(S)-2-{[3-(benzo[1,2,5]thiadiazole-4-sulfonylamino)thiophene-2-carbonyl]amino}-5-guanidino(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)pentanoic acid methyl ester | 1207974-00-2

• 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: (S)-2-{[3-(benzo[1,2,5]thiadiazole-4-sulfonylamino)thiophene-2-carbonyl]amino}-5-guanidino(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)pentanoic acid methyl ester
• 英文别名: methyl (2S)-5-[[amino-[(2,2,4,6,7-pentamethyl-3H-1-benzofuran-5-yl)sulfonylamino]methylidene]amino]-2-[[3-(2,1,3-benzothiadiazol-4-ylsulfonylamino)thiophene-2-carbonyl]amino]pentanoate
• CAS: 1207974-00-2
• 化学式: C₃₁H₃₇N₇O₈S₄
• 分子量: 763.941
• InChiKey: OPEKVWMCCGVPJO-QFIPXVFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  50
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  294
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  (S)-2-{[3-(benzo[1,2,5]thiadiazole-4-sulfonylamino)thiophene-2-carbonyl]amino}-5-guanidino(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)pentanoic acid methyl ester 在 水 、 lithium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 0.5h， 生成 (S)-2-{[3-(benzo[1,2,5]thiadiazole-4-sulfonylamino)thiophene-2-carbonyl]amino}-5-guanidino(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)pentanoic acid
  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：

  methyl N^ω-((2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-yl)sulfonyl)-L-argininate 、 3-(benzo[1,2,5]thiadiazole-4-sulfonylamino)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 4.2h， 以100%的产率得到(S)-2-{[3-(benzo[1,2,5]thiadiazole-4-sulfonylamino)thiophene-2-carbonyl]amino}-5-guanidino(2,2,4,6,7-pentamethyldihydrobenzofuran-5-sulfonyl)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

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.