C-ethoxycarbonyl-N-(2-chlorophenyl)hydrazonoyl chloride | 28317-49-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: C-ethoxycarbonyl-N-(2-chlorophenyl)hydrazonoyl chloride
• 英文别名: ethyl 2-chloro-2-(2-(2-chlorophenyl)hydrazono)acetate；chloro[(2-chlorophenyl)hydrazono]-acetic acid, ethyl ester；ethyl 2-chloro[(2-chlorophenyl)hydrazono]acetate；2-Chlor-2-(2-chlorphenylhydrazono)-essigsaeureethylester；Ethyl 2-chloro-2-[2-(2-chlorophenyl)hydrazono]-acetate；ethyl 2-chloro-2-[(2-chlorophenyl)hydrazinylidene]acetate
• CAS: 28317-49-9
• 化学式: C₁₀H₁₀Cl₂N₂O₂
• 分子量: 261.108
• InChiKey: LTPRVINQSYJPIR-UHFFFAOYSA-N

物化性质

• 熔点：
  90 °C(Solv: ethanol (64-17-5))
• 沸点：
  332.8±44.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  50.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  C-ethoxycarbonyl-N-(2-chlorophenyl)hydrazonoyl chloride 在 草酰氯 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  N-(4-Cyanotetrahydro-2H-pyran-4-yl) and N-(1-Cyanocyclohexyl) Derivatives of 1,5-Diarylpyrazole-3-carboxamides Showing High Affinity for 18 kDa Translocator Protein and/or Cannabinoid Receptors

  摘要：

  In order to develop improved radioligands for imaging brain CB(1) receptors with positron emission tomography (PET) based on rimonabant (5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide, 1), we synthesized compounds 9a-s in which the N-piperidinyl ring was replaced with a 4-(4-cyanotetrahydro-2H-pyranyl) or 1-cyanocyclohexyl ring. Such changes were expected to be almost isosteric with 1, confer greater metabolic resistance, and in the case of the 4-(4-cyanotetrahydro-2H-pyranyl) compounds, substantially reduce lipophilicity. One derivative, 1-(2-bromophenyl)-N-(1-cyanocyclohexyl)-5-(4-methoxyphenyl)-4-methylpyrazole-3-carboxamide (9n), showed high affinity (K(i) = 15.7 nM) and selectivity for binding to CB(1) receptors. The corresponding 4-(4-cyanotetrahydro-2H-pyranyl) derivative (9m) also showed quite high affinity for CB(1) receptors (K(i) = 62 nM) but was found to have even higher affinity (K(i) = 29 nM) for the structurally unrelated 18 kDa translocator protein (TSPO). Some other minor structural changes among 9a-s were also found to switch binding selectivity from CB(1) receptors to TSPO or vice versa. These unexpected findings and their implications for the development of selective ligands or PET radioligands for CB(1) receptors or TSPO are discussed in relation to current pharmacophore models of CB(1) receptor and TSPO binding sites.

  DOI：

  10.1021/jm2000536
• 作为产物：
  描述：

  邻氯苯胺 、 2-氯乙酰乙酸乙酯 在 盐酸 、 sodium nitrite 、 sodium acetate 作用下， 以 乙醇 、 水 为溶剂， 反应 0.5h， 以79.8%的产率得到C-ethoxycarbonyl-N-(2-chlorophenyl)hydrazonoyl chloride
  参考文献：
  名称：

  包含1,2,4-三唑酮部分作为c-Met激酶抑制剂的新型4-苯氧基喹啉衍生物的设计，合成及构效关系

  摘要：

  合成了一系列含有1,2,4-三唑酮部分的新型4-苯氧基喹啉衍生物，并评估了它们对四种癌细胞系（HT-29，H460，A549和MKN-45）的体外细胞毒活性。大多数化合物表现出中度至显着的细胞毒性。化合物33，37，39，44，46，47，53，55，61，64和66进行了进一步考察了它们的抑制活性对c-Met激酶。最有前途的化合物47（c-Met IC 50值为1.57 nM）对HT-29，H460，A549和MKN-45细胞系表现出显着的细胞毒性，IC 50值分别为0.08μM，0.14μM，0.11μM和0.031μM，因此是1.1- 2.3-倍于福瑞替尼。他们的初步结构-活性关系（SAR）研究表明，末端苯环上的吸电子基团有助于改善抗肿瘤活性。

  DOI：

  10.1016/j.ejmech.2016.07.059

文献信息

• Lipoxygenase-Inhibitoren, 4. Mitt.: Synthese und Cyclisierungsreaktionen offenkettigerN1-arylsubstituierter Amidrazone
  作者：Petra Frohberg、Cornelia Kupfer、Peter Stenger、Ute Baumeister、Peter Nuhn

  DOI：10.1002/ardp.19953280607

  日期：——

  Ausgehend von α‐Carbonylcarbonsäurearylhydrazonochloriden, die durch Japp‐Klingemann‐Spaltung erhalten werden, werden α‐Carbonylcarbonsäurearylhydrazonoamide,‐ester sowie ‐thioester synthetisiert, deren inhibitorische Wirkung gegenüber 15‐ bzw. 5‐Lipoxygenase beschrieben wird. Umsetzungen der Amidrazonderivate mit Formaldehyd führen zu Triazol‐,Triazolin‐ und in unerwarteter Weise zu Benzotriazepinderivaten

  从通过 Japp-Klingemann 裂解获得的 α-羰基羧基酰肼基氯化物开始，合成了 α-羰基羧基酰肼基酰胺、酯和硫酯，描述了它们对 15- 和 5- 脂氧合酶的抑制作用。脒腙衍生物与甲醛反应生成三唑、三唑啉，并且出人意料地生成苯并三氮杂衍生物。
• Synthesis of 1,2,4-Triazol-3-imines via Selective Stepwise Cycloaddition of Nitrile Imines with Organo-cyanamides
  作者：Pallavi Sharma、Shreesha V. Bhat、M. R. Ranga Prabhath、Andrew Molino、Elisa Nauha、David J. D. Wilson、John E. Moses

  DOI：10.1021/acs.orglett.8b01673

  日期：2018.7.20

  A convenient method for the synthesis of 1,2,4-triazol-3-imines through a selective, formal, 1,3-dipolar cycloaddition of organo-cyanamide ions with nitrile imine dipoles is reported. Hydrolysis of the 1,2,4-triazol-3-imines yields the corresponding 1,2,4-triazol-5-ones. A stepwise mechanism, supported by DFT calculations, is invoked to explain the reaction selectivity.

  报道了一种通过有机腈酰胺离子与腈亚胺偶极的选择性，形式，1,3-偶极环加成反应合成1,2,4-三唑-3-亚胺的简便方法。1,2,4-三唑-3-亚胺的水解产生相应的1,2,4-三唑-5-酮。调用DFT计算支持的逐步机制来解释反应的选择性。
• SUBSTITUTED N-(4-CYANO-1H-PYRAZOL-3-YL)METHYLAMINE DERIVATIVES, PREPARATION THEREOF AND THERAPEUTIC USE THEREOF
  申请人：BARTH Francis

  公开号：US20100041709A1

  公开（公告）日：2010-02-18

  The present invention relates to compounds corresponding to formula (I): Wherein X, R 1 , R 2 , R 3 and R 4 are as defined herein. The invention further relates to preparation and therapeutic use of these compounds.

  本发明涉及与以下化学式（I）对应的化合物：其中X、R1、R2、R3和R4如本文所定义。该发明还涉及这些化合物的制备和治疗用途。
• Design, synthesis, and photophysics of bi- and tricyclic fused pyrazolines
  作者：Alexandra V. Popova、Ali Kanaa、Vladislava S. Vavilova、Maria A. Mironova、Pavel A. Slepukhin、Enrico Benassi、Nataliya P. Belskaya

  DOI：10.1039/d0nj06287a

  日期：——

  Three series of bi- and tricyclic functionalized new pyrazoline fluorophores have been synthesized for investigation of their photophysical properties. Spectral studies indicated significant absorption and emission properties. The quantum yields reached 93% and Stokes shifts increased up to 148 nm. The compounds exhibited positive solvato(fluoro)chromism. Fluorescence was sensitive to both structural

  合成了三个系列的双环和三环功能化的新型吡唑啉荧光团，以研究其光物理性质。光谱研究表明明显的吸收和发射性质。量子产率达到93％，斯托克斯位移增加到148 nm。该化合物表现出正溶剂化（氟）色度。荧光对结构变化和微环境都敏感，特别是对质子溶剂，如EtOH，n -BuOH和DMSO / H 2敏感O的混合物，与乙二醇。实验结果得到了量子力学计算的支持。取代基的电子性质及其空间效应的修饰可以改变分子内电荷转移（ICT）的性质和方向。这些发现为开发具有可调光物理性质的新型稠合吡唑啉提供了宝贵的见识。吡唑啉表现出高强度的固态发射，使其适合用于光子学。活性官能团可用于结合吡唑啉和天然化合物，药物和诊断分子，以用于生物系统和药物中。
• Functionalized pyrazoles and pyrazolo[3,4-d]pyridazinones: Synthesis and evaluation of their phosphodiesterase 4 inhibitory activity
  作者：Pierfrancesco Biagini、Claudio Biancalani、Alessia Graziano、Nicoletta Cesari、Maria Paola Giovannoni、Agostino Cilibrizzi、Vittorio Dal Piaz、Claudia Vergelli、Letizia Crocetti、Maurizio Delcanale、Elisabetta Armani、Andrea Rizzi、Paola Puccini、Paola Maria Gallo、Daniele Spinabelli、Paola Caruso

  DOI：10.1016/j.bmc.2010.03.066

  日期：2010.5

  A series of pyrazoles and pyrazolo[3,4-d]pyridazinones were synthesized and evaluated for their PDE4 inhibitory activity. All the pyrazoles were found devoid of activity, whereas some of the novel pyrazolo[3,4-d]pyridazinones showed good activity as PDE4 inhibitors. The most potent compounds in this series showed an IC50 in the nanomolar range. The ability to inhibit TNF-alpha release in human PBMCs was determined for two representative compounds, finding values in the sub-micromolar range. SARs studies demonstrated that the best arranged groups around the heterocyclic core are 2-chloro-, 2-methyl- and 3-nitrophenyl at position 2, an ethyl ester at position 4 and a small alkyl group at position 6. Molecular modeling studies performed on a representative compound allowed to define its binding mode to the PDE4B isoform. (C) 2010 Elsevier Ltd. All rights reserved.