3-(4-nitro-benzenesulfonylamino)thiophene-2-carboxylic acid | 1155986-73-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(4-nitro-benzenesulfonylamino)thiophene-2-carboxylic acid
• 英文别名: 3-[(4-Nitrophenyl)sulfonylamino]thiophene-2-carboxylic acid
• CAS: 1155986-73-4
• 化学式: C₁₁H₈N₂O₆S₂
• 分子量: 328.326
• InChiKey: PYIHKNKIURKPLO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  166
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  L-NAME 、 3-(4-nitro-benzenesulfonylamino)thiophene-2-carboxylic acid 在 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 16.33h， 以3%的产率得到(S)-5-N(G)-nitro-guanidino-2-{[3-(4-nitro-benzenesulfonylamino)thiophene-2-carbonyl]amino}pentanoic acid methyl ester
  参考文献：
  名称：

  Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction

  摘要：

  We report the molecular design and synthesis of EG00229,2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis Studies localized VEGF-A binding in the NRP1 b1 domain and it peptide Fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells wits reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1.

  DOI：

  10.1021/jm901755g
• 作为产物：
  描述：

  3-(4-nitro-benzenesulfonylamino)thiophene-2-carboxylic acid methyl ester 在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-(4-nitro-benzenesulfonylamino)thiophene-2-carboxylic acid
  参考文献：
  名称：

  新型1,2,4-恶二唑-磺酰胺基化合物的合成和SAR研究，这些化合物可作为结直肠癌治疗的潜在抗癌药。

  摘要：

  设计，合成和评估了一系列基于1,2,4-恶二唑的取代化合物，并将其作为靶向碳酸酐酶IX（CAIX）的抗癌剂。初步的结构活性分析表明，1,2,4-恶二唑的噻唑/噻吩-磺酰胺共轭物显示出有效的抗癌活性，且μM效力低。化合物OX12表现出抗增殖活性（IC50 = 11.1 µM），并对与肿瘤相关的CAIX具有明显的抑制作用（IC50 = 4.23 µM）。因此，对OX12进行了结构优化，并合成并评估了其SAR定向衍生物（OX17-27）。通过这种迭代，化合物OX27的抗增殖作用几乎增加了两倍（IC50 = 6.0 µM），可与临床药物阿霉素相比，并且对CAIX的效力明显更高（IC50 = 0.74 µM）。另外，OX27处理降低了CAIX的表达，诱导了细胞凋亡和ROS的产生，抑制了结肠癌细胞的集落形成和迁移。我们的研究为进一步优化已鉴定的OX27提供了临床前理由，OX27是可能治疗CRC的合适先导。

  DOI：

  10.1016/j.bioorg.2020.103754

文献信息

• Small Molecule Inhibitors of the Neuropilin-1 Vascular Endothelial Growth Factor A (VEGF-A) Interaction
  作者：Ashley Jarvis、Charles K. Allerston、Haiyan Jia、Birger Herzog、Acely Garza-Garcia、Natalie Winfield、Katie Ellard、Rehan Aqil、Rosemary Lynch、Chris Chapman、Basil Hartzoulakis、James Nally、Mark Stewart、Lili Cheng、Malini Menon、Michelle Tickner、Snezana Djordjevic、Paul C. Driscoll、Ian Zachary、David L. Selwood

  DOI：10.1021/jm901755g

  日期：2010.3.11

  We report the molecular design and synthesis of EG00229,2, the first small molecule ligand for the VEGF-A receptor neuropilin 1 (NRP1) and the structural characterization of NRP1-ligand complexes by NMR spectroscopy and X-ray crystallography. Mutagenesis Studies localized VEGF-A binding in the NRP1 b1 domain and it peptide Fragment of VEGF-A was shown to bind at the same site by NMR, providing the basis for small molecule design. Compound 2 demonstrated inhibition of VEGF-A binding to NRP1 and attenuated VEGFR2 phosphorylation in endothelial cells. Inhibition of migration of endothelial cells was also observed. The viability of A549 lung carcinoma cells wits reduced by 2, and it increased the potency of the cytotoxic agents paclitaxel and 5-fluorouracil when given in combination. These studies provide the basis for design of specific small molecule inhibitors of ligand binding to NRP1.
• Synthesis and SAR studies of novel 1,2,4-oxadiazole-sulfonamide based compounds as potential anticancer agents for colorectal cancer therapy
  作者：Farheen Shamsi、Phool Hasan、Aarfa Queen、Afzal Hussain、Parvez Khan、Bushra Zeya、Hannah M. King、Sandeep Rana、Jered Garrison、Mohamed F. Alajmi、M. Moshahid Alam Rizvi、Muhammad Zahid、Md Imtaiyaz Hassan、Mohammad Abid

  DOI：10.1016/j.bioorg.2020.103754

  日期：2020.5

  diverse series of 1,2,4-oxadiazoles based substituted compounds were designed, synthesized and evaluated as anticancer agents targeting carbonic anhydrase IX (CAIX). Initial structure-activity analysis suggested that the thiazole/thiophene-sulfonamide conjugates of 1,2,4-oxadiazoles exhibited potent anticancer activities with low μM potencies. Compound OX12 exhibited antiproliferative activity (IC50 =

  设计，合成和评估了一系列基于1,2,4-恶二唑的取代化合物，并将其作为靶向碳酸酐酶IX（CAIX）的抗癌剂。初步的结构活性分析表明，1,2,4-恶二唑的噻唑/噻吩-磺酰胺共轭物显示出有效的抗癌活性，且μM效力低。化合物OX12表现出抗增殖活性（IC50 = 11.1 µM），并对与肿瘤相关的CAIX具有明显的抑制作用（IC50 = 4.23 µM）。因此，对OX12进行了结构优化，并合成并评估了其SAR定向衍生物（OX17-27）。通过这种迭代，化合物OX27的抗增殖作用几乎增加了两倍（IC50 = 6.0 µM），可与临床药物阿霉素相比，并且对CAIX的效力明显更高（IC50 = 0.74 µM）。另外，OX27处理降低了CAIX的表达，诱导了细胞凋亡和ROS的产生，抑制了结肠癌细胞的集落形成和迁移。我们的研究为进一步优化已鉴定的OX27提供了临床前理由，OX27是可能治疗CRC的合适先导。