Methyl 2-amino-4,5-bis(4-chlorophenyl)thiophene-3-carboxylate | 1383628-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: Methyl 2-amino-4,5-bis(4-chlorophenyl)thiophene-3-carboxylate
• CAS: 1383628-25-8
• 化学式: C₁₈H₁₃Cl₂NO₂S
• 分子量: 378.279
• InChiKey: CCESPGCFCKAJMF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  Methyl 2-amino-4,5-bis(4-chlorophenyl)thiophene-3-carboxylate 在 水 、 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2,3-bis(4-chlorophenyl)-4-phenyl-5,7-dihydro-4H-thieno[2,3-b]pyridin-6-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53–MDM2 interaction. Part 2

  摘要：

  Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds displayed comparable p53-MDM2 binding inhibitory activities to that of Nutlin-3. Among them, compound 7a exhibited marked binding affinity (IC50 = 0.086 mu M). In addition, most target compounds showed potent anti-proliferation activities with IC50 values at low micromolar level. A good selective profile for wild-type p53 expression cell line was also observed. Molecular docking analysis was performed as well to predict possible binding modes of target compounds with MDM2. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.03.070
• 作为产物：
  描述：

  2,4'-二氯苯乙酮 在 吡啶 、 aluminum (III) chloride 、 四氯化钛 、 sulfur 、 二乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 Methyl 2-amino-4,5-bis(4-chlorophenyl)thiophene-3-carboxylate
  参考文献：
  名称：

  Identification of novel inhibitors of p53–MDM2 interaction facilitated by pharmacophore-based virtual screening combining molecular docking strategy

  摘要：

  针对p53-MDM2相互作用抑制剂的3D药效团模型已被开发出来。通过基于药效团的自家化合物数据库虚拟筛选与对接研究相结合，鉴定出了化合物MCL0527作为一种新型先导化合物（MDM2结合IC50 = 4.23 μM）。初步的结构优化获得了一些衍生物，它们具有更优的p53-MDM2结合抑制活性。此外，所有目标化合物均显示出对携带野生型p53的人类肿瘤细胞系具有强力的抗增殖效应，并表现出一般的选择性特征。

  DOI：

  10.1039/c2md20208e

文献信息

• Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53–MDM2 interaction. Part 1
  作者：Weisi Wang、Shihao Shangguan、Ni Qiu、Chunqi Hu、Lei Zhang、Yongzhou Hu

  DOI：10.1016/j.bmc.2013.03.061

  日期：2013.6

  A series of 3,4,5-trisubstituted aminothiophenes were designed, synthesized, and evaluated for their p53-MDM2 binding inhibitory potency and anti-proliferation activities against A549 and PC3 tumor cell lines. Fourteen compounds had appreciably improved MDM2 binding affinities than lead compound MCL0527 (3) and a few compounds showed comparable activities to that of Nutlin-3. Meanwhile, most of the 3,4,5-trisubstituted aminothiophenes displayed better or equivalent anti-proliferation activities against wild-type p53 cell line A549 compared to that of Nutlin-3. Over ten compounds exhibited desirable selective profiles of p53 status. Particularly, compounds 9, 16 and 18 displayed 22-, 6- and 22-fold selectivity of p53 status, respectively, much better than that of Nutlin-3 (fourfold). (C) 2013 Elsevier Ltd. All rights reserved.
• Design, synthesis and biological evaluation of novel 3,4,5-trisubstituted aminothiophenes as inhibitors of p53–MDM2 interaction. Part 2
  作者：Weisi Wang、Dan Lv、Ni Qiu、Lei Zhang、Chunqi Hu、Yongzhou Hu

  DOI：10.1016/j.bmc.2013.03.070

  日期：2013.6

  Five series of novel 3,4,5-trisubstituted aminothiophene derivatives and analogs were designed and synthesized based on our previous studies. All target compounds were evaluated for their p53-MDM2 binding inhibitory activities and anti-proliferation activities against A549 and PC3 tumor cell lines. Twelve compounds displayed comparable p53-MDM2 binding inhibitory activities to that of Nutlin-3. Among them, compound 7a exhibited marked binding affinity (IC50 = 0.086 mu M). In addition, most target compounds showed potent anti-proliferation activities with IC50 values at low micromolar level. A good selective profile for wild-type p53 expression cell line was also observed. Molecular docking analysis was performed as well to predict possible binding modes of target compounds with MDM2. (C) 2013 Elsevier Ltd. All rights reserved.
• Identification of novel inhibitors of p53–MDM2 interaction facilitated by pharmacophore-based virtual screening combining molecular docking strategy
  作者：Weisi Wang、Xiaolei Zhu、Xueqin Hong、Lin Zheng、Hong Zhu、Yongzhou Hu

  DOI：10.1039/c2md20208e

  日期：——

  3D pharmacophore models for inhibitors of p53–MDM2 interaction were developed. The pharmacophore-based virtual screening of an in-house compound database combined with docking studies led to the identification of compound MCL0527 as a novel lead (MDM2 binding IC50 = 4.23 μM). Initial structure optimization yielded some derivatives with improved p53–MDM2 binding inhibitory activities. Furthermore, all target compounds showed potent anti-proliferative effect against human tumor cell lines with a generally selective profile on wild-type p53 cell lines.

  针对p53-MDM2相互作用抑制剂的3D药效团模型已被开发出来。通过基于药效团的自家化合物数据库虚拟筛选与对接研究相结合，鉴定出了化合物MCL0527作为一种新型先导化合物（MDM2结合IC50 = 4.23 μM）。初步的结构优化获得了一些衍生物，它们具有更优的p53-MDM2结合抑制活性。此外，所有目标化合物均显示出对携带野生型p53的人类肿瘤细胞系具有强力的抗增殖效应，并表现出一般的选择性特征。