N-(3-hydroxy-4-methoxycarbonylphenyl)-2,5-dimethylpyrrole | 477871-45-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: N-(3-hydroxy-4-methoxycarbonylphenyl)-2,5-dimethylpyrrole
• 英文别名: methyl 4-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzenecarboxylate；methyl 4-(2,5-dimethylpyrrol-1-yl)-2-hydroxybenzoate
• CAS: 477871-45-7
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: REGPOQDITWHACV-UHFFFAOYSA-N

物化性质

• 熔点：
  58-61 °C
• 沸点：
  383.4±42.0 °C(Predicted)
• 密度：
  1.16±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  51.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(3-hydroxy-4-methoxycarbonylphenyl)-2,5-dimethylpyrrole 在 4-二甲氨基吡啶 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 反应 26.0h， 生成
  参考文献：
  名称：

  用于获得 mPTPB（一种结核病毒力因子）的选择性抑制剂的有机催化多组分反应。

  摘要：

  分枝杆菌蛋白酪氨酸磷酸酶 B (mPTPB) 对分枝杆菌在宿主中的存活和持久性至关重要。因此，mPTPB 的小分子抑制剂是潜在的抗结核药物。我们在吡咯、甲醛和苯胺之间开发了一种高效的有机催化多组分反应 (MCR)，提供了一种有效的选择性 mPTPB 抑制剂，IC(50) 值为 1.5 muM，特异性大于 50 倍。我们的研究提供了使用有机催化作为获取 PTP 抑制剂的发现工具的成功例子。

  DOI：

  10.1039/c3cc38961h
• 作为产物：
  描述：

  2,5-己二酮 、 2-羟基-4-氨基苯甲酸甲酯 在 溶剂黄146 作用下， 反应 0.17h， 以62%的产率得到N-(3-hydroxy-4-methoxycarbonylphenyl)-2,5-dimethylpyrrole
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of N-Carboxyphenylpyrrole Derivatives as Potent HIV Fusion Inhibitors Targeting gp41

  摘要：

  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.

  DOI：

  10.1021/jm800869t

文献信息

• [EN] PYRROL-1 -YL BENZOIC ACID DERIVATES USEFUL AS MYC INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE PYRROL-1-YL-BENZOÏQUE UTILES EN TANT QU'INHIBITEURS DE MYC
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2014071247A1

  公开（公告）日：2014-05-08

  The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.

  本发明提供了式(I-A)、(I-B)和(I-C)的化合物、药用可接受的盐及其药用组合物。本发明的化合物可用于抑制Myc（例如，c-Myc）活性。本发明进一步提供了使用所述化合物治疗Myc介导的疾病（例如，癌症和其他增殖性疾病）的方法。本发明还提供了用于识别Myc抑制剂的检测方法。
• PYRROL-1-YL BENZOIC ACID DERIVATIVES USEFUL AS MYC INHIBITORS
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20150291521A1

  公开（公告）日：2015-10-15

  The present invention provides compounds of Formula (I-A), (I-B), and (I-C), pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof. Compounds of the present invention are useful for inhibiting Myc (e.g., c-Myc) activity. The present invention further provides methods of using the compounds described herein for treating Myc-mediated disorders (e.g., cancer and other proliferative diseases). The present invention also provides assays for identifying Myc inhibitors.

  本发明提供了公式(I-A)、(I-B)和(I-C)的化合物，其药学上可接受的盐以及其制药组合物。本发明的化合物可用于抑制Myc（例如c-Myc）的活性。本发明还提供了使用本文所描述的化合物治疗Myc介导的疾病（例如癌症和其他增殖性疾病）的方法。本发明还提供了用于鉴定Myc抑制剂的检测方法。
• METHOD FOR IDENTIFYING MYC INHIBITORS
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP2917203B1

  公开（公告）日：2019-04-03
• US9567301B2
  申请人：——

  公开号：US9567301B2

  公开（公告）日：2017-02-14
• 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.