tetraethyl [(pyridin-3-ylamino)methylene]bis(phosphonate)

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: tetraethyl [(pyridin-3-ylamino)methylene]bis(phosphonate)
• 英文别名: N-[bis(diethoxyphosphoryl)methyl]pyridin-3-amine
• 化学式: C₁₄H₂₆N₂O₆P₂
• 分子量: 380.318
• InChiKey: HIJHEOCYYSJRJT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  96
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tetraethyl [(pyridin-3-ylamino)methylene]bis(phosphonate) 在 盐酸 作用下， 生成 [(3-pyridinylamino)methylene]-1,1-bisphosphonate
  参考文献：
  名称：

  3-D QSAR研究双膦酸盐对利什曼原虫主要法呢基焦磷酸合酶的抑制作用。

  摘要：

  我们报告了作为利什曼原虫主要甲羟戊酸/异戊二烯生物合成途径酶，法呢基焦磷酸合酶的抑制剂的62二膦酸盐的活性。所研究的化合物具有约100 nM至约80 microM（相当于K（i）值低至10 nM）的活性（IC（50）值）。发现活性最高的化合物是唑来膦酸盐（据报道其单晶X射线结构），吡啶基-乙烷-1-羟基-1,1-双膦酸酯或吡啶甲基氨基亚甲基双膦酸酯。但是，N-脂环族氨基亚甲基双膦酸酯（如茚满膦酸酯）（N-环庚基氨基亚甲基双膦酸酯）以及含有短（n = 4、5）烷基链的脂族氨基亚甲基双膦酸酯也具有活性，IC（50）值在200-1700 nM范围内（对应于大约20-170 nM的K（i）值）。含有更长或多个（N，N-）烷基取代基的双膦酸酯是无活性的，环上缺少邻或间氮原子或具有多个卤素取代基或对氨基的芳香族化合物也是如此。为了将这些观察结果放在更定量的结构基础上，我们使用了三维定量结构-活性关系技

  DOI：

  10.1021/jm0302344
• 作为产物：
  描述：

  3-氨基吡啶 、 原甲酸三乙酯 、 亚磷酸二乙酯 生成 tetraethyl [(pyridin-3-ylamino)methylene]bis(phosphonate)
  参考文献：
  名称：

  3-D QSAR研究双膦酸盐对利什曼原虫主要法呢基焦磷酸合酶的抑制作用。

  摘要：

  我们报告了作为利什曼原虫主要甲羟戊酸/异戊二烯生物合成途径酶，法呢基焦磷酸合酶的抑制剂的62二膦酸盐的活性。所研究的化合物具有约100 nM至约80 microM（相当于K（i）值低至10 nM）的活性（IC（50）值）。发现活性最高的化合物是唑来膦酸盐（据报道其单晶X射线结构），吡啶基-乙烷-1-羟基-1,1-双膦酸酯或吡啶甲基氨基亚甲基双膦酸酯。但是，N-脂环族氨基亚甲基双膦酸酯（如茚满膦酸酯）（N-环庚基氨基亚甲基双膦酸酯）以及含有短（n = 4、5）烷基链的脂族氨基亚甲基双膦酸酯也具有活性，IC（50）值在200-1700 nM范围内（对应于大约20-170 nM的K（i）值）。含有更长或多个（N，N-）烷基取代基的双膦酸酯是无活性的，环上缺少邻或间氮原子或具有多个卤素取代基或对氨基的芳香族化合物也是如此。为了将这些观察结果放在更定量的结构基础上，我们使用了三维定量结构-活性关系技

  DOI：

  10.1021/jm0302344

文献信息

• Aminodiphosphonate apolipoprotein e modulators
  申请人：Phan Trung Hieu

  公开号：US20050075317A1

  公开（公告）日：2005-04-07

  The present invention relates to methods of use of aminodiphosphonate to modulate apolipoprotein E levels and the use of such compounds in therapy, including cardiovascular and neurological disease states.

  本发明涉及使用氨基二膦酸盐来调节载脂蛋白E水平的方法，并将这些化合物用于治疗心血管和神经系统疾病状态。
• Effects of Bisphosphonates on the Growth of <i>Entamoeba histolytica</i> and <i>Plasmodium </i>Species in Vitro and in Vivo
  作者：Subhash Ghosh、Julian M. W. Chan、Christopher R. Lea、Gary A. Meints、Jared C. Lewis、Zev S. Tovian、Ryan M. Flessner、Timothy C. Loftus、Iris Bruchhaus、Howard Kendrick、Simon L. Croft、Robert G. Kemp、Seiki Kobayashi、Tomoyoshi Nozaki、Eric Oldfield

  DOI：10.1021/jm030084x

  日期：2004.1.1

  The effects of a series of 102 bisphosphonates on the inhibition of growth of Entamoeba histolytica and Plasmodium falciparum in vitro have been determined, and selected compounds were further investigated for their in vivo activity. Forty-seven compounds tested were active (IC50 < 200 muM) versus E. histolytica growth in vitro. The most active compounds (IC50 similar to 4-9 muM) were nitrogen-containing bisphosphonates with relatively large aromatic side chains. Simple n-alkyl-1-hydroxy-1,1-bisphosphonates, known inhibitors of the enzyme farnesylpyrophosphate (FPP) synthase, were also active, with optimal activity being found with C9-C10 side chains. However, numerous other nitrogen-containing bisphosphonates known to be potent FPP synthase inhibitors, such as risedronate or pamidronate, had little or no activity. Several pyridine-derived bisphosphonates were quite active (IC50 similar to 10-20 muM), and this activity was shown to correlate with the basicity of the aromatic group, with activity decreasing with increasing pK(a) values. The activities of all compounds were tested versus a human nasopharyngeal carcinoma (KB) cell line to enable an estimate of the therapeutic index (TI). Five bisphosphonates were selected and then screened for their ability to delay the development of amebic liver abscess formation in an E. histolytica infected hamster model. Two compounds were found to decrease liver abscess formation at 10 mg/kg ip with little or no effect on normal liver mass. With P. falciparum, 35 compounds had IC50 values <200 muM in an in vitro assay. The most active compounds were also simple n-alkyl-1-hydroxy-1,1-bisphosphonates, having IC50 values around 1 muM. Five compounds were again selected for in vivo investigation in a Plasmodium berghei ANKA BALB/c mouse suppressive test. The most active compound, a C9 n-alkyl side chain containing bisphosphonate, caused an 80% reduction in parasitemia with no overt toxicity. Taken together, these results show that bisphosphonates appear to be useful lead compounds for the development of novel antiamebic and antimalarial drugs.
• Nano ZnO catalyzed green synthesis and cytotoxic assay of pyridinyl and pyrimidinyl bisphosphonates
  作者：Gundluru Mohan、Sarva Santhisudha、Nadiveedhi Maheshwara Reddy、Tellamekala Sreekanth、Sudileti Murali、Cirandur Suresh Reddy

  DOI：10.1007/s00706-017-2000-2

  日期：2017.10

  A straight forward approach ensuring the anchoring of bisphosphonate moiety onto various pyridinyl and pyrimidinyl amines is described by the three-component reaction of an amine, diethyl phosphite, and triethyl orthoformate in the presence of catalytic amount of nano ZnO as an environmentally benign and heterogeneous catalyst under solvent-free microwave irradiation conditions. All the synthesized compounds are evaluated for anti-cell proliferation activity against human breast (MCF-7), prostate (DU-145), osteosarcoma (MG-63), fibrosarcoma (HT-1080), multiple myeloma (RPMI-8226) cancer cell lines using sulforhodamine-B (SRB) assay method, and adriamycin as a reference drug. All the title compounds showed promising cytotoxic activity on the five cell lines. One compound was two times more active than adriamycin on all the five cancer cell lines.[GRAPHICS].
• NOVEL METHYLENEBISPHOSPHONIC ACID DERIVATIVES
  申请人：LEIRAS OY

  公开号：EP0563107B1

  公开（公告）日：2000-05-03
• AMINODIPHOSPHONATE APOLIPOPROTEIN E MODULATORS
  申请人：Ilex Products, Inc.

  公开号：EP1482897A2

  公开（公告）日：2004-12-08