<2-(2-pyridylammonio)-1-phosphoryl>ethylphosphonate | 105462-22-4

• 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: <2-(2-pyridylammonio)-1-phosphoryl>ethylphosphonate
• 英文别名: 2-pyridylaminoethane-1,1-bisphosphonic acid；2-(pyridin-2-ylamino)ethylidene-1,1-bisphosphonic acid；[2-(pyridin-2-ylamino)ethane-1,1-diyl]bis(phosphonic acid)；[1-Phosphono-2-(pyridin-2-ylamino)ethyl]phosphonic acid
• CAS: 105462-22-4
• 化学式: C₇H₁₂N₂O₆P₂
• 分子量: 282.13
• InChiKey: BHVCADPDEFLLGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 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：

  环己胺 、 <2-(2-pyridylammonio)-1-phosphoryl>ethylphosphonate 以 水 为溶剂， 以60 mg的产率得到2-(pyridin-2-ylamino)ethylidene-1,1-bisphosphonic acid tricyclohexylammonium salt
  参考文献：
  名称：

  Tetrakis(trimethylsilyl) Ethenylidene-1,1-bisphosphonate: A Mild and Convenient Michael Acceptor for the Synthesis of 2-Aminoethylidene-1,1-bisphosphonic Acids and Their Potassium Salts

  摘要：

  通过胺对易于获得的四(三甲基硅基)乙烯叉二膦酸酯（H2C=C[P(O)(OTMS)2]2）进行迈克尔加成反应，实现了高度官能化的2-氨基亚甲基-1,1-双膦酸的直接合成。通过将迈克尔加成产物与氟化钾反应，也很容易以高产率获得标题化合物的钾盐。

  DOI：

  10.1055/s-0030-1260566
• 作为产物：
  描述：

  在 甲醇 作用下， 以170 mg的产率得到<2-(2-pyridylammonio)-1-phosphoryl>ethylphosphonate
  参考文献：
  名称：

  Tetrakis(trimethylsilyl) Ethenylidene-1,1-bisphosphonate: A Mild and Convenient Michael Acceptor for the Synthesis of 2-Aminoethylidene-1,1-bisphosphonic Acids and Their Potassium Salts

  摘要：

  通过胺对易于获得的四(三甲基硅基)乙烯叉二膦酸酯（H2C=C[P(O)(OTMS)2]2）进行迈克尔加成反应，实现了高度官能化的2-氨基亚甲基-1,1-双膦酸的直接合成。通过将迈克尔加成产物与氟化钾反应，也很容易以高产率获得标题化合物的钾盐。

  DOI：

  10.1055/s-0030-1260566

文献信息

• Reactions of vinylidenediphosphonic acid with nucleophiles
  作者：I. S. Alfer'ev、N. V. Mikhalin

  DOI：10.1007/bf00714446

  日期：1995.8

  It has been shown that heterocyclic amines can be added to the activated double bond of vinylidenediphosphonic acid to form adducts with betaine structures. Of aliphatic amines only trimethylamine reacts with vinylidenediphosphonic acid.

  已经表明杂环胺可以加到亚乙烯基二膦酸的活化双键上以形成具有甜菜碱结构的加合物。在脂肪胺中，只有三甲胺与亚乙烯基二膦酸反应。
• [EN] METHODS FOR THE TREATMENT OF OSTEOPOROSIS USING BONE ACTIVE PHOSPHONATES AND PARATHYROID HORMONE<br/>[FR] PROCEDES DE TRAITEMENT DE L'OSTEOPOROSE UTILISANT DES PHOSPHONATES OSTEOACTIFS ET UNE HORMONE PARATHIROÏDIENNE
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：WO1996007417A1

  公开（公告）日：1996-03-14

  (EN) The present invention provides methods of treating a human or other animal subject having a bone metabolism disorder, comprising the steps of: (a) administering to said subject a safe and effective amount of a bone active phosphonate during a period of at least about 6 months; (b) administering to said subject a safe and effective amount of a parathyroid hormone, during a period of from about 3 to about 12 months.(FR) L'invention concerne des procédés de traitement d'un sujet humain ou d'un sujet animal présentant un dérèglement du métabolisme osseux, comprenant les étapes consistant: (a) à administrer audit sujet une dose efficace et sans danger d'un phosphonate ostéoactif pendant une durée d'au moins environ 6 mois, (b) à administrer audit sujet une dose efficace et sans danger d'une hormone parathyroïdienne, pendant une durée comprise entre environ 3 et environ 12 mois.

  本发明提供了治疗骨代谢紊乱的人类或其他动物受试者的方法，包括以下步骤：（a）在至少约6个月的时间内向该受试者施用安全有效量的骨活性膦酸盐；（b）在约3至约12个月的时间内向该受试者施用安全有效量的甲状旁腺激素。
• Kit containing polyphosphonate for treating osteoporosis
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0210728A2

  公开（公告）日：1987-02-04

  Amethodfortreating or preventing osteoporosis utilizing a cyclic regimen comprising alternating for two or more cyclesthe administration of a bone resorption inhibiting polyphosphonate and a no treatment (rest) period. Further disclosed is a kit for use in implementing this method of treatment.

  一种利用循环疗法治疗或预防骨质疏松症的方法，该疗法包括在两个或两个以上的周期内交替服用抑制骨吸收的多膦酸盐和一个无治疗（休息）期。还公开了一种用于实施这种治疗方法的试剂盒。
• Skin penetration system for salts of amine-functional drugs
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0351897A2

  公开（公告）日：1990-01-24

  The invention involves pharmaceutical compositions for topical application comprising: (a) a pharmaceutically-acceptable salt of addition of an amine-functional drug (other than opioid analgesic drugs); (b) a C₇ to C₂₂ straight-chain or branched-chain, saturated or unsaturated, fatty acid having a melting point of less than about 50°C; and (c) a C₃-C₄ alkane diol.

  本发明涉及用于局部应用的药物组合物，包括 (a) 一种胺功能药物（阿片类镇痛药除外）的药学上可接受的加成盐； (b) C₇ 至 C₂₂ 直链或支链、饱和或不饱和脂肪酸，熔点低于约 50°C；以及 (c) C₃-C₄ 烷二醇。
• 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.