4-[(4-cyanophenyl)amino]-4-oxobutanoic acid

• 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-[(4-cyanophenyl)amino]-4-oxobutanoic acid
• 英文别名: 4-(4-cyanophenylamino)-4-oxobutanoic acid；N-(4-cyano-phenyl)-succinamic acid；N-(4-Cyan-phenyl)-succinamidsaeure；Bernsteinsaeure-mono-(4-cyan-anilid)；4-Cyan-succinanilsaeure；4-(4-Cyanoanilino)-4-oxobutanoic acid
• 化学式: C₁₁H₁₀N₂O₃
• mdl: MFCD00566771
• 分子量: 218.212
• InChiKey: PVXNEGDGLGDODH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-氨基-9-乙基咔唑 、 4-[(4-cyanophenyl)amino]-4-oxobutanoic acid 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以71%的产率得到N-(4-cyanophenyl)-N'-(9-ethyl-9H-carbazol-3-yl)butanediamide
  参考文献：
  名称：

  Identification of novel quinazolinedione derivatives as RORγt inverse agonist

  摘要：

  Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was also optimized; a quinazolinedione derivative 18i suppressed the increase of IL-17A mRNA level in the lymph node of a rat model of experimental autoimmune encephalomyelitis (EAE) upon oral administration. These results indicate that the novel quinazolinedione derivatives have great potential as orally available small-molecule ROR gamma t inverse agonists for the treatment of Th17-driven autoimmune diseases. A U-shaped bioactive conformation of this chemotype with ROR gamma t protein was also observed. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.12.039
• 作为产物：
  描述：

  丁二酸酐 、 对氨基苯腈 以 氯仿 为溶剂， 反应 16.0h， 以76%的产率得到4-[(4-cyanophenyl)amino]-4-oxobutanoic acid
  参考文献：
  名称：

  新型N 6取代腺苷-5′- N-甲基羧酰胺作为A 3腺苷受体激动剂的合成与评价

  摘要：

  合成了许多N 6-取代的腺苷-5'- N-甲基羧酰胺，并就其受体亲和力，选择性和心脏保护作用探讨了其药理作用。第一系列的化合物，4A - 4F和5A - 5F显示出适度的受体的亲和力的A 3 AR与ķ我在低位μM中间范围的值。但是，在N 6位（在化合物4g和5g中）引入4-（2-氨基乙基）-2,6-二叔丁基苯酚基团可以显着改善与K i值分别为30和9 nM。当引入功能化的接头时，亲和力和选择性都得到了改善。所述Ñ 6 -苯基系列，化合物7A - 7D，表明低到中纳摩尔亲和力受体（ķ我 = 2.3-45.0纳米），与图7B显示用于A 109倍的选择性3 AR（Vs的1）。所述Ñ 6 -苄基系列图9a - 9c中也被证明是有效的和选择性阿3 AR激动剂和较长链长的接头13在A是不能容忍的3 AR，无需取消亲和力或选择性。通过模拟的局部缺血细胞培养测定法证明了心脏保护作用，其中7b，7c，9a，9b和9c均在100

  DOI：

  10.1016/j.bmc.2010.03.047

文献信息

• Synthesis and evaluation of new N6-substituted adenosine-5′-N-methylcarboxamides as A3 adenosine receptor agonists
  作者：Shane M. Devine、Alison Gregg、Heidi Figler、Kate McIntosh、Vijay Urmaliya、Joel Linden、Colin W. Pouton、Paul J. White、Steven E. Bottle、Peter J. Scammells

  DOI：10.1016/j.bmc.2010.03.047

  日期：2010.5

  A number of N6-substituted adenosine-5′-N-methylcarboxamides were synthesised and their pharmacology, in terms of their receptor affinity, selectivity and cardioprotective effects, were explored. The first series of compounds, 4a–4f and 5a–5f, showed modest receptor affinity for the A3AR with Ki values in the low to mid μM range. However, the incorporation of a 4-(2-aminoethyl)-2,6-di-tert-butylphenol

  合成了许多N 6-取代的腺苷-5'- N-甲基羧酰胺，并就其受体亲和力，选择性和心脏保护作用探讨了其药理作用。第一系列的化合物，4A - 4F和5A - 5F显示出适度的受体的亲和力的A 3 AR与ķ我在低位μM中间范围的值。但是，在N 6位（在化合物4g和5g中）引入4-（2-氨基乙基）-2,6-二叔丁基苯酚基团可以显着改善与K i值分别为30和9 nM。当引入功能化的接头时，亲和力和选择性都得到了改善。所述Ñ 6 -苯基系列，化合物7A - 7D，表明低到中纳摩尔亲和力受体（ķ我 = 2.3-45.0纳米），与图7B显示用于A 109倍的选择性3 AR（Vs的1）。所述Ñ 6 -苄基系列图9a - 9c中也被证明是有效的和选择性阿3 AR激动剂和较长链长的接头13在A是不能容忍的3 AR，无需取消亲和力或选择性。通过模拟的局部缺血细胞培养测定法证明了心脏保护作用，其中7b，7c，9a，9b和9c均在100
• Photocatalytic coupling of electron-deficient alkenes using oxalic acid as a traceless linchpin
  作者：Zugen Wu、Mingyue Wu、Kun Zhu、Jie Wu、Yixin Lu

  DOI：10.1016/j.chempr.2022.12.013

  日期：2023.1

  Reductive alkene cross-coupling represents a straightforward strategy for the construction of C–C bonds from readily available alkene feedstocks. A one-pot protocol, utilizing oxalic acid as a traceless linchpin, has been developed to achieve direct cross-coupling of electron-deficient alkenes. The overall process is a two-step transformation involving hydrocarboxylation followed by decarboxylative

  还原性烯烃交叉偶联代表了从现成的烯烃原料构建 C-C 键的直接策略。已经开发出一种利用草酸作为无痕关键的一锅法来实现缺电子烯烃的直接交叉偶联。整个过程是一个两步转化，涉及加氢羧化，然后是脱羧交叉偶联。双光催化剂系统对于成功至关重要，并协同促进两个反应步骤。该反应支持生物活性分子的有效合成。光氧化还原催化为 CO 2的生成提供了一种简单而温和的途径从草酸中分离出自由基阴离子，这为这种活性中间体在精细化学品合成中的广泛应用铺平了道路。
• Bogert; Wise, Journal of the American Chemical Society, 1912, vol. 34, p. 701
  作者：Bogert、Wise

  DOI：——

  日期：——
• Identification of novel quinazolinedione derivatives as RORγt inverse agonist
  作者：Yoshiyuki Fukase、Ayumu Sato、Yoshihide Tomata、Atsuko Ochida、Mitsunori Kono、Kazuko Yonemori、Keiko Koga、Toshitake Okui、Masashi Yamasaki、Yasushi Fujitani、Hideyuki Nakagawa、Ryoukichi Koyama、Masaharu Nakayama、Robert Skene、Bi-Ching Sang、Isaac Hoffman、Junya Shirai、Satoshi Yamamoto

  DOI：10.1016/j.bmc.2017.12.039

  日期：2018.2

  Novel small molecules were synthesized and evaluated as retinoic acid receptor-related orphan receptor-gamma t (ROR gamma t) inverse agonists for the treatment of inflammatory and autoimmune diseases. A hit compound, 1, was discovered by high-throughput screening of our compound library. The structure-activity relationship (SAR) study of compound 1 showed that the introduction of a chlorine group at the 3-position of 4-cyanophenyl moiety increased the potency and a 3-methylpentane-1,5-diamide linker is favorable for the activity. The carbazole moiety of 1 was also optimized; a quinazolinedione derivative 18i suppressed the increase of IL-17A mRNA level in the lymph node of a rat model of experimental autoimmune encephalomyelitis (EAE) upon oral administration. These results indicate that the novel quinazolinedione derivatives have great potential as orally available small-molecule ROR gamma t inverse agonists for the treatment of Th17-driven autoimmune diseases. A U-shaped bioactive conformation of this chemotype with ROR gamma t protein was also observed. (C) 2017 Elsevier Ltd. All rights reserved.