3-hydroxy-4-(1H-pyrrol-1-yl)benzoic acid | 860791-86-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 3-hydroxy-4-(1H-pyrrol-1-yl)benzoic acid
• 英文别名: 3-Hydroxy-4-pyrrol-1-ylbenzoic acid
• CAS: 860791-86-2
• 化学式: C₁₁H₉NO₃
• mdl: MFCD09755782
• 分子量: 203.197
• InChiKey: CXZJKVGDYOJCSA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  62.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-4-(1H-pyrrol-1-yl)benzoic acid 在 吗啉 、 四(三苯基膦)钯 、 五氯化磷 、 sodium hydride 、 cesium fluoride 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.5h， 生成 (+/-)-3-ethoxycarbonyl-6-(naphth-1-yl)pyrrolo[2,1-d][1,5]benzoxazepin-7(6H)-one
  参考文献：
  名称：

  Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of Their Drug Target

  摘要：

  We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their potential as novel anticancer agents. The core structure of the apoptotic agent 6 was investigated, and the SARs were expanded with the design and synthesis of several analogues. To define the apoptotic mechanism of the new compounds and the localization of their drug target, two analogues of 6 were designed and synthesized to delineate events leading to JNK activation. The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK. Plasma membrane permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting that the pyrrolo-1,5-benzoxazepine molecular target is intracellular. Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters.

  DOI：

  10.1021/jm049402y
• 作为产物：
  描述：

  4-氨基-3-羟基苯甲酸甲酯 在 lithium hydroxide monohydrate 、 水 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.25h， 生成 3-hydroxy-4-(1H-pyrrol-1-yl)benzoic acid
  参考文献：
  名称：

  作为有效和选择性 Sirt6 激活剂的吡咯并[1,2-a]喹喔啉基衍生物的设计、合成和药理学评价

  摘要：

  Sirt6 激活已成为治疗各种人类疾病的有前景的药物靶点，但目前仅报道了有限的 Sirt6 激活剂。在此，一系列新型吡咯并[1,2- a ]喹喔啉衍生物已被鉴定为具有低细胞毒性的有效、选择性Sirt6激活剂。 Sirt6 敲低研究结果验证了此类 Sirt6 激活剂的靶向作用。对接研究表明， 38侧链上的质子化氮与 Trp188 形成 π 阳离子相互作用，进一步将其稳定在这个扩展的结合袋中。新化合物35、36、38、46、47和50强烈抑制 LPS 诱导的促炎细胞因子/趋化因子的产生，而38也显着抑制 SARS - CoV -2 感染，EC 50值为 9.3 μM。此外，化合物36显着抑制癌细胞集落形成。这些新分子可以作为有用的药理学工具或针对癌症、炎症和传染病的潜在疗法。

  DOI：

  10.1016/j.ejmech.2022.114998

文献信息

• Pyrrolo[1,5]benzoxa(thia)zepines as a New Class of Potent Apoptotic Agents. Biological Studies and Identification of an Intracellular Location of Their Drug Target
  作者：Margaret M. Mc Gee、Sandra Gemma、Stefania Butini、Anna Ramunno、Daniela M. Zisterer、Caterina Fattorusso、Bruno Catalanotti、Gagan Kukreja、Isabella Fiorini、Claudio Pisano、Carla Cucco、Ettore Novellino、Vito Nacci、D. Clive Williams、Giuseppe Campiani

  DOI：10.1021/jm049402y

  日期：2005.6.1

  We have recently developed five novel pyrrolo-1,5-benzoxazepines as proapoptotic agents. Their JNK-dependent induction of apoptosis in tumor cells suggested their potential as novel anticancer agents. The core structure of the apoptotic agent 6 was investigated, and the SARs were expanded with the design and synthesis of several analogues. To define the apoptotic mechanism of the new compounds and the localization of their drug target, two analogues of 6 were designed and synthesized to delineate events leading to JNK activation. The cell-penetrating compound 16 induced apoptosis in tumor cells, while its nonpenetrating analogue, 17, was incapable of inducing apoptosis or activating JNK. Plasma membrane permeabilization of tumor cells resulted in 17-induced JNK activation, suggesting that the pyrrolo-1,5-benzoxazepine molecular target is intracellular. Interestingly, compound 6 displayed cytotoxic activity against a panel of human tumor cell lines but demonstrated negligible toxicity in vivo with no effect on the animals' hematology parameters.
• Design, synthesis, and pharmacological evaluations of pyrrolo[1,2-a]quinoxaline-based derivatives as potent and selective sirt6 activators
  作者：Jimin Xu、Shuizhen Shi、Gang Liu、Xuping Xie、Jun Li、Andrew A. Bolinger、Haiying Chen、Wenbo Zhang、Pei-Yong Shi、Hua Liu、Jia Zhou

  DOI：10.1016/j.ejmech.2022.114998

  日期：2023.1

  target for the treatment of various human diseases, while only limited Sirt6 activators have been reported. Herein, a series of novel pyrrolo[1,2-a]quinoxaline-based derivatives have been identified as potent and selective Sirt6 activators with low cytotoxicity. Sirt6-knockdown findings have validated the on-target effects of this class of Sirt6 activators. Docking studies indicate the protonated nitrogen

  Sirt6 激活已成为治疗各种人类疾病的有前景的药物靶点，但目前仅报道了有限的 Sirt6 激活剂。在此，一系列新型吡咯并[1,2- a ]喹喔啉衍生物已被鉴定为具有低细胞毒性的有效、选择性Sirt6激活剂。 Sirt6 敲低研究结果验证了此类 Sirt6 激活剂的靶向作用。对接研究表明， 38侧链上的质子化氮与 Trp188 形成 π 阳离子相互作用，进一步将其稳定在这个扩展的结合袋中。新化合物35、36、38、46、47和50强烈抑制 LPS 诱导的促炎细胞因子/趋化因子的产生，而38也显着抑制 SARS - CoV -2 感染，EC 50值为 9.3 μM。此外，化合物36显着抑制癌细胞集落形成。这些新分子可以作为有用的药理学工具或针对癌症、炎症和传染病的潜在疗法。