methyl (E)-3-(2-amino-4-chlorophenyl)acrylate | 150869-42-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: methyl (E)-3-(2-amino-4-chlorophenyl)acrylate
• 英文别名: methyl trans-4-chloro-2-aminocinnamate；(E)-3-(2-Amino-4-chlorophenyl)-2-propenoic acid methyl ester；methyl (E)-3-(2-amino-4-chlorophenyl)prop-2-enoate
• CAS: 150869-42-4
• 化学式: C₁₀H₁₀ClNO₂
• 分子量: 211.648
• InChiKey: VHCSJCFEYXNKHF-HWKANZROSA-N

物化性质

• 沸点：
  360.1±32.0 °C(Predicted)
• 密度：
  1.285±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (E)-3-(2-amino-4-chlorophenyl)acrylate 在 吡啶 、 苯磺酰氯 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 以40 g (76%)的产率得到methyl trans-4-chloro-2-[(phenylsulfonyl)amino]cinnamate
  参考文献：
  名称：

  Bicycliccarbonyl indole compounds as anti-inflammatory/analgesic agents

  摘要：

  该发明提供了以下公式的化合物：或其药学上可接受的盐，其中A是C1-6烷基或—NR1—；Z是C(═L)R2，或SO2R3；U是CH或N；W和Y分别选择自—CH2—，O，S和—N—R1；m为1、2或3；q和r独立地为0、1或2；X独立地选择自卤素，C1-4烷基，卤代C1-4烷基，羟基，C1-4烷氧基，卤代C1-4烷氧基或类似物；n为1或2；L为氧或硫；R1为氢或C1-4烷基；R2为羟基，C1-6烷基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基，C3-7环烷氧基，C1-4烷基(C3-7环烷氧基)，—NR4R5或类似物；R3为C1-6烷基或卤代C1-6烷基；R4和R5独立地选择自氢，C1-6烷基和卤代C1-6烷基。该发明还提供了一种药物组合物，用于治疗前列腺素作为病原体参与的医疗状况。

  公开号：

  US06303628B1
• 作为产物：
  描述：

  3-氯苯胺 在 palladium on activated charcoal N-碘代丁二酰亚胺 、 potassium carbonate 、 溶剂黄146 作用下， 以 乙二醇二甲醚 为溶剂， 反应 48.0h， 生成 methyl (E)-3-(2-amino-4-chlorophenyl)acrylate
  参考文献：
  名称：

  Bioisosteric Modifications of 2-Arylureidobenzoic Acids:  Selective Noncompetitive Antagonists for the Homomeric Kainate Receptor Subtype GluR5

  摘要：

  2-Arylureidobenzoic acids (AUBAs) have recently been presented as the first series of selective noncompetitive GluR5 antagonists. In this paper we have modified the acidic moiety of the AUBAs by introducing different acidic and neutral groups, and similarly, we have replaced the urea linker of the AUBAs with other structurally related linkers. Replacing the acid with neutral substituents led to inactive compounds in all instances, showing that an acidic moiety is necessary for activity. Replacing the carboxylic moiety in 2a with a sulfonic acid (5c) or a tetrazole ring (5d) improved the potency at GluR5 receptors (compounds 5c and 5d showed IC50 values of 1.5 and 2.0 muM, respectively, compared to compound 2a with IC50 = 4.8 muM). Compound 5c did not show improved in vivo activity in the ATPA rigidity test compared to 2a, whereas compound 5d was 4 times more potent than 2a. All compounds wherein the urea linker had been replaced showed lower or no activity. The results described extend the knowledge of structure-activity relationships for the AUBAs, and compound 5d may prove to be a good candidate for studying GluR5 receptors in vitro and in vivo.

  DOI：

  10.1021/jm030638w

文献信息

• 4-Substituted-3-phenylquinolin-2(1<i>H</i>)-ones:  Acidic and Nonacidic Glycine Site <i>N</i>-Methyl-<scp>d</scp>-aspartate Antagonists with <i>in</i> <i>Vivo</i> Activity
  作者：Robert W. Carling、Paul D. Leeson、Kevin W. Moore、Christopher R. Moyes、Matthew Duncton、Martin L. Hudson、Raymond Baker、Alan C. Foster、Sarah Grimwood、John A. Kemp、George R. Marshall、Mark D. Tricklebank、Kay L. Saywell

  DOI：10.1021/jm9605492

  日期：1997.2.1

  4-Substituted-3-phenylquinolin-2(1H)-ones have been synthesized and evaluated in vitro for antagonist activity at the glycine site on the NMDA (N-methyl-D-aspartate) receptor and in vivo for anticonvulsant activity in the DBA/2 strain of mouse in an audiogenic seizure model. 4-Amino-3-phenylquinolin-2(1H)-one (3) is 40-fold lower in binding affinity but only 4-fold weaker as an anticonvulsant than

  合成了4-取代的3-苯基喹啉-2（1H）-ones，并在体外评估了NMDA（N-甲基-D-天冬氨酸）受体甘氨酸位点的拮抗剂活性，并在体内评估了DBA中的抗惊厥活性。在音源性癫痫发作模型中为小鼠的/ 2品系。4-氨基-3-苯基喹啉-2（1H）-一（3）的结合亲和力比酸性4-羟基化合物1低40倍，但作为抗惊厥剂仅弱4倍。图3给出了一种酸性化合物（6，pKa ＝ 6.0），其亲和力被完全恢复，但体内效力却显着降低（表1）。1的4位甲基化可得到18个结果，从而消除了可测量的亲和力，但是，中性氢键接受基团与18的甲基相连会产生具有与1相当的体外和体内活性的化合物（例如，表2中的23和28）。用乙基取代1的4-羟基可消除活性（42），但再次，将中性氢键受体结合到末端碳原子上可恢复亲和力（例如，表3中的36、39和40）。用氨基取代高亲和力化合物2的4-羟基会产生亲和力降低200倍的化合物（43； IC50
• Visible‐Light‐Driven Isocyanide Insertion to <i>o</i> ‐Alkenylanilines: A Route to Isoindolinone Synthesis
  作者：Anjali Dahiya、Bubul Das、Ashish Kumar Sahoo、Bhisma K. Patel

  DOI：10.1002/adsc.202101431

  日期：2022.3

  intermolecular radical insertion of isocyanides to electron-deficient o-alkenylanilines leading to isoindolinone is reported. Deuterium (D2O) and H2O18 labelling experiments suggest H and O incorporation in the product. The formation of an N-centered radical (NCR) via stepwise PT/ET process was confirmed by radical trapping experiments, photoluminescence, cyclic voltammetry and DFT studies. This photo cascade methodology

  报道了可见光介导的异氰化物分子间自由基插入到缺电子的o-烯基苯胺，导致异吲哚啉酮。氘 (D 2 O) 和 H 2 O 18标记实验表明产品中含有 H 和 O。通过自由基捕获实验、光致发光、循环伏安法和 DFT 研究证实了通过逐步 PT/ET 过程形成N中心自由基 (NCR) 。这种光级联方法总体上是一种氧化还原中性工艺，具有无金属条件和广泛的基材范围（32 个示例）。GABA 受体拮抗剂类似物的合成显示了该方法的实用性。
• Stereoselective construction of deoxy-cruciferane alkaloids by NHC-catalyzed intramolecular annulation of homoenolate with quinazolinone
  作者：Milind M. Ahire、Mahesh D. Pol、Dattatry S. Kavale、Rajesh G. Gonnade、Santosh B. Mhaske

  DOI：10.1039/c9ob01243e

  日期：——

  Chiral N-heterocyclic carbene (NHC)-catalyzed intramolecular [3 + 2] annulation of enals with an unactivated imine moiety of quinazolinone via formal homoenolate cycloaddition has been demonstrated. It is an excellent approach for stereoselective syntheses of deoxy-cruciferane alkaloids comprising a biologically important pyrroloindoline scaffold. Notably, this is the first report on the NHC-catalyzed

  已证明手性N杂环卡宾（NHC）催化的分子内[3 + 2]通过正式的均烯酸酯环加成反应环化带有喹唑啉酮的亚胺部分的烯醛。对于包含生物学上重要的吡咯并二氢吲哚骨架的脱氧-十字花青烷生物碱的立体选择性合成而言，这是一种极好的方法。值得注意的是，这是有关NHC催化的不对称分子内同戊烯酸酯与环状N-酰基am环合的首次报道。
• Bicycliccarbonyl indole compounds as anti-inflammatory/analgesic agents
  申请人：Pfizer Inc

  公开号：US06303628B1

  公开（公告）日：2001-10-16

  This invention provides a compound of the following formula: or the pharmaceutically acceptable salts thereof wherein A is C 1-6 alkylene or —NR1—; Z is C(═L)R2, or SO2R3; U is CH or N; W and Y are independently selected from —CH2—, O, S and —N—R1; m is 1, 2 or 3; q and r are independently 0, 1 or 2; X is independently selected from halogen, C1-4 alkyl, halo-substituted C1-4 alkyl, hydroxy, C1-4 alkoxy, halo-substituted C1-4 alkoxy or the like; n is 1 or 2; L is oxygen or sulfur; R1 is hydrogen or C1-4 alkyl; R2 is hydroxy, C1-6alkyl, halo-substituted C1-6 alkyl, C1-6 alkoxy, halo-substituted C1-6 alkoxy, C3-7 cycloalkoxy, C1-4 alkyl(C3-7 cycloalkoxy), —NR4R5 or the like; R3 is C1-6 alkyl or halo-substituted C1-6 alkyl; and R4 and R5 are independently selected from hydrogen, C1-6 alkyl and halo-substituted C1-6alkyl. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens.

  该发明提供了以下公式的化合物：或其药学上可接受的盐，其中A是C1-6烷基或—NR1—；Z是C(═L)R2，或SO2R3；U是CH或N；W和Y分别选择自—CH2—，O，S和—N—R1；m为1、2或3；q和r独立地为0、1或2；X独立地选择自卤素，C1-4烷基，卤代C1-4烷基，羟基，C1-4烷氧基，卤代C1-4烷氧基或类似物；n为1或2；L为氧或硫；R1为氢或C1-4烷基；R2为羟基，C1-6烷基，卤代C1-6烷基，C1-6烷氧基，卤代C1-6烷氧基，C3-7环烷氧基，C1-4烷基(C3-7环烷氧基)，—NR4R5或类似物；R3为C1-6烷基或卤代C1-6烷基；R4和R5独立地选择自氢，C1-6烷基和卤代C1-6烷基。该发明还提供了一种药物组合物，用于治疗前列腺素作为病原体参与的医疗状况。
• A Highly Efficient Copper(I)-Catalyzed Cascade Reaction of<i>o</i>-Alkenylphenyl Isothiocyanates with Isocyanides Leading to 5<i>H</i>-Benzo[<i>d</i>]imidazo[5,1-<i>b</i>][1,3]thiazines
  作者：Wenyan Hao、Jian Huang、Shanshan Jie、Mingzhong Cai

  DOI：10.1002/ejoc.201500800

  日期：2015.10

  The highly efficient copper(I)-catalyzed cascade reaction of (E)-3-(2-isothiocyanatophenyl)acrylates and (E)-3-(2-isothiocyanatophenyl)acrylonitriles with isocyanides was explored. The method provides an expedient route for the synthesis of 5H-benzo[d]imidazo[5,1-b][1,3]thiazines in good to excellent yields by using CuCl (10 mol-%) as the catalyst and K3PO4 (2.0 equiv.) as the base in THF at 70 °C

  探索了高效铜 (I) 催化的 (E)-3-(2-异硫氰酸根合苯基) 丙烯酸酯和 (E)-3-(2-异硫氰酸根合苯基) 丙烯腈与异氰化物的级联反应。该方法为以 CuCl (10 mol-%) 为催化剂和 K3PO4 合成 5H-苯并[d]咪唑并[5,1-b][1,3]噻嗪类化合物提供了一条便利的途径，收率良好至极好2.0 当量）作为 70 °C 下 THF 中的碱。该反应涉及 [3+2] 环加成和随后的分子内 C-S 键形成。