1-(prop-2-yn-1-yl)imidazole-2-carbaldehyde | 1247894-26-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(prop-2-yn-1-yl)imidazole-2-carbaldehyde
• 英文别名: 1-(3-prop-2-yn-1-yl)imidazole-2-carbaldehyde；1-(prop-2-yn-1-yl)-1H-imidazole-2-carbaldehyde；1H-Imidazole-2-carboxaldehyde, 1-(2-propyn-1-yl)-；1-prop-2-ynylimidazole-2-carbaldehyde
• CAS: 1247894-26-3
• 化学式: C₇H₆N₂O
• mdl: MFCD16695424
• 分子量: 134.137
• InChiKey: AHOSJXZFHMJEHE-UHFFFAOYSA-N

物化性质

• 沸点：
  281.7±42.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.142
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(prop-2-yn-1-yl)imidazole-2-carbaldehyde 在 盐酸羟胺 、 sodium carbonate 作用下， 以 水 为溶剂， 反应 1.0h， 以78%的产率得到1-(prop-2-yn-1-yl)imidazole-2-carbaldehyde oxime
  参考文献：
  名称：

  [EN] CATALYTIC SCAVENGERS OF ORGANOPHOSPHATES TO POTENTIATE BUTYRYLCHOLINESTERASE (BCHE) AS A CATALYTIC BIOSCAVENGER AND METHODS FOR MAKING AND USING THEM
  [FR] PIÉGEURS CATALYTIQUES D'ORGANOPHOSPHATES POUR POTENTIALISER LA BUTYRYLCHOLINESTÉRASE (HBCHE)

  摘要：

  提供了N-烷基咪唑-2-醛肟，包括阳离子咪唑盐和不带电的三级咪唑醛肟，以及制备和使用它们的组合物和方法，包括重新激活被有机磷酸酯（OP）抑制的人丁酰胆碱酯酶（hBChE）或乙酰胆碱酯酶（hAChE）的方法。通过给予本发明的组合物，不活性或结合的hBChE-OP或hAChE-OP被重新激活，完成了OP的催化周转和失活循环；在替代实施方案中，可逆保护hBChE和hAChE免受OP不可逆失活的次要机制以及再激活组织AChE也有助于整体功效。

  公开号：

  WO2015057822A1
• 作为产物：
  描述：

  3-溴丙炔 、 2-咪唑甲醛 在 lithium bromide monohydrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 10.5h， 以29%的产率得到1-(prop-2-yn-1-yl)imidazole-2-carbaldehyde
  参考文献：
  名称：

  动态组合化学中配体发现的多主题探针的候选者

  摘要：

  多功能化材料有望成为发现配体和目标生物材料之间特定相互作用的通用探针。因此，需要有效的方法来制备功能的可能组合。动态组合化学 (DCC) 的概念非常适合生成任何可能的组合，以及筛选目标生物材料。在这里，我们提出了一种新的多主题探针分子设计，用于 DCC 中的配体发现。我们合成了一种新的山墙卟啉 GP1，它具有 prop-2-yne 基团作为支架来引入各种功能基团。GP1 是通过 1,3-亚苯基部分连接的双（咪唑基卟啉锌）化合物，它通过强大的咪唑-锌互补配位自发和定量地产生大环。一些不同类型的官能团以高产率被引入 GP1。由具有不同类型取代基的 GP1 衍生物组成的异质大环的形成是在平衡条件下完成的。这些结果承诺，当 GP 组分的种类增加时，可以提供大量具有各种官能团的大环。这些特征是 DCC 所需要的，并且使用 GP1 的本系统是一个潜在的候选者，可提供多主题探针的动态组合库，以发现配体和

  DOI：

  10.3390/molecules24112166

文献信息

• CATALYTIC SCAVENGERS OF ORGANOPHOSPHATES TO POTENTIATE BUTYRYLCHOLINESTERASE (hBChE) AS A CATALYTIC BIOSCAVENGER AND METHODS FOR MAKING AND USING THEM
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20160256438A1

  公开（公告）日：2016-09-08

  Provided are N-alkyl imidazole 2-aldoximes, including cationic imidazolium and uncharged tertiary imidazole aldoximes, and compositions and methods for making and using them, including methods for reactivating human butyrylcholinesterase (hBChE) or acetylcholinesterase (hAChE) inhibited by organophosphate (OP). By administration of a composition of the invention, the inactive or conjugated hBChE-OP or hAChE-OP is reactivated and the catalytic cycle of turnover and inactivation of the OP is completed; and in alternative embodiments, secondary mechanisms of reversible protection of hBChE and hAChE from irreversible inactivation by OPs and reactivation of tissue AChE also contribute to overall efficacy.

  提供了N-烷基咪唑-2-醛肟，包括阳离子咪唑和不带电的三级咪唑醛肟，以及制备和使用它们的组合物和方法，包括重新激活被有机磷酸酯（OP）抑制的人丁酰胆碱酯酶（hBChE）或乙酰胆碱酯酶（hAChE）的方法。通过使用本发明的组合物，不活性或结合的hBChE-OP或hAChE-OP被重新激活，完成OP的催化循环和失活；在替代实施方案中，可逆保护hBChE和hAChE免受OP不可逆失活的次要机制以及组织AChE的重新激活也有助于总体功效。
• Catalytic scavengers of organophosphates to potentiate butyrylcholinesterase (hBChE) as a catalytic bioscavenger and methods for making and using them
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US10172831B2

  公开（公告）日：2019-01-08

  Provided are N-alkyl imidazole 2-aldoximes, including cationic imidazolium and uncharged tertiary imidazole aldoximes, and compositions and methods for making and using them, including methods for reactivating human butyrylcholinesterase (hBChE) or acetylcholinesterase (hAChE) inhibited by organophosphate (OP). By administration of a composition of the invention, the inactive or conjugated hBChE-OP or hAChE-OP is reactivated and the catalytic cycle of turnover and inactivation of the OP is completed; and in alternative embodiments, secondary mechanisms of reversible protection of hBChE and hAChE from irreversible inactivation by OPs and reactivation of tissue AChE also contribute to overall efficacy.

  本发明提供了N-烷基咪唑2-醛肟，包括阳离子咪唑鎓和不带电的叔咪唑醛肟，以及制造和使用它们的组合物和方法，包括重新激活被有机磷（OP）抑制的人丁酰胆碱酯酶（hBChE）或乙酰胆碱酯酶（hAChE）的方法。通过施用本发明的组合物，无活性或共轭的 hBChE-OP 或 hAChE-OP 被重新激活，OP 的周转和失活催化循环完成；在另一个实施方案中，可逆保护 hBChE 和 hAChE 免受 OP 的不可逆失活以及重新激活组织 AChE 的次级机制也有助于提高整体疗效。
• New Structural Scaffolds for Centrally Acting Oxime Reactivators of Phosphylated Cholinesterases
  作者：Rakesh K. Sit、Zoran Radić、Valeria Gerardi、Limin Zhang、Edzna Garcia、Maja Katalinić、Gabriel Amitai、Zrinka Kovarik、Valery V. Fokin、K. Barry Sharpless、Palmer Taylor

  DOI：10.1074/jbc.m111.230656

  日期：2011.6

  We describe here the synthesis and activity of a new series of oxime reactivators of cholinesterases (ChEs) that contain tertiary amine or imidazole protonatable functional groups. Equilibration between the neutral and protonated species at physiological pH enables the reactivators to cross the blood-brain barrier and distribute in the CNS aqueous space as dictated by interstitial and cellular pH values. Our structure-activity analysis of 134 novel compounds considers primarily imidazole aldoximes and N-substituted 2-hydroxyiminoacetamides. Reactivation capacities of novel oximes are rank ordered by their relative reactivation rate constants at 0.67 mM compared with 2-pyridinealdoxime methiodide for reactivation of four organophosphate (sarin, cyclosarin, VX, and paraoxon) conjugates of human acetylcholinesterase (hAChE). Rank order of the rates differs for reactivation of human butyrylcholinesterase (hBChE) conjugates. The 10 best reactivating oximes, predominantly hydroxyimino acetamide derivatives (for hAChE) and imidazole-containing aldoximes (for hBChE) also exhibited reasonable activity in the reactivation of tabun conjugates. Reactivation kinetics of the lead hydroxyimino acetamide reactivator of hAChE, when analyzed in terms of apparent affinity (1/K-ox) and maximum reactivation rate (k(2)), is superior to the reference uncharged reactivators monoisonitrosoacetone and 2,3-butanedione monoxime and shows potential for further refinement. The disparate pH dependences for reactivation of ChE and the general base-catalyzed oximolysis of acetylthiocholine reveal that distinct reactivator ionization states are involved in the reactivation of ChE conjugates and in conferring nucleophilic reactivity of the oxime group.
• Imidazole Aldoximes Effective in Assisting Butyrylcholinesterase Catalysis of Organophosphate Detoxification
  作者：Rakesh K. Sit、Valery V. Fokin、Gabriel Amitai、K. Barry Sharpless、Palmer Taylor、Zoran Radić

  DOI：10.1021/jm401650z

  日期：2014.2.27

  Intoxication by organophosphate (OP) nerve agents and pesticides should be addressed by efficient, quickly deployable countermeasures such as antidotes reactivating acetylcholinesterase or scavenging the parent OP. We present here synthesis and initial in vitro characterization of 14 imidazole aldoximes and their structural refinement into three efficient reactivators of human butyrylcholinesterase (hBChE) inhibited covalently by nerve agent OPs, sarin, cyclosarin, VX, and the OP pesticide metabolite, paraoxon. Rapid reactivation of OP-hBChE conjugates by uncharged and nonprotonated tertiary imidazole aldoximes allows the design of a new OP countermeasure by conversion of hBChE from a stoichiometric to catalytic OP bioscavenger with the prospect of oral bioavailability and central nervous system penetration. The enhanced in vitro reactivation efficacy determined for tertiary imidazole aldoximes compared to that of their quaternary N-methyl imidazolium analogues is attributed to ion pairing of the cationic imidazolium with Asp 70, altering a reactive alignment of the aldoxime with the phosphorus in the OP-hBChE conjugate.
• CATALYTIC SCAVENGERS OF ORGANOPHOSPHATES TO POTENTIATE BUTYRYLCHOLINESTERASE (BCHE) AS A CATALYTIC BIOSCAVENGER AND METHODS FOR MAKING AND USING THEM
  申请人：The Regents of the University of California

  公开号：EP3057582A1

  公开（公告）日：2016-08-24