[[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate

• 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: [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate
• 英文别名: N-(5-chloro-2-pyridyl)aminomethane-1,1-diphosphonic acid；(5-chloropyridin-2-ylamino)methylenebisphosphonic acid；N-(5-chloropyrid-2-yl)aminomethylenebisphosphonic acid；N-2-(5-chloropyridyl)aminomethylenebisphosphonic acid；N-2-(5-chloropyridyl)aminomethyldiphosphonic acid；[[(5-Chloropyridin-1-ium-2-yl)amino]-phosphonomethyl]-hydroxyphosphinate
• 化学式: C₆H₉ClN₂O₆P₂
• 分子量: 302.548
• InChiKey: BNMYZGAZFGNKTH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.6
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  140
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-氨基吡啶 、 水 、 [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate 反应 24.0h， 生成
  参考文献：
  名称：

  吡啶基侧链碱度与 5-卤素取代的（吡啶-2-基）氨基甲烷-1,1-二膦酸的 Z/E 偏好之间关系的 X 射线证据；对溶液中金属离子配位的影响

  摘要：

  三种盐（1-a-3-a）的晶体结构，5-氯（1）、5溴（2）和5-碘（3）取代（吡啶-2-基）氨基甲烷-1反应的产物,1-二膦酸和 4-氨基吡啶通过单晶 X 射线衍射测定，并讨论了分子几何形状和固态组织。在所有 1-a-3-a 中，与母体两性离子相比，双膦酸二价阴离子在 C2 -N1 键方面采用相反的 (E) 构象。这提供了进一步的证据，即涉及环外和吡啶鎓 N 原子作为质子供体和膦酸/膦酸酯基团的 O 原子作为受体的分子间 N−H…O 氢键在稳定这种特殊的 Z 构象方面起着重要作用。酸的亚类。还研究了 [(5-iodopyridin-2-yl)amino]methane-1,1-diphosphonic acid (3) 的溶液行为和络合物形成能力。化合物 3 以 Z/E 混合物的形式存在于溶液中。然而，与 1 和 2 相比，3 中围绕 C2 -N1 键旋转的障碍较低。这对于 Zn(II)、Mg(II)

  DOI：

  10.3998/ark.5550190.0013.412
• 作为产物：
  描述：

  N-(5-chloropyridin-2-yl)formamide 在 甲醇 、 三氟甲磺酸三甲基硅酯 作用下， 以 乙醚 、 二氯甲烷 为溶剂， 20.0 ℃ 、66.66 Pa 条件下， 生成 [[(5-chloro-2-pyridinyl)amino]methylene]-1,1-bisphosphonate
  参考文献：
  名称：

  的新合成的官能化的芳基和吡啶基酸氨基亚甲基和它们的衍生物通过硅辅助方法

  摘要：

  通过硅辅助方法已经开发了新的方便的合成官能化的芳基和吡啶基氨基亚甲基双膦酸及其衍生物的方法。利用亚磷酸三（三甲基甲硅烷基）酯与N的独特反应，获得了含有吡啶部分的新功能化氨基亚甲基双膦酸-甲酰基氨基吡啶和三氟甲磺酸三甲基甲硅烷基酯在温和条件下作为催化剂。中间体–形成的四（三甲基甲硅烷基）氨基亚甲基双膦酸酯通过用过量甲醇进一步处理而转化为目标酸。相反，在氯化锌催化剂的存在下，在加热（130℃）下，将四种组分的混合物（亚磷酸二乙基三甲基甲硅烷基酯，原甲酸三乙基酯，芳基或吡啶基胺和亚磷酸二乙基酯）合成相应的四乙基氨基亚甲基双膦酸酯。提出并详细讨论了目标物质形成的催化方案。

  DOI：

  10.1016/j.jorganchem.2020.121177

文献信息

• Novel uses for drugs targeting glutamine synthetase
  申请人：NewThera

  公开号：EP1752143A1

  公开（公告）日：2007-02-14

  The present invention relates to novel therapeutic uses of tianeptine, salts, isomers, prodrugs, metabolites and structural analogs thereof. Furthermore, the present invention relates to the use of tianeptine, salts, isomers, pro-drugs, metabolites and structural analogs thereof, in obtaining methods of screening and of developing drugs. Finally, the present invention relates to the novel therapeutic use of other glutamine synthetase (GS) ligands and to the use of these ligands in obtaining methods for screening and developing drugs.

  本发明涉及噻奈普汀、其盐类、异构体、原药、代谢物和结构类似物的新型治疗用途。此外，本发明还涉及噻奈普汀、其盐类、异构体、原药、代谢物和结构类似物在获得药物筛选和开发方法中的用途。最后，本发明涉及其他谷氨酰胺合成酶（GS）配体的新型治疗用途，以及使用这些配体获得筛选和开发药物的方法。
• Advanced drug development and manufacturing
  申请人：Los Alamos National Security, LLC

  公开号：EP2511844A2

  公开（公告）日：2012-10-17

  There is described an apparatus for measuring protein characteristics comprising an X-ray fluorescence (XRF) spectrometer comprising a source of polychromatic X-rays, an X-ray detector, a protein, a molecule that has been exposed to and at least weakly binds to the protein, a plurality of X-ray fluorescence signal data obtained by irradiating chemical elements in the protein and molecule with the polychromatic X-rays and a security system for maintaining records for the data from the plurality of X-ray fluorescence signal measurements. There is also described an x-ray microscope for measuring a sample.

  描述了一种测量蛋白质特性的仪器，该仪器包括一个 X 射线荧光 (XRF) 光谱仪，其中包括一个多色 X 射线源、一个 X 射线探测器、一个蛋白质、一个已暴露于该蛋白质并至少与该蛋白质弱结合的分子、通过用多色 X 射线照射蛋白质和分子中的化学元素而获得的多个 X 射线荧光信号数据，以及一个用于维护多个 X 射线荧光信号测量数据记录的安全系统。此外，还介绍了一种用于测量样品的 X 射线显微镜。
• 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.
• PYRIDYLBISPHOSPHONATES FOR USE AS A THERAPEUTICAL AGENT
  申请人：LEIRAS OY

  公开号：EP0762883B1

  公开（公告）日：2001-11-14
• NOVEL USES FOR DRUGS TARGETING GLUTAMINE SYNTHETASE
  申请人：NewThera

  公开号：EP1965778A2

  公开（公告）日：2008-09-10