的咪唑并[1,2- a ]吡啶和吲哚底物，产率高达90％。机理研究表明该反应可以通过曼尼希型过程进行。这项工作证明了如何将氧化氨基甲基化用作将叔胺引入杂环的有用方法，从而为常规曼尼希型反应提供了另一种方法。

  DOI：

  10.1021/acs.orglett.5b02539

文献信息

• Oxidative Cross-Coupling of sp³- and sp²-Hybridized C–H Bonds: Vanadium-Catalyzed Aminomethylation of Imidazo[1,2-<i>a</i>]pyridines
  作者：Pinku Kaswan、Ashley Porter、Kasiviswanadharaju Pericherla、Marissa Simone、Sean Peters、Anil Kumar、Brenton DeBoef

  DOI：10.1021/acs.orglett.5b02539

  日期：2015.11.6

  The vanadium-catalyzed oxidative coupling of substituted 2-arylimidiazo[1,2-a]pyridines to N-methylmorpholine oxide, which acts as both a coupling partner and an oxidant, has been achieved. This reaction was applied to various substituted imidiazo[1,2-a]pyridine and indole substrates, resulting in yields as high as 90%. Mechanistic investigations indicate that the reaction may proceed via a Mannich-type

  已经实现了取代的2-芳基咪唑并[1,2- a ]吡啶对N-甲基吗啉氧化物的钒催化氧化偶联，N-甲基吗啉既是偶联剂又是氧化剂。该反应用于各种取代的咪唑并[1,2- a ]吡啶和吲哚底物，产率高达90％。机理研究表明该反应可以通过曼尼希型过程进行。这项工作证明了如何将氧化氨基甲基化用作将叔胺引入杂环的有用方法，从而为常规曼尼希型反应提供了另一种方法。
• Hydrazone derivative
  申请人：Kawagoe Keiichi

  公开号：US20060276433A1

  公开（公告）日：2006-12-07

  A compound represented by the following formula (I): wherein R 1 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R 2 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R 3 represents hydrogen, etc.; Ar represents a divalent group derived from aromatic hydrocarbon, etc.; X represents a single bond, linear or branched alkylene having from 1 to 3 carbon atoms which may have a substituent, etc.; and G represents halogen, a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc., a salt thereof or a solvate thereof; and an agent for inhibiting aggregation and/or deposition of an amyloid protein or an amyloid-like protein, which comprises the compound, a salt thereof or a solvate thereof.

  以下是式子（I）所代表的化合物： 其中，R1代表氢、芳基（可能带有取代基）、饱和或不饱和的5-至7-成员杂环基（可能带有取代基）等； R2代表氢、芳基（可能带有取代基）、饱和或不饱和的5-至7-成员杂环基（可能带有取代基）等； R3代表氢等； Ar代表从芳香族碳氢化合物衍生的二价基团等； X代表单键、线性或支链烷基，具有1至3个碳原子，可能带有取代基等； G代表卤素、饱和或不饱和的5-或6-成员环烃基（可能带有取代基）、饱和或不饱和的5-至7-成员杂环基（可能带有取代基）等，其盐或溶剂化物；以及用于抑制淀粉样蛋白或类淀粉样蛋白的聚集和/或沉积的药剂，包括该化合物、其盐或溶剂化物。
• Synthesis and Evaluation of Photophysical Properties of C‐3 Halogenated Derivatives of <scp>2‐Phenylimidazo</scp> [1,2‐ <i>a</i> ]pyridine
  作者：Hong Chen、Yanyan Wang、Qingjie Liu、Yanchun Guo、Shuxia Cao、Yufen Zhao

  DOI：10.1002/cjoc.202200224

  日期：2022.10

  A CuX-mediated regioselective halogenation reaction of 2-phenylimidazo[1,2-a]pyridine in the presence of oxygen is introduced in this paper. This reaction provides an effective method for the production of C-3 halogenated 2-phenylimidazo[1,2-a]pyridines with a yield of up to 96%. A plausible mechanism for the formation of title compounds via 2-phenylimidazo[1,2-a]pyridine–CuX complex intermediate is

  本文介绍了CuX介导的2-苯基咪唑并[1,2- a ]吡啶在氧气存在下的区域选择性卤化反应。该反应为生产C-3卤代2-苯基咪唑并[1,2- a ]吡啶提供了一种有效的方法，收率高达96%。提出了一种通过 2-苯基咪唑并[1,2- a ]吡啶-CuX 络合物中间体形成标题化合物的合理机制。代表性化合物的结构是通过单晶XRD方法建立的。通过 Hirshfeld 表面分析和 DFT 计算证实的电子结构合理化了相关吸收和发射的特征以及大的斯托克斯位移。
• HYDRAZONE DERIVATIVE
  申请人：DAIICHI PHARMACEUTICAL CO., LTD.

  公开号：EP1612204A1

  公开（公告）日：2006-01-04

  A compound represented by the following formula (I): wherein R1 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R2 represents hydrogen, aryl which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc.; R3 represents hydrogen, etc.; Ar represents a divalent group derived from aromatic hydrocarbon, etc.; X represents a single bond, linear or branched alkylene having from 1 to 3 carbon atoms which may have a substituent, etc.; and G represents halogen, a saturated or unsaturated 5- or 6-membered cyclic hydrocarbon group which may have a substituent, a saturated or unsaturated 5- to 7-membered heterocyclic group which may have a substituent, etc., a salt thereof or a solvate thereof; and an agent for inhibiting aggregation and/or deposition of an amyloid protein or an amyloid-like protein, which comprises the compound, a salt thereof or a solvate thereof

  下式(I)所代表的化合物： 其中 R1 代表氢、可能具有取代基的芳基、可能具有取代基的饱和或不饱和 5 至 7 元杂环基团等；R2 代表氢、可能具有取代基的芳基、可能具有取代基的饱和或不饱和 5 至 7 元杂环基团等；R3 代表氢等。Ar 代表衍生自芳香烃的二价基团等；X 代表具有 1 至 3 个碳原子的单键、线性或支链亚烷基（可具有取代基）等；G 代表卤素、饱和或不饱和的 5 或 6 元环状烃基（可具有取代基）、饱和或不饱和的 5 至 7 元杂环基（可具有取代基）等、一种抑制淀粉样蛋白或类淀粉样蛋白聚集和/或沉积的制剂，其中包括该化合物、其盐或其溶液。
• Discovery of novel N-(5-(tert-butyl)isoxazol-3-yl)-N′-phenylurea analogs as potent FLT3 inhibitors and evaluation of their activity against acute myeloid leukemia in vitro and in vivo
  作者：Ying Xu、Ning-Yu Wang、Xue-Jiao Song、Qian Lei、Ting-Hong Ye、Xin-Yu You、Wei-Qiong Zuo、Yong Xia、Li-Dan Zhang、Luo-Ting Yu

  DOI：10.1016/j.bmc.2015.06.033

  日期：2015.8

  FLT3 inhibitors have been explored as a viable therapy for acute myeloid leukemia (AML). However, the clinical outcomes of these FLT3 inhibitors were underwhelming except AC220. Therefore, the development of novel FLT3 inhibitors with high potency against both FLT3-WT and FLT3-ITD mutants are strongly demanded at the present time. In this study, we designed and synthesized a series of novel N-(5-(tert-butyl) isoxazol-3-yl)-N'-phenylurea derivatives as FLT3 inhibitors. SAR studies focused on the fused rings led to the discovery of a series of compounds with high potency against FLT3-ITD-bearing MV4-11 cells and significantly inhibitory activity toward FLT3. Among these compounds, N-(5-(tert-butyl) isoxazol-3-yl)-N'-(4-(7-methoxyimidazo[1,2-a]pyridin-2-yl)phenyl) urea (16i), displayed acceptable aqueous solubility, desirable pharmacokinetic profile and high cytotoxicity selectivity against MV4-11 cells. This compound can inhibit phosphorylation of FLT3 and induce apoptosis in a concentration-dependent manner. Further in vivo antitumor studies showed that 16i led to complete tumor regression in the MV4-11 xenograft model at a dose of 60 mg/kg/d while without observable body weight loss. This study had provided us a new chemotype of FLT3 inhibitors as novel therapic candidates for AML. (C) 2015 Published by Elsevier Ltd.