JG-03-14

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: JG-03-14
• 英文别名: Ethyl 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylate
• 化学式: C₁₅H₁₅Br₂NO₄
• 分子量: 433.096
• InChiKey: OMASOAOYMQBFGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  4

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester	127572-59-2	C15H17NO4	275.304

反应信息

• 作为反应物：
  描述：

  JG-03-14 在 1,3-二溴-5,5-二甲基海因 作用下， 生成 JG-05-4
  参考文献：
  名称：

  Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site

  摘要：

  报告了一系列与 3,5-二溴-4-(3,4-二甲氧基苯基)-1H-吡咯-2-羧酸有关的吡咯化合物的合成、生物学评价和分子建模，对 C-4 取代基进行了评估和优化。微管解聚活性的关键因素似乎是在原本疏水性的子口袋 A 中存在一个位置适当的 Cys241β 受体。

  DOI：

  10.1039/c2md20320k
• 作为产物：
  描述：

  4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid ethyl ester 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 氯仿 为溶剂， 以97%的产率得到JG-03-14
  参考文献：
  名称：

  Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells

  摘要：

  The 2,4-disubstituted and 2,3,4-trisubstituted brominated pyrroles were successfully prepared and demonstrated potent cytotoxicity against the growth of suspended murine and human tumors, i.e. leukemia and lymphomas, acute monocytic leukemia, and HeLa-S-3 uterine carcinoma. The brominated compounds were more selective in inhibiting the growth of tumors derived from human solid tumors. Nevertheless activity with some of the derivatives occurred in the human KB nasopharynx, SW-480 colon, and HCT ileum adenocarcinoma, and lung A549 carcinoma screens. In Tmolt(4) T cell leukemia cells DNA synthesis was reduced over 60 min from 25 to 100 mu M followed by RNA synthesis reduction. De novo purine synthesis was retarded with the regulatory enzyme PRPP-amino transferase being markedly inhibited with less effects dehydrogenase, dihydrofolate reductase,, nucleoside kinases. After 60 min incubations d[TTP] and d[GTP] pools were marginally reduced. In vitro ct-DNA studies that the agents may affect the DNA molecule itself with DNA viscosity and the Tmolt(4) studies suggest that DNA cross-linking of DNA strands may be present.

  DOI：

  10.1002/(sici)1521-4184(200001)333:1<3::aid-ardp3>3.0.co;2-4

文献信息

• [EN] POLYSUBSTITUTED PYRROLES HAVING MICROTUBULE-DISRUPTING, CYTOTOXIC AND ANTITUMOR ACTIVITIES AND METHDS OF USE THEREOF<br/>[FR] PYRROLES POLYSUBSTITUÉS AYANT DES ACTIVITÉS DE RUPTURE DE MICROTUBULES, CYTOTOXIQUES ET ANTITUMORALES ET MÉTHODES LES UTILISANT
  申请人：KELLOGG GLEN E

  公开号：WO2015039073A1

  公开（公告）日：2015-03-19

  The present invention provides polysubstituted pyrrole compounds, pharmaceutically effective salts, prodrugs, solvates and hydrates thereof, having antimitotic, antiproliferative and cytotoxic activity, activity against cells expressing the drug efflux protein, P-glycoprotein, or cells expressing the β-ΙΙΙ isotype of tubulin and antitumor activity. Also provided are methods of utilizing these compounds for inhibiting the proliferation of cancer cells as well as their medical use, in particular for treating cancer, including drug resistant cancer.

  本发明提供了多取代吡咯化合物，药效盐、前药、溶剂合物和水合物，具有抗有丝分裂、抗增殖和细胞毒活性，对表达药物外流蛋白P-糖蛋白的细胞、或表达β-ΙΙΙ微管蛋白亚型的细胞具有活性，并具有抗肿瘤活性。还提供了利用这些化合物抑制癌细胞增殖的方法，以及它们的医疗用途，特别是用于治疗癌症，包括耐药性癌症。
• POLYSUBSTITUTED PYRROLES HAVING MICROTUBULE-DISRUPTING, CYTOTOXIC AND ANTITUMOR ACTIVITIES AND METHODS OF USE THEREOF
  申请人：KELLOGG Glen E.

  公开号：US20160297757A1

  公开（公告）日：2016-10-13

  The present invention provides polysubstituted pyrrole compounds, pharmaceutically effective salts, prodrugs, solvates and hydrates thereof, having antimitotic, antiproliferative and cytotoxic activity, activity against cells expressing the drug efflux protein, P-glycoprotein, or cells expressing the β-III isotype of tubulin and antitumor activity. Also provided are methods of utilizing these compounds for inhibiting the proliferation of cancer cells as well as their medical use, in particular for treating cancer, including drug resistant cancer.
• US9944597B2
  申请人：——

  公开号：US9944597B2

  公开（公告）日：2018-04-17
• Developing novel C-4 analogues of pyrrole-based antitubulin agents: weak but critical hydrogen bonding in the colchicine site
  作者：Chenxiao Da、Nakul Telang、Kayleigh Hall、Emily Kluball、Peter Barelli、Kara Finzel、Xin Jia、John T. Gupton、Susan L. Mooberry、Glen E. Kellogg

  DOI：10.1039/c2md20320k

  日期：——

  The synthesis, biological evaluation and molecular modeling of a series of pyrrole compounds related to 3,5-dibromo-4-(3,4-dimethoxyphenyl)-1H-pyrrole-2-carboxylic acid that evaluates and optimizes C-4 substituents are reported. The key factor for microtubule depolymerization activity appears to be the presence of an appropriately positioned acceptor for Cys241β in the otherwise hydrophobic subpocket A.

  报告了一系列与 3,5-二溴-4-(3,4-二甲氧基苯基)-1H-吡咯-2-羧酸有关的吡咯化合物的合成、生物学评价和分子建模，对 C-4 取代基进行了评估和优化。微管解聚活性的关键因素似乎是在原本疏水性的子口袋 A 中存在一个位置适当的 Cys241β 受体。
• Synthesis and Cytotoxicity of 2,4-Disubstituted and 2,3,4-Trisubstituted Brominated Pyrroles in Murine and Human Cultured Tumor Cells
  作者：John T. Gupton、Bruce S. Burham、Keith Krumpe、Karen Du、James A. Sikorski、Amy E. Warren、Cheryl R. Barnes、Iris. H. Hall

  DOI：10.1002/(sici)1521-4184(200001)333:1<3::aid-ardp3>3.0.co;2-4

  日期：2000.1

  The 2,4-disubstituted and 2,3,4-trisubstituted brominated pyrroles were successfully prepared and demonstrated potent cytotoxicity against the growth of suspended murine and human tumors, i.e. leukemia and lymphomas, acute monocytic leukemia, and HeLa-S-3 uterine carcinoma. The brominated compounds were more selective in inhibiting the growth of tumors derived from human solid tumors. Nevertheless activity with some of the derivatives occurred in the human KB nasopharynx, SW-480 colon, and HCT ileum adenocarcinoma, and lung A549 carcinoma screens. In Tmolt(4) T cell leukemia cells DNA synthesis was reduced over 60 min from 25 to 100 mu M followed by RNA synthesis reduction. De novo purine synthesis was retarded with the regulatory enzyme PRPP-amino transferase being markedly inhibited with less effects dehydrogenase, dihydrofolate reductase,, nucleoside kinases. After 60 min incubations d[TTP] and d[GTP] pools were marginally reduced. In vitro ct-DNA studies that the agents may affect the DNA molecule itself with DNA viscosity and the Tmolt(4) studies suggest that DNA cross-linking of DNA strands may be present.