[4-(2,5-二甲基-吡咯-1-基)-苯基]-乙酸 | 26165-63-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 中文名称: [4-(2,5-二甲基-吡咯-1-基)-苯基]-乙酸
• 中文别名: [4-（2,5-二甲基-吡咯-1-基）-苯基]-乙酸
• 英文名称: 2-(4-(2,5-dimethyl-1H-pyrrol-1-yl)phenyl)acetic acid
• 英文别名: [4-(2,5-Dimethyl-pyrrol-1-yl)-phenyl]-acetic acid；2-[4-(2,5-dimethylpyrrol-1-yl)phenyl]acetic acid
• CAS: 26165-63-9
• 化学式: C₁₄H₁₅NO₂
• mdl: MFCD01874280
• 分子量: 229.279
• InChiKey: OJKIUURDWZWFAM-UHFFFAOYSA-N

物化性质

• 熔点：
  110-112 °C
• 沸点：
  401.2±33.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.214
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P330,P363,P501
• 危险性描述：
  H302,H312,H332

反应信息

• 作为反应物：
  描述：

  [4-(2,5-二甲基-吡咯-1-基)-苯基]-乙酸 在 盐酸羟胺 作用下， 以 乙醇 、 水 为溶剂， 反应 24.0h， 生成 对氨基苯乙酸
  参考文献：
  名称：

  Bruekelman, Stephen P.; Leach, (Miss) Susan E.; Meakins, G. Denis, Journal of the Chemical Society. Perkin transactions I, 1984, p. 2801 - 2807

  摘要：

  DOI：
• 作为产物：
  描述：

  2-<4-(2,5-dimethylpyrrol-1-yl)benzilidene>-1,3-dithian 在 氢氧化钾 、 mercury dichloride 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 [4-(2,5-二甲基-吡咯-1-基)-苯基]-乙酸
  参考文献：
  名称：

  Bruekelman, Stephen P.; Leach, (Miss) Susan E.; Meakins, G. Denis, Journal of the Chemical Society. Perkin transactions I, 1984, p. 2801 - 2807

  摘要：

  DOI：

文献信息

• C–H Alkenylation of Heteroarenes: Mechanism, Rate, and Selectivity Changes Enabled by Thioether Ligands
  作者：Bradley J. Gorsline、Long Wang、Peng Ren、Brad P. Carrow

  DOI：10.1021/jacs.7b03887

  日期：2017.7.19

  catalytic intermediate in these reactions may also account for unusual catalyst-controlled site selectivity wherein C–H alkenylation of five-atom heteroarenes can occur under electronic control with thioether ligands even when this necessarily involves reaction at a more hindered C–H bond. The thioether effect also enables short reaction times under mild conditions for many O-, S-, and N-heteroarenes (55 examples)

  已确定硫醚辅助配体可以大大促进O-，S-和N的C–H烯基化-杂芳烃。动力学数据表明，硫醚-Pd催化的反应比经典的无配体系统快800倍之多。此外，机理研究表明，C–H键的裂解是限制周转的步骤，硫醚配位时的速率加速与该关键步骤从中性途径向阳离子途径的变化相关。在这些反应中形成阳离子型，低配位的催化中间体也可能说明了催化剂控制位点的异常，其中五原子杂芳烃的CH链烯基化可以在硫代配体的电子控制下发生，即使这必然涉及在更阻碍了CH键的键合。硫醚效应还使得许多O-，S-和N-杂芳烃（55个实例），包括晚期药物衍生化的实例。
• A Detective Story in Drug Discovery: Elucidation of a Screening Artifact Reveals Polymeric Carboxylic Acids as Potent Inhibitors of RNA Polymerase
  作者：Weixing Zhu、Matthias Groh、Jörg Haupenthal、Rolf W. Hartmann

  DOI：10.1002/chem.201301289

  日期：2013.6.24

  Chasing the active impurity: In the validation of a screening hit it was discovered that a polymeric trace impurity was responsible for the biological activity. Such a side product can be formed with similar compounds. During the investigations it was discovered that the negatively charged macromolecule interacts very efficiently with the protein surface of E. coli RNAP via electrostatic interactions

  追逐活性杂质：在筛选命中的验证中，发现聚合的痕量杂质是造成生物活性的原因。这样的副产物可以由相似的化合物形成。在研究过程中，发现带负电荷的大分子通过静电相互作用与大肠杆菌RNAP的蛋白质表面非常有效地相互作用。
• Breukelman, Stephen P.; Meakins, G. Denis, Journal of the Chemical Society. Perkin transactions I, 1985, p. 1627 - 1636
  作者：Breukelman, Stephen P.、Meakins, G. Denis

  DOI：——

  日期：——
• Design, Synthesis, and Biological Evaluation of <i>N</i>-Carboxyphenylpyrrole Derivatives as Potent HIV Fusion Inhibitors Targeting gp41
  作者：Kun Liu、Hong Lu、Ling Hou、Zhi Qi、Cátia Teixeira、Florent Barbault、Bo-Tao Fan、Shuwen Liu、Shibo Jiang、Lan Xie

  DOI：10.1021/jm800869t

  日期：2008.12.25

  On the basis of the structures of small-molecule hits targeting the HIV-1 gp41, N-(4-carboxy-3-hydi-oxy)plieiiyl-2,5-dimethylpyl-role (2, NB-2), and N-(3-carboxy-4-chloro)phenylpyrrole (A(1), NB-64), 42 N-carboxyphenylpyrrole derivatives in two categories (A and B series) were designed and synthesized. We found that I I compounds exhibited promising anti-HIV-1 activity at micromolar level and their antiviral activity was correlated with their inhibitory activity on gp41 six-helix bundle formation, suggesting that these compounds block HIV fusion and entry by disrupting gp41 core formation. The structure-activity relationship and molecular docking analysis revealed that the carboxyl group Could interact with either Arg579 or Lys574 to form salt bridges and two methyl groups on the pyrrole ring were favorable for interaction with the residues in gp41 pocket. The most active compound, N-(3-carboxy-4-hydroxy)phenyl-2,5-dimethylpyrrole (A(12)), partially occupied the deep hydrophobic pocket, suggesting that enlarging the molecular size of A(12) could improve its binding affinity and anti-HIV-1 activity for further development as a small-molecule HIV fusion and entry inhibitor.
• Identification of non-peptidic cysteine reactive fragments as inhibitors of cysteine protease rhodesain
  作者：Danielle McShan、Stefan Kathman、Brittiney Lowe、Ziyang Xu、Jennifer Zhan、Alexander Statsyuk、Ifedayo Victor Ogungbe

  DOI：10.1016/j.bmcl.2015.08.074

  日期：2015.10

  Rhodesain, the major cathepsin L-like cysteine protease in the protozoan Trypanosoma brucei rhodesiense, the causative agent of African sleeping sickness, is a well-validated drug target. In this work, we used a fragment-based approach to identify inhibitors of this cysteine protease, and identified inhibitors of T. brucei. To discover inhibitors active against rhodesain and T. brucei, we screened a library of covalent fragments against rhodesain and conducted preliminary SAR studies. We envision that in vitro enzymatic assays will further expand the use of the covalent tethering method, a simple fragment-based drug discovery technique to discover covalent drug leads. (C) 2015 Elsevier Ltd. All rights reserved.