4-(3,4-Dichloroanilino)-4-oxobut-2-enoic acid | 54012-56-5

• 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: 4-(3,4-Dichloroanilino)-4-oxobut-2-enoic acid
• CAS: 54012-56-5
• 化学式: C₁₀H₇Cl₂NO₃
• mdl: MFCD00756719
• 分子量: 260.076
• InChiKey: YMYKNYVBUCMJOG-UHFFFAOYSA-N

物化性质

• 熔点：
  205°C

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 危险类别码：
  R36/37/38
• 海关编码：
  2924299090
• 安全说明：
  S26,S36/37/39

反应信息

• 作为反应物：
  描述：

  4-(3,4-Dichloroanilino)-4-oxobut-2-enoic acid 在 吡啶 、 氯化亚砜 、 sodium acetate 作用下， 以 乙酸酐 为溶剂， 反应 1.75h， 生成 3,4-二氯-1-(3,4-二氯苯基)吡咯-2,5-二酮
  参考文献：
  名称：

  An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity

  摘要：

  Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.

  DOI：

  10.1021/jm301565b
• 作为产物：
  描述：

  马来酸酐 、 3,4-二氯苯胺 以 1,4-二氧六环 为溶剂， 反应 6.0h， 生成 4-(3,4-Dichloroanilino)-4-oxobut-2-enoic acid
  参考文献：
  名称：

  通过基于异羟肟酸的LasB抑制剂处理铜绿假单胞菌的毒力

  摘要：

  为了寻找新的抗生素来对抗耐药性病原体的挑战性传播，细菌蛋白酶代表了致病阻断剂发展的有希望的目标。蛋白酶抑制剂的常见基序是异羟肟酸功能，然而该组常常与各种金属蛋白酶的非特异性抑制有关。在这项工作中，抑制铜绿假单胞菌分泌的有害锌金属蛋白酶LasB通过异羟肟酸酯衍生物进行了描述。本抑制剂是基于最近报道的高选择性硫醇骨架而开发的。使用X射线晶体学，缺乏对一系列人类基质金属蛋白酶的抑制作用可归因于保留S1'口袋的独特结合模式。该抑制剂被证明可以恢复抗菌肽LL-37的作用，减少铜绿假单胞菌生物膜的形成，并且对于LasB抑制剂而言，这是首次减少细胞外DNA的释放。因此，它能够破坏几种重要的细菌抗性机制。这些结果突出了蛋白酶抑制剂对抗细菌感染的潜力，并指出了即使使用强锌锚定剂也可以实现选择性抑制的可能性。

  DOI：

  10.1021/acschembio.8b00257

文献信息

• Potent Nematicidal Activity of Maleimide Derivatives on <i>Meloidogyne incognita</i>
  作者：Kodjo Eloh、Monica Demurtas、Manuel Giacomo Mura、Alessandro Deplano、Valentina Onnis、Nicola Sasanelli、Andrea Maxia、Pierluigi Caboni

  DOI：10.1021/acs.jafc.6b02250

  日期：2016.6.22

  Different maleimide derivatives were synthesized and assayed for their in vitro activity on the soil inhabiting, plant-parasitic nematode Meloidogyne incognita, also known as root-knot nematode. The compounds maleimide, N-ethylmaleimide, N-isopropylmaleimide, and N-isobutylmaleimide showed the strongest nematicidal activity on the second stage juveniles of the root-knot nematode with EC50/72h values of 2.6 +/- 1.3, 5.1 +/- 3.4, 16.2 +/- 5.4, and 19.0 +/- 9.0 mg/L, respectively. We also determined the nematicidal activity of copper sulfate, finding an EC50 value of 48.6 +/- 29.8 mg/L. When maleimide at 1 mg/L was tested in combination with copper sulfate at SO mg/L, we observed 100% mortality of the nematodes. We performed a GC-MS metabolomics analysis after treating nematodes with maleimide at 8 mg/L for 24 h. This analysis revealed altered fatty acids and diglyceride metabolites such as oleic acid, palmitic acid, and 1-monopalmitin. Our results suggest that maleimide may be used as a new interesting building block for developing new nematicides in combination with copper salts.
• [EN] GHRELIN RECEPTOR MODULATORS<br/>[FR] MODULATEURS DU RÉCEPTEUR DE LA GHRÉLINE
  申请人：7TM PHARMA AS

  公开号：WO2008092681A1

  公开（公告）日：2008-08-07

  [EN] Compounds of Formula (IA) or (IB) modulate ghrelin receptor activity, and are useful in the treatment of, for example, obesity and eating disorders: wherein W is, in either orientation, -C(=O)N(R₃)-, or -C(=O)O-; R is hydrogen or C₁-C₄ alkyl; R₁ is selected from hydrogen, (C₁-C₄)alkyl, cycloalkyl, fully or partially fluorinated (C₁-C₄)alkyl, or -OR₁₀; and R₂ is selected from (i) hydrogen and (ii) (C₁-C₄)alkyl, cycloalkyl, cycloalkenyl, and non aromatic heterocyclyl, each optionally substituted by -F, -CN, C₁-C₄ alkyl, cyclopropyl, -NR₇COR₀, -NR₇SO₂R₀, -COR₀, -COOH, -SOR₉, -SO₂R₀, -OR₁₀, -NR₇R₈, or -NR₇COOR₈; and (iii) aryl, aryl-(C₁-C₂)alkyl-, heteroaryl and heteroaryl-(C₁-C₂ alkyl)- each optionally substituted in the ring part or R₁ and R₂, together with the nitrogen to which they are attached, form an optionally substituted cyclic amino group; R₃ is selected from hydrogen, (C₁-C₄)alkyl, cycloalkyl, fully or partially fluorinated (C₁-C₄)aIkyl, or -OR₁₀; and R₄ is selected from (iv) hydrogen and (v) (C₁-C₄)alkyl, cycloalkyl, and non aromatic heterocyclyl, each optionally substituted by -F, -CN, -NR₇COR₀, -NR₇SO₂R₀, -COR₀, - COOH, -SOR₉, -SO₂R₀, -OR₁₀, -NR₇R₈, or -NR₇COOR₈; and (vi) aryl, aryl-(C₁-C₂)alkyl-, heteroaryl and heteroaryl-(C₁-C₂ alkyl)- each optionally substituted in the ring part thereof; or R₃ and R₄, together with the nitrogen to which they are attached, form an optionally substituted cyclic amino group; L is a linker radical of formula -(CR₁₁R₁₃)_aB(CR₁₂R₁₄)b- as defined in the specification; R₀, R₇, R₈, R₉ and R₁₀ are as defined in the specification.
  [FR] Les composés de formule (IA) ou (IB) modulent l'activité du récepteur de la ghréline et sont utiles dans le traitement, par exemple, de l'obésité et des troubles de l'alimentation : où W représente, dans l'une ou l'autre orientation, -C(=O)N(R₃)- ou -C(=O)O-; R représente un atome d'hydrogène ou un groupe alkyle en C₁ à C₄; R₁ est choisi parmi un atome d'hydrogène, un groupe alkyle (en C₁ à C₄), cycloalkyle, un groupe alkyle (en C₁ à C₄) totalement ou partiellement fluoré ou -OR₁₀; et R₂ est choisi parmi (i) un atome d'hydrogène et (ii) un groupe alkyle (en C₁ à C₄), cycloalkyle, cycloalcényle et hétérocyclyle non aromatique, chacun éventuellement substitué par -F, -CN, un groupe alkyle en C₁ à C₄, cyclopropyle, -NR₇COR₀, -NR₇SO₂R₀, -COR₀, -COOH, -SOR₉, -SO₂R₀, -OR₁₀, -NR₇R₈ ou -NR₇COOR₈; et (iii) un groupe aryle, aryl-alkyl (en C₁ à C₂)-, hétéroaryle et hétéroaryl-alkyl (en C₁ à C₂)- chacun éventuellement substitué dans la partie cyclique ou R₁ et R₂, conjointement avec l'atome d'azote auquel ils sont fixés, forment un groupe amino cyclique éventuellement substitué; R₃ est choisi parmi un atome d'hydrogène, un groupe alkyle (en C₁ à C₄), cycloalkyle, alkyle (en C₁ à C₄) totalement ou partiellement fluoré ou -OR₁₀; et R₄ est choisi parmi (iv) un atome d'hydrogène et (v) un groupe alkyle (en C₁ à C₄), cycloalkyle hétérocyclyle non aromatique, chacun éventuellement substitué par -F, -CN, -NR₇COR₀, -NR₇SO₂R₀, -COR₀, -COOH, -SOR₉, -SO₂R₀, -OR₁₀, -NR₇R₈, ou -NR₇COOR₈; et (vi) un groupe aryle, aryl-alkyl (en C₁ à C₂)-, hétéroaryle et hétéroaryl-(alkyl en C₁ à C₂)- chacun éventuellement substitué dans sa partie cyclique; ou R₃ et R₄, conjointement avec l'atome d'azote auquel ils sont fixés, forment une groupe amino cyclique éventuellement substitué; L représente un radical lieur de formule -(CR₁₁R₁₃)_aB(CR₁₂R₁₄)b- telle que définie dans le mémoire; R₀, R₇, R₈, R₉ et R₁₀ sont tels que définis dans le mémoire.
• An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity
  作者：Brian Budke、Jay H. Kalin、Michal Pawlowski、Anna S. Zelivianskaia、Megan Wu、Alan P. Kozikowski、Philip P. Connell

  DOI：10.1021/jm301565b

  日期：2013.1.10

  Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.
• Tackling <i>Pseudomonas aeruginosa</i> Virulence by a Hydroxamic Acid-Based LasB Inhibitor
  作者：Andreas M. Kany、Asfandyar Sikandar、Samir Yahiaoui、Jörg Haupenthal、Isabell Walter、Martin Empting、Jesko Köhnke、Rolf W. Hartmann

  DOI：10.1021/acschembio.8b00257

  日期：2018.9.21

  highly selective thiol scaffold. Using X-ray crystallography, the lack of inhibition of a range of human matrix metalloproteases could be attributed to a distinct binding mode sparing the S1′ pocket. The inhibitor was shown to restore the effect of the antimicrobial peptide LL-37, decrease the formation of P. aeruginosa biofilm and, for the first time for a LasB inhibitor, reduce the release of extracellular

  为了寻找新的抗生素来对抗耐药性病原体的挑战性传播，细菌蛋白酶代表了致病阻断剂发展的有希望的目标。蛋白酶抑制剂的常见基序是异羟肟酸功能，然而该组常常与各种金属蛋白酶的非特异性抑制有关。在这项工作中，抑制铜绿假单胞菌分泌的有害锌金属蛋白酶LasB通过异羟肟酸酯衍生物进行了描述。本抑制剂是基于最近报道的高选择性硫醇骨架而开发的。使用X射线晶体学，缺乏对一系列人类基质金属蛋白酶的抑制作用可归因于保留S1'口袋的独特结合模式。该抑制剂被证明可以恢复抗菌肽LL-37的作用，减少铜绿假单胞菌生物膜的形成，并且对于LasB抑制剂而言，这是首次减少细胞外DNA的释放。因此，它能够破坏几种重要的细菌抗性机制。这些结果突出了蛋白酶抑制剂对抗细菌感染的潜力，并指出了即使使用强锌锚定剂也可以实现选择性抑制的可能性。