N-[3-(氨甲基)苄基]乙脒 | 180001-34-7

• 物质功能分类: 化学试剂 - 有机试剂 - 亚氨、脒
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[3-(氨甲基)苄基]乙脒
• 英文名称: N-(3-(aminomethyl)benzyl)acetimidine
• 英文别名: 1400W；N-(3-(aminomethyl)benzyl)-acetamidine；N-(3-(Aminomethyl)benzyl)acetamidine；N'-[[3-(aminomethyl)phenyl]methyl]ethanimidamide
• CAS: 180001-34-7
• 化学式: C₁₀H₁₅N₃
• mdl: MFCD01317835
• 分子量: 177.249
• InChiKey: RODUKNYOEVZQPR-UHFFFAOYSA-N

物化性质

• 熔点：
  208-220 °C
• 沸点：
  301.7±44.0 °C(Predicted)
• 密度：
  1.09±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二甲基亚砜、甲醇、水
• 稳定性/保质期：

  避免水分和空气

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 安全说明：
  S22,S24/25
• WGK Germany：
  3
• 储存条件：
  保存方法：在4°C以下的环境中密闭保存。

反应信息

• 作为反应物：
  描述：

  N-[3-(氨甲基)苄基]乙脒 在 N-甲基吗啉 、 盐酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.25h， 生成 {1-[(3-{[(2-ammonio-3-mercaptopropanoyl)amino]methyl}benzyl)amino]ethylidene}ammonium dichloride
  参考文献：
  名称：

  N- {3-[（（亚氨基酰亚胺基氨基）甲基]苄基} -1-脯氨酰胺二盐酸盐的发现：诱导型一氧化氮合酶的新型有效和选择性抑制剂，可作为治疗恶性神经胶质瘤的有前途的药物。

  摘要：

  在哺乳动物细胞中，异常的iNOS诱导可能会产生有害的后果，并且似乎参与了诸如恶性神经胶质瘤等不同肿瘤的增殖和发展。因此，对iNOS的选择性抑制可能代表了治疗这些疾病的可行治疗策略。在这种情况下，我们先前已经公开了新的乙am，它们能够以比eNOS或nNOS很高的选择性抑制iNOS。在这里，我们报告了与N-[（3-氨基甲基）苄基]乙（1400 W）的领先支架在结构上相关的一系列新化合物的合成，以及它们的体外活性和选择性。化合物39作为该系列中最有希望的分子出现，并在离体和灌注的抗性动脉上进行了离体评估，证实了对iNOS抑制的高度选择性。此外，研究了C6大鼠神经胶质瘤细胞系对39种生物的生物学反应，初步的MTT分析显示C6大鼠神经胶质瘤细胞的细胞代谢活性显着降低。最后，对接研究的结果阐明了39与NOS催化位点的结合方式。

  DOI：

  10.1016/j.ejmech.2018.04.027
• 作为产物：
  描述：

  N-[3-(氨基甲基)苄基]氨基甲酸叔丁酯 在 盐酸 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 6.0h， 生成 N-[3-(氨甲基)苄基]乙脒
  参考文献：
  名称：

  Mechanism of Inactivation of Inducible Nitric Oxide Synthase by Amidines. Irreversible Enzyme Inactivation without Inactivator Modification

  摘要：

  Nitric oxide synthases (NOS) are hemoproteins that catalyze the reaction Of L-arginine to L-Citrulline and nitric oxide. N-(3-(Aminomethyl)benzyl)acetamidine (1400W) was reported to be a slow, tight-binding, and highly selective inhibitor of iNOS in vitro and in vivo. Previous mechanistic studies reported that 1400W was recovered quantitatively after iNOS fully lost its activity and modification to iNOS was not detected. Here, it is shown that 1400W is a time-, concentration-, and NADPH-dependent irreversible inactivator of iNOS. HPLC-electrospray mass spectrometric analysis of the incubation mixture of iNOS with 1400W shows both loss of heme cofactor and formation of bilivedin, as was previously observed for iNOS inactivation by another amidine-containing compound, N-5(1-iminoethyl)-L-ornithine (L-NIO). The amount of biliverdin produced corresponds to the amount of heme lost by 1400W inactivation of iNOS. A convenient MS/MS-HPLC methodology was developed to identify the trace amount of biliverdin produced by inactivation of iNOS with either 1400W or L-NIO to be biliverdin \Xalpha out of the four possible regioisomers. Two mechanisms were previously proposed for iNOS inactivation by L-NIO: (1) uncoupling of the heme peroxide intermediate, leading to destruction of the heme to biliverdin; (2) abstraction of a hydrogen atom from the amidine methyl group followed by attachment to the heme cofactor, which causes the enzyme to catalyze the heme oxygenase reaction. The second mechanistic proposal was ruled out by inactivation of iNOS with d(3)-1400W, which produced no d(2)-1400W. Detection of carbon monoxide as one of the heme-degradation products further excludes the covalent heme adduct mechanism. On the basis of these results, a third mechanism is proposed in which the amidine inactivators of iNOS bind as does substrate L-arginine, but because of the amidine methyl group, the heme peroxy intermediate cannot be protonated, thereby preventing its conversion to the heme oxo intermediate. This leads to a change in the enzyme mechanism to one that resembles that of heme oxygenase, an enzyme known to convert heme to biliverdin \Xalpha.. This appears to be the first example of a compound that causes irreversible inactivation of an enzyme without itself becoming modified in any way.

  DOI：

  10.1021/ja0445645

文献信息

• Modulators of Cystic Fibrosis Transmembrane Conductance Regulator
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20160095858A1

  公开（公告）日：2016-04-07

  The present invention features a compound of formula I: or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , W, X, Y, Z, n, o, p, and q are defined herein, for the treatment of CFTR mediated diseases, such as cystic fibrosis. The present invention also features pharmaceutical compositions, method of treating, and kits thereof.

  本发明涉及一种具有以下化学式I的化合物： 或其药用可接受的盐，其中R 1 ，R 2 ，R 3 ，W，X，Y，Z，n，o，p和q在此处定义，用于治疗CFTR介导的疾病，如囊性纤维化。本发明还涉及药物组合物、治疗方法和相关工具包。
• SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS
  申请人：Dahmann Georg

  公开号：US20130023502A1

  公开（公告）日：2013-01-24

  The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R 1 , R 2 , R 4 , R 3 , R 5 and R 6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.

  该发明涉及公式1中的新取代吡啶基嘧啶化合物， 其中环A是一个含有五个成员的饱和或不饱和碳环，该环可选地包含一个、两个或三个异原子，每个异原子独立地选自N、S和O组成， 其中R1、R2、R4、R3、R5和R6如权利要求书中所定义，并且环A进一步可选地被一个或两个进一步取代基取代，以及上述化合物的药用盐、二对映体、对映体、消旋体、水合物和溶剂化合物。
• [EN] HETEROCYCLIC COMPOUNDS, MEDICAMENTS CONTAINING SAID COMPOUNDS, USE THEREOF AND PROCESSES FOR THE PREPARATION THEREOF<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES, MÉDICAMENTS CONTENANT LESDITS COMPOSÉS, UTILISATION DE CEUX-CI ET PROCÉDÉS POUR LA PRÉPARATION DE CEUX-CI
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2013092674A1

  公开（公告）日：2013-06-27

  The present invention relates to compounds of general formula (I) and the tautomers and the salts thereof, particularly the pharmaceutically acceptable salts thereof with inorganic or organic acids and bases, which have valuable pharmacological properties, particularly an inhibitory effect on epithelial sodium channels, the use thereof for the treatment of diseases, particularly diseases of the lungs and airways.

  本发明涉及一般式(I)的化合物，以及其互变异构体和盐，特别是其与无机或有机酸和碱形成的药用盐，具有有价值的药理特性，特别是对上皮钠通道具有抑制作用，其用于治疗疾病，特别是肺部和气道疾病。
• [EN] SUBSTITUTED PYRIDINYL-PYRIMIDINES AND THEIR USE AS MEDICAMENTS<br/>[FR] PYRIDINYL-PYRIMIDINES SUBSTITUÉES ET LEUR UTILISATION EN TANT QUE MÉDICAMENTS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012101013A1

  公开（公告）日：2012-08-02

  The invention relates to new substituted pyridinyl-pyrimidines of formula 1 wherein ring A is a five-membered saturated or unsaturated carbocyclic ring which optionally comprises one, two or three heteroatoms each independently from each other selected from the group N, S and O, wherein R1, R2, R4, R3, R5 and R6 are defined as in claim 1 and wherein ring A is further optionally substituted by one or two further substituents and the pharmaceutically acceptable salts, diastereomers, enantiomers, racemates, hydrates and solvates of the aforementioned compounds.

  该发明涉及公式1中的新取代吡啶基嘧啶，其中环A是一个五元饱和或不饱和碳环，可选地包含一个、两个或三个异原子，每个异原子独立地选自N、S和O组，其中R1、R2、R4、R3、R5和R6如权利要求1中所定义，环A进一步可选地被一个或两个进一步取代基取代，以及上述化合物的药学上可接受的盐、二对映体、对映体、消旋体、水合物和溶剂化合物。
• 5-LIPOXYGENASE-ACTIVATING PROTEIN (FLAP) INHIBITORS
  申请人：Hutchinson H. John

  公开号：US20070105866A1

  公开（公告）日：2007-05-10

  Described herein are compounds and pharmaceutical compositions containing such compounds, which modulate the activity of 5-lipoxygenase-activating protein (FLAP). Also described herein are methods of using such FLAP modulators, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other leukotriene-dependent or leukotriene mediated conditions or diseases.

  本发明描述了调节5-脂氧合酶激活蛋白(FLAP)活性的化合物和含有该化合物的药物组合物。本发明还描述了单独使用和与其他化合物联合使用FLAP调节剂，用于治疗呼吸系统、心血管系统和其他白三烯依赖性或白三烯介导的状况或疾病。