ethyl 3-((4,5-dichloro-2-nitrophenyl)amino)propanoate

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 3-((4,5-dichloro-2-nitrophenyl)amino)propanoate
• 英文别名: Ethyl 3-(4,5-dichloro-2-nitroanilino)propanoate；ethyl 3-(4,5-dichloro-2-nitroanilino)propanoate
• 化学式: C₁₁H₁₂Cl₂N₂O₄
• 分子量: 307.133
• InChiKey: JYRPZPOIPZTJKJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 3-((4,5-dichloro-2-nitrophenyl)amino)propanoate 在 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 水 为溶剂， 反应 3.0h， 生成 3-((4-chloro-2-nitro-5-((2-oxo-2,3-dihydro-1H-benzo[d]imidazol-5-yl)amino)phenyl)amino)propanoic acid
  参考文献：
  名称：

  Discovery of a novel B-cell lymphoma 6 (BCL6)–corepressor interaction inhibitor by utilizing structure-based drug design

  摘要：

  B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits la and 2a, we identified a novel BCL6corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC50 = 0.10 mu M, cell-based mammalian two-hybrid [M2H] assay IC50 = 0.72 mu M) by utilizing structure based drug design (SBDD) based on an X-ray crystal structure of la bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.037
• 作为产物：
  描述：

  1,2-二氯-4-氟-5-硝基苯 、 beta-丙氨酸乙酯盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 以85%的产率得到ethyl 3-((4,5-dichloro-2-nitrophenyl)amino)propanoate
  参考文献：
  名称：

  Discovery of a novel B-cell lymphoma 6 (BCL6)–corepressor interaction inhibitor by utilizing structure-based drug design

  摘要：

  B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits la and 2a, we identified a novel BCL6corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC50 = 0.10 mu M, cell-based mammalian two-hybrid [M2H] assay IC50 = 0.72 mu M) by utilizing structure based drug design (SBDD) based on an X-ray crystal structure of la bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.07.037

文献信息

• Discovery of a novel B-cell lymphoma 6 (BCL6)–corepressor interaction inhibitor by utilizing structure-based drug design
  作者：Takeshi Yasui、Takeshi Yamamoto、Nozomu Sakai、Kouhei Asano、Takafumi Takai、Yayoi Yoshitomi、Melinda Davis、Terufumi Takagi、Kotaro Sakamoto、Satoshi Sogabe、Yusuke Kamada、Weston Lane、Gyorgy Snell、Masashi Iwata、Masayuki Goto、Hiroshi Inooka、Jun-ichi Sakamoto、Yoshihisa Nakada、Yasuhiro Imaeda

  DOI：10.1016/j.bmc.2017.07.037

  日期：2017.9

  B-cell lymphoma 6 (BCL6) is a transcriptional repressor that can form complexes with corepressors via protein-protein interactions (PPIs). The complexes of BCL6 and corepressors play an important role in the formation of germinal centers (GCs), and differentiation and proliferation of lymphocytes. Therefore, BCL6-corepressor interaction inhibitors would be drug candidates for managing autoimmune diseases and cancer. Starting from high-throughput screening hits la and 2a, we identified a novel BCL6corepressor interaction inhibitor 8c (cell-free enzyme-linked immunosorbent assay [ELISA] IC50 = 0.10 mu M, cell-based mammalian two-hybrid [M2H] assay IC50 = 0.72 mu M) by utilizing structure based drug design (SBDD) based on an X-ray crystal structure of la bound to BCL6. Compound 8c also showed a good pharmacokinetic profile, which was acceptable for both in vitro and in vivo studies. (C) 2017 Elsevier Ltd. All rights reserved.