Tetraethyl3-aminonaphthalene-1,5-diphosphonate | 198765-27-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: Tetraethyl3-aminonaphthalene-1,5-diphosphonate
• 英文别名: 4,8-bis(diethoxyphosphoryl)naphthalen-2-amine
• CAS: 198765-27-4
• 化学式: C₁₈H₂₇NO₆P₂
• 分子量: 415.363
• InChiKey: BVUGRJNJLAOFIZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  27
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  97.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Tetraethyl3-aminonaphthalene-1,5-diphosphonate 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
• 作为产物：
  描述：

  Tetraethyl3-nitronaphthalene-1,5-diphosphonate 在 palladium-carbon 盐酸 作用下， 以 甲醇 、 H2 、 乙醚 、 乙醇 为溶剂， 生成 Tetraethyl3-aminonaphthalene-1,5-diphosphonate
  参考文献：
  名称：

  Ureido derivatives of naphthalenephosphonic acids

  摘要：

  本发明的主题是具有以下公式（I）的萘磷酸尿素衍生物，其中m和n相同，均为1到4的整数；p和q相同，均为1到3的整数；R组相同，是自由或酯化的膦酸基团；以及其药物可接受的盐。

  公开号：

  US05700788A1

文献信息

• UREIDO DERIVATIVES OF NAPHTHALENEPHOSPHONIC ACIDS AND PROCESS FOR THEIR PREPARATION
  申请人：PHARMACIA S.p.A.

  公开号：EP0696287A1

  公开（公告）日：1996-02-14
• US5700788A
  申请人：——

  公开号：US5700788A

  公开（公告）日：1997-12-23
• [EN] UREIDO DERIVATIVES OF NAPHTHALENEPHOSPHONIC ACIDS AND PROCESS FOR THEIR PREPARATION<br/>[FR] DERIVES UREIDO DES ACIDES NAPHTALENE-PHOSPHONIQUES ET LEUR PROCEDE DE PREPARATION
  申请人：——

  公开号：WO1995023806A2

  公开（公告）日：1995-09-08

  [EN] Subject of the present invention are new ureido derivatives of naphthalenephosphonic acids having formula (I), wherein each of m and n, which are the same, is an integer of 1 to 4; each of p and q, which are the same, is an integer of 1 to 3; and each of the R groups, which are the same, is a free or esterified phosphonic acid group; and the pharmaceutically acceptable salts thereof.
  [FR] L'invention se rapporte à des nouveaux dérivés des acides naphtalène-phosphoniques de la formule générale (I) ainsi qu'aux sels pharmacologiquement acceptables de ceux-ci. Dans cette formule, m et n sont semblables, chacun représentant un nombre entier compris entre 1 et 4; p et q sont semblables, chacun représentant un nombre entier compris entre 1 et 3; et les groupes R sont semblables, chacun représentant un groupe acide phosphonique libre ou estérifié.
• 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.
• Ureido derivatives of naphthalenephosphonic acids
  申请人：Pharmacia & Upjohn S.p.A.

  公开号：US05700788A1

  公开（公告）日：1997-12-23

  Subject of the present invention are new ureido derivatives of naphthalenephosphonic acids having the following formula (I) ##STR1## wherein each of m and n, which are the same, is an integer of 1 to 4; each of p and q, which are the same, is an integer of 1 to 3; and each of the R groups, which are the same, is a free or esterified phosphonic acid group; and the pharmaceutically acceptable salts thereof.

  本发明涉及具有以下式（I）的萘磷酸尿素衍生物：##STR1## 其中m和n均为1至4的整数；p和q均为1至3的整数；R基团均为自由或酯化的膦酸基团；以及其药学上可接受的盐。