6-bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine

• 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: 6-bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine
• 英文别名: 6-Bromo-2-(chloromethyl)-3-nitroimidazo[1,2-a]pyridine
• 化学式: C₈H₅BrClN₃O₂
• 分子量: 290.504
• InChiKey: RMHRTCYJCAYXMX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 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-bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine 在 四(三苯基膦)钯 sodium carbonate 作用下， 以 水 、 二甲基亚砜 为溶剂， 反应 6.0h， 生成 2-(4-chlorophenyl)sulfonylmethyl-3-nitro-6-[3-(trifluoromethyl)phenyl]imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Efficient Synthesis of New 8-Aryl Tricyclic Pyridinones

  摘要：

  以 6-溴-2-氯甲基-3-硝基咪唑并[1,2-a]吡啶为原料，通过四个步骤合成了新的三环吡啶酮，其中关键步骤包括铃木-宫浦交叉偶联反应和与酮丙二酸二乙酯的直接烯化反应。随后的一锅还原-环化反应提供了新的 8-芳基-2-氧代-1,2-二氢二吡啶并[1,2-a;3′,2′-d]咪唑-3-羧酸乙酯。

  DOI：

  10.1055/s-2006-942505
• 作为产物：
  描述：

  6-溴-2-(氯甲基)咪唑并[1,2-a]吡啶 在 硫酸 、 硝酸 作用下， 以100%的产率得到6-bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine
  参考文献：
  名称：

  Targeting the human parasite Leishmania donovani: Discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series

  摘要：

  We report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of Leishmania donovani, J774A. 1 murine and HepG2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). New derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying both a high potency (IC50 = 1.8 mu M) and a good selectivity index, in comparison with three antileishmanial reference drug-compounds (amphotericin B, miltefosine and pentamidine). Moreover, lead-compound 44 also exhibits good in vitro activity against the intracellular amastigote stage of L. donovani. Thus, the 6-halo-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine scaffold appears as a new promising selective antileishmanial pharmacophore, especially when substituted at position 8 by a bromine atom. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.002

文献信息

• Synthesis and Structural Characterization of Three Phenylsulfonyl Derivatives: Influence of Halogen Substituents on the Intermolecular Interactions
  作者：C. Castera、M. D. Crozet、M. Giorgi、P. Vanelle

  DOI：10.1007/s10870-007-9256-z

  日期：2007.11.7

  Synthesis and X-ray structural determination of three halogenated nitroimidazo[1,2-a]pyridine phenylsulfonyl derivatives are reported. (2) is monoclinic P21/c with a = 9.6679(1), b = 11.3642(2), c = 15.2189(2)Å, β = 105.9053(7)°; (3) is triclinic P −1 with a = 8.5556(2), b = 13.1191(3), c = 15.5132(4)Å, α = 76.0110(8), β = 89.1768(8), γ = 78.953(2)°; (4) is monoclinic P21/c with a = 15.3353(2), b = 8.8621(2), c = 11.4189(3)Å, β = 90.9704(7)°. In the title compounds that differ by the nature and number of halogen substituents, the arylsulfonyl moieties are oriented differently relatively to the nitroimidazopyridine. Moreover non-classical intermolecular interactions are revealed by the X-ray analysis. The X-ray structures of three halogenated nitroimidazo[1,2-a]pyridine phenylsulfonyl derivatives reveal different intermolecular interactions within the crystals. C. Castera, M. D. Crozet, M. Giorgi and P. Vanelle The X-ray structures of three halogenated nitroimidazo[1,2-a]pyridine phenylsulfonyl derivatives reveal different intermolecular interactions within the crystals. Synthesis and structural characterization of three phenylsulfonyl derivatives: influence of halogen substituents on the intermolecular interactions. C. Castera,1 M. D. Crozet,1 M. Giorgi,2 and P. Vanelle1* 1Laboratoire de Chimie Organique Pharmaceutique, UMR CNRS 6517, Université de la Méditerranée, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Marseille cedex 5, France ; 2Spectropôle-RX, Université Paul Cézanne Aix-Marseille III, Faculté des Sciences et Techniques, Avenue Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France.

  报告了三种卤代硝基咪唑并[1,2-a]吡啶苯磺酰衍生物的合成和 X 射线结构测定。(2)为单斜 P21/c，a = 9.6679(1)，b = 11.3642(2)，c = 15.2189(2)埃，β = 105.9053(7)°；(3)为三菱形 P-1，a = 8.5556(2)，b = 13.1191(3)，c = 15.5132(4)埃，α = 76.0110(8)，β = 89.1768(8)，γ = 78.953(2)°；（4）为单斜 P21/c，a = 15.3353(2)，b = 8.8621(2)，c = 11.4189(3)埃，β = 90.9704(7)°。在卤素取代基的性质和数量不同的标题化合物中，芳基磺酰基相对于硝基咪唑吡啶的取向不同。此外，X 射线分析还揭示了非典型的分子间相互作用。三种卤代硝基咪唑并[1,2-a]吡啶苯磺酰基衍生物的 X 射线结构揭示了晶体内部不同的分子间相互作用。C. Castera、M. D. Crozet、M. Giorgi 和 P. Vanelle 三种卤代硝基咪唑并[1,2-a]吡啶苯磺酰基衍生物的 X 射线结构揭示了晶体内部不同的分子间相互作用。三种苯磺酰基衍生物的合成与结构表征：卤素取代基对分子间相互作用的影响。C. Castera,1 M. D. Crozet,1 M. Giorgi,2 and P. Vanelle1* 1.Vanelle1* 1Laboratoire de Chimie Organique Pharmaceutique, UMR CNRS 6517, Université de la Méditerranée, Faculté de Pharmacie, 27 Boulevard Jean Moulin, 13385 Marseille cedex 5, France; 2Spectropôle-RX, Université Paul Cézanne Aix-Marseille III, Faculté des Sciences et Techniques, Avenue Escadrille Normandie-Niemen, 13397 Marseille cedex 20, France.
• An Efficient Synthetic Route to New Imidazo[1,2-a]pyridines by Cross-Coupling Reactions in Aqueous Medium
  作者：Patrice Vanelle、Caroline Castera、Maxime D. Crozet

  DOI：10.3987/com-05-10548

  日期：——
• Rapid Synthesis of New Azaheterocyclic Hydroxymalonate Derivatives Using TDAE Approach
  作者：Patrice Vanelle、Marc Montana、Maxime D. Crozet、Caroline Castera-Ducros、Thierry Terme、Patrice Vanelle

  DOI：10.3987/com-07-11264

  日期：——
• Targeting the human parasite Leishmania donovani: Discovery of a new promising anti-infectious pharmacophore in 3-nitroimidazo[1,2-a]pyridine series
  作者：Caroline Castera-Ducros、Lucie Paloque、Pierre Verhaeghe、Magali Casanova、Christophe Cantelli、Sébastien Hutter、Floriane Tanguy、Michèle Laget、Vincent Remusat、Anita Cohen、Maxime D. Crozet、Pascal Rathelot、Nadine Azas、Patrice Vanelle

  DOI：10.1016/j.bmc.2013.09.002

  日期：2013.11

  We report herein the discovery of antileishmanial molecules based on the imidazo[1,2-a]pyridine ring. In vitro screenings of imidazopyridines belonging to our chemical library, toward the promastigotes stage of Leishmania donovani, J774A. 1 murine and HepG2 human cells, permitted to identify three selective hit-compounds (12, 20 and 28). New derivatives were then synthesized to allow structure-activity and -toxicity relationships analyses, enabling to characterize a lead-compound (44) displaying both a high potency (IC50 = 1.8 mu M) and a good selectivity index, in comparison with three antileishmanial reference drug-compounds (amphotericin B, miltefosine and pentamidine). Moreover, lead-compound 44 also exhibits good in vitro activity against the intracellular amastigote stage of L. donovani. Thus, the 6-halo-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine scaffold appears as a new promising selective antileishmanial pharmacophore, especially when substituted at position 8 by a bromine atom. (C) 2013 Elsevier Ltd. All rights reserved.
• Efficient Synthesis of New 8-Aryl Tricyclic Pyridinones
  作者：Patrice Vanelle、Caroline Castera-Ducros、Maxime Crozet

  DOI：10.1055/s-2006-942505

  日期：2006.8

  New tricyclic pyridinones were synthesized from 6-bromo-2-chloromethyl-3-nitroimidazo[1,2-a]pyridine in four steps involving a Suzuki-Miyaura cross-coupling reaction and a direct olefination with diethyl ketomalonate as key steps. Subsequent one-pot reduction-cyclization provided new ethyl 8-aryl-2-oxo-1,2-dihydrodipyrido[1,2-a;3′,2′-d]imidazole-3-carboxylates.

  以 6-溴-2-氯甲基-3-硝基咪唑并[1,2-a]吡啶为原料，通过四个步骤合成了新的三环吡啶酮，其中关键步骤包括铃木-宫浦交叉偶联反应和与酮丙二酸二乙酯的直接烯化反应。随后的一锅还原-环化反应提供了新的 8-芳基-2-氧代-1,2-二氢二吡啶并[1,2-a;3′,2′-d]咪唑-3-羧酸乙酯。