N-[4,8-bis(diethoxyphosphoryl)-2-naphthyl]-4-[[4-[[5-[[5-[[4,8-bis(diethoxyphosphoryl)-2-naphthyl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoylamino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide | 168287-01-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N-[4,8-bis(diethoxyphosphoryl)-2-naphthyl]-4-[[4-[[5-[[5-[[4,8-bis(diethoxyphosphoryl)-2-naphthyl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoylamino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide
• 英文别名: N-[4,8-bis(diethoxyphosphoryl)naphthalen-2-yl]-4-[[4-[[5-[[5-[[4,8-bis(diethoxyphosphoryl)naphthalen-2-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoyl]-1-methylpyrrol-3-yl]carbamoylamino]-1-methylpyrrole-2-carbonyl]amino]-1-methylpyrrole-2-carboxamide
• CAS: 168287-01-2
• 化学式: C₆₁H₇₆N₁₀O₁₇P₄
• 分子量: 1345.23
• InChiKey: LNQUSPQHVLNKLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  92
• 可旋转键数：
  30
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  319
• 氢给体数：
  6
• 氢受体数：
  17

反应信息

• 作为反应物：
  描述：

  N-[4,8-bis(diethoxyphosphoryl)-2-naphthyl]-4-[[4-[[5-[[5-[[4,8-bis(diethoxyphosphoryl)-2-naphthyl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoylamino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide 在 三甲基溴硅烷 、 水 作用下， 生成 carbonyl-bis[7-[4-(4-amino-1-methyl-1H-pyrrole-2-carbonylamino)-1-methyl-1H-pyrrole-2-carbonylamino]naphthalene-1,5-diphosphonic acid] tetrasodium salt
  参考文献：
  名称：

  Synthesis and binding mode of heterocyclic analogues of suramin inhibiting the human basic fibroblast growth factor

  摘要：

  The design, synthesis, and biological evaluation of a series of pyrrole and pyrazole congeners 2 of suramin, directed toward the development and identification of new ligands that complex the human fibroblast growth factor (bFGF), thereby inhibiting tumor-promoted angiogenesis, is reported. Compounds 2 were evaluated for their ability to inhibit binding of bFGF to its receptor, in vivo bFGF-induced angiogenesis, and neovascularization of the chorioallantoic membrane in comparison with suramin. These assays showed that ligands 2 exhibit moderate to good activity, comparable to that of suramin, and are less toxic than suramin itself. In this study, affinity data of ligands in combination with the crystal structure of bFGF were used to explain structure-affnity relationships and to gain an insight into the possible mode of ligand-protein interaction. Due to the lack of experimental structural data on the ligand-bFGF complexes, molecular mechanics techniques were used to obtain putative bioactive conformations and to generate docked complexes with the three-dimensional structure of bFGF. These experiments led to suggest that compounds 2 give rise to 1:1 complexes with bFGF through an unprecedented, bidentate attachment of their naphthylsulfonate groups to two main domains, commonly referred to as the heparin binding site and the receptor binding site, on bFGF, thus preventing the interaction of the growth factor with its receptor. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00052-2
• 作为产物：
  描述：

  N-[4,8-bis(diethoxyphosphoryl)naphthalen-2-yl]-1-methyl-4-nitropyrrole-2-carboxamide 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium acetate 作用下， 以 1,4-二氧六环 、 水 、 甲苯 为溶剂， 5.0 ℃ 、344.73 kPa 条件下， 生成 N-[4,8-bis(diethoxyphosphoryl)-2-naphthyl]-4-[[4-[[5-[[5-[[4,8-bis(diethoxyphosphoryl)-2-naphthyl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoyl]-1-methyl-pyrrol-3-yl]carbamoylamino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide
  参考文献：
  名称：

  Synthesis and binding mode of heterocyclic analogues of suramin inhibiting the human basic fibroblast growth factor

  摘要：

  The design, synthesis, and biological evaluation of a series of pyrrole and pyrazole congeners 2 of suramin, directed toward the development and identification of new ligands that complex the human fibroblast growth factor (bFGF), thereby inhibiting tumor-promoted angiogenesis, is reported. Compounds 2 were evaluated for their ability to inhibit binding of bFGF to its receptor, in vivo bFGF-induced angiogenesis, and neovascularization of the chorioallantoic membrane in comparison with suramin. These assays showed that ligands 2 exhibit moderate to good activity, comparable to that of suramin, and are less toxic than suramin itself. In this study, affinity data of ligands in combination with the crystal structure of bFGF were used to explain structure-affnity relationships and to gain an insight into the possible mode of ligand-protein interaction. Due to the lack of experimental structural data on the ligand-bFGF complexes, molecular mechanics techniques were used to obtain putative bioactive conformations and to generate docked complexes with the three-dimensional structure of bFGF. These experiments led to suggest that compounds 2 give rise to 1:1 complexes with bFGF through an unprecedented, bidentate attachment of their naphthylsulfonate groups to two main domains, commonly referred to as the heparin binding site and the receptor binding site, on bFGF, thus preventing the interaction of the growth factor with its receptor. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(98)00052-2

文献信息

• Synthesis and binding mode of heterocyclic analogues of suramin inhibiting the human basic fibroblast growth factor
  作者：Fabrizio Manetti、Valentina Cappello、Maurizio Botta、Federico Corelli、Nicola Mongelli、Giovanni Biasoli、Andrea Lombardi Borgia、Marina Ciomei

  DOI：10.1016/s0968-0896(98)00052-2

  日期：1998.7

  The design, synthesis, and biological evaluation of a series of pyrrole and pyrazole congeners 2 of suramin, directed toward the development and identification of new ligands that complex the human fibroblast growth factor (bFGF), thereby inhibiting tumor-promoted angiogenesis, is reported. Compounds 2 were evaluated for their ability to inhibit binding of bFGF to its receptor, in vivo bFGF-induced angiogenesis, and neovascularization of the chorioallantoic membrane in comparison with suramin. These assays showed that ligands 2 exhibit moderate to good activity, comparable to that of suramin, and are less toxic than suramin itself. In this study, affinity data of ligands in combination with the crystal structure of bFGF were used to explain structure-affnity relationships and to gain an insight into the possible mode of ligand-protein interaction. Due to the lack of experimental structural data on the ligand-bFGF complexes, molecular mechanics techniques were used to obtain putative bioactive conformations and to generate docked complexes with the three-dimensional structure of bFGF. These experiments led to suggest that compounds 2 give rise to 1:1 complexes with bFGF through an unprecedented, bidentate attachment of their naphthylsulfonate groups to two main domains, commonly referred to as the heparin binding site and the receptor binding site, on bFGF, thus preventing the interaction of the growth factor with its receptor. (C) 1998 Elsevier Science Ltd. All rights reserved.