ethyl 1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate | 259654-81-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: ethyl 1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate
• 英文别名: ethyl 1-(4-chlorophenyl)-2,5-dimethylpyrrole-3-carboxylate
• CAS: 259654-81-4
• 化学式: C₁₅H₁₆ClNO₂
• 分子量: 277.751
• InChiKey: WGWQKBOKWUZMSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 18.0h， 以66%的产率得到1-(4-氯苯基)-2,5-二甲基-1H-吡咯-3-羧酸
  参考文献：
  名称：

  Discovery of Novel Inhibitors of Uridine Diphosphate-N-Acetylenolpyruvylglucosamine Reductase (MurB) from Pseudomonas aeruginosa, an Opportunistic Infectious Agent Causing Death in Cystic Fibrosis Patients

  摘要：

  DOI：

  10.1021/acs.jmedchem.1c01684
• 作为产物：
  描述：

  乙酰乙酸乙酯 在 sodium hydride 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 4.5h， 生成 ethyl 1-(4-chlorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate
  参考文献：
  名称：

  新型吡咯衍生物作为潜在的针对结核分枝杆菌的ClpP1P2抑制剂的设计，合成和生物学评估

  摘要：

  为了发现结核分枝杆菌酪蛋白水解蛋白酶（ClpP1P2）的新型抑制剂，采用了虚拟高通量筛选和体外测定的组合策略，并使用了一种新的吡咯化合物1-（2-氯-6-氟苄基）- 2，发现5-二甲基-4-（（（苯乙基氨基）甲基）-1H-吡咯-3-羧酸酯对MIC 37表现出对H 37 Ra的抑制作用。为了更有效抗结核剂抑制ClpP1P2肽酶的发现结核分枝杆菌，一系列吡咯衍生物的设计并在此基础上的命中化合物合成。对合成的化合物进行了体外评估  还评估了针对ClpP1P2肽酶和抗结核活性的研究。最有前途的化合物2-（4-溴苯基）-N -（（1-（2-氯-6-氟苯基）-2，5-二甲基-1H-吡咯基）甲基）乙烷-1-胺盐酸盐7d，乙基4- （（（（4-溴苯乙基）氨基）甲基] -2,5-二甲基-1-苯基-1H-吡咯-3-羧酸盐酸盐13i，乙基1-（4-氯苯基）-4-（（（（2-氟苯乙基）氨基）甲基）-2-甲基-5-

  DOI：

  10.1016/j.bioorg.2018.06.004

文献信息

• Iron-catalyzed synthesis of polysubstituted pyrrolesvia [4C+1N] cyclization of 4-acetylenic ketones with primary amines
  作者：Yeming Wang、Xihe Bi、Dehua Li、Peiqiu Liao、Yidong Wang、Jin Yang、Qian Zhang、Qun Liu

  DOI：10.1039/c0cc03802d

  日期：——

  A highly efficient iron-catalyzed approach to polysubstituted pyrroles has been developed through the [4C+1N] cyclization of 4-acetylenic ketones with primary amines, leading to the synthesis of a variety of tetra- and fully-substituted pyrroles as well as fused pyrrole derivatives in good to excellent yields.

  通过 4-乙炔酮与伯胺的[4C+1N]环化反应，开发出了一种高效的铁催化多取代吡咯方法，从而以良好到极佳的收率合成了多种四取代和全取代吡咯以及融合吡咯衍生物。
• Screening of a Custom-Designed Acid Fragment Library Identifies 1-Phenylpyrroles and 1-Phenylpyrrolidines as Inhibitors of Notum Carboxylesterase Activity
  作者：William Mahy、Mikesh Patel、David Steadman、Hannah L. Woodward、Benjamin N. Atkinson、Fredrik Svensson、Nicky J. Willis、Alister Flint、Dimitra Papatheodorou、Yuguang Zhao、Luca Vecchia、Reinis R. Ruza、James Hillier、Sarah Frew、Amy Monaghan、Artur Costa、Magda Bictash、Magnus W. Walter、E. Yvonne Jones、Paul V. Fish

  DOI：10.1021/acs.jmedchem.0c00660

  日期：2020.9.10

  The Wnt family of proteins are secreted signaling proteins that play key roles in regulating cellular functions. Recently, carboxylesterase Notum was shown to act as a negative regulator of Wnt signaling by mediating the removal of an essential palmitoleate. Here we disclose two new chemical scaffolds that inhibit Notum enzymatic activity. Our approach was to create a fragment library of 250 acids for screening against Notum in a biochemical assay followed by structure determination by X-ray crystallography. Twenty fragments were identified as hits for Notum inhibition, and 14 of these fragments were shown to bind in the palmitoleate pocket of Notum. Optimization of 1-phenylpyrrole 20, guided by structure-based drug design, identified 20z as the most potent compound from this series. Similarly, the optimization of 1-phenylpyrrolidine 8 gave acid 26. This work demonstrates that inhibition of Notum activity can be achieved by small, drug-like molecules possessing favorable in vitro ADME profiles.