1-hydroxy-3-(3-pyridyl)propylidene-1,1-bisphosphonic acid | 104261-69-0

• 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: 1-hydroxy-3-(3-pyridyl)propylidene-1,1-bisphosphonic acid
• 英文别名: 3-(3-pyridyl)-1-hydroxy-propane-1,1-bisphosphonate；[1-Hydroxy-3-(3-pyridinyl)propylidene]bis[phosphonic acid]；[1-Hydroxy-3-(pyridin-3-yl)propane-1,1-diyl]bis(phosphonic acid)；(1-hydroxy-1-phosphono-3-pyridin-3-ylpropyl)phosphonic acid
• CAS: 104261-69-0
• 化学式: C₈H₁₃NO₇P₂
• 分子量: 297.141
• InChiKey: ILROXFQHACCDLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.8
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  148
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-hydroxy-3-(3-pyridyl)propylidene-1,1-bisphosphonic acid 、 碘甲烷 在 丙酮 、 乙醇 、 水 作用下， 以 sodium hydroxide 、 水 、 乙醇 为溶剂， 反应 16.0h， 以to yield 0.5 g of 3-(3-hydroxy-3,3-diphosphono-propyl)-1-methyl pyridinium hydroxide, inner salt的产率得到[1-羟基-3-(1-甲基吡啶-1-鎓-3-基)-1-膦酰丙基]膦酸氢氧化物
  参考文献：
  名称：

  Quaternary nitrogen-containing phosphonate compounds, pharmaceutical

  摘要：

  本发明涉及含四元氮磷酸盐化合物及其药学上可接受的盐和酯，其具有以下通式：##STR1## 其中：Z是饱和、不饱和或芳香的单环或多环碳环或单环或多环杂环，其中包含一个或多个从O、S或N中选择的杂原子；Y是N.sup.+（R.sup.8）.sub.2或C（R.sup.1）.sub.2，当Y是C（R.sup.1）.sub.2时，至少有一个R.sup.2必须为N.sup.+（R.sup.8）.sub.3；R.sup.1、R.sup.2、R.sup.5和R.sup.8在权利要求1中定义，m和n为0到10的整数；m+n为0到10；R为COOH；PO.sub.3 H.sub.2；SO.sub.3 H；或P（O）（OH）R.sub.4，其中R.sub.4为1-8个碳原子的取代或未取代的烷基。本发明还涉及含有本发明化合物的安全有效量的药物组合物和药学上可接受的辅料。最后，本发明涉及用于治疗或预防人类或其他哺乳动物中的异常钙和磷代谢的病理状况，如骨质疏松症、类风湿性关节炎和骨关节炎，以及用于治疗或预防牙石、菌斑和牙龈炎的方法。

  公开号：

  US05770586A1
• 作为产物：
  描述：

  3-(3-吡啶基)丙酸 在 亚磷酸 、 三氯化磷 、 水 作用下， 生成 1-hydroxy-3-(3-pyridyl)propylidene-1,1-bisphosphonic acid
  参考文献：
  名称：

  Bisphosphonates Inhibit the Growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum:  A Potential Route to Chemotherapy

  摘要：

  We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC50 activity values against parasite replication (e.g. o-risedronate, IC50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.

  DOI：

  10.1021/jm0002578

文献信息

• Pharmaceutical compositions containing geminal diphosphonates
  申请人：THE PROCTER & GAMBLE COMPANY

  公开号：EP0186405A2

  公开（公告）日：1986-07-02

  Pharmaceutical compositions, useful for treating abnormal calcium and phosphate metabolism, which contain geminal-diphosphonic acid compounds; and a method of treating diseases characterized by abnormal calcium and phosphate metabolism utilizing these pharmaceutical compositions.

  用于治疗钙和磷酸盐代谢异常的药物组合物，其中含有宝石二膦酸化合物；以及利用这些药物组合物治疗以钙和磷酸盐代谢异常为特征的疾病的方法。
• Quaternary nitrogen-containing phosphonate compounds for treating abnormal calcium and phosphate metabolism as well as dental calculus and plaque
  申请人：Procter & Gamble Pharmaceuticals, Inc.

  公开号：EP0849272A1

  公开（公告）日：1998-06-24

  1. Quaternary nitrogen-containing phosphonates which are useful in treating or prevening disorders of abnormal calcium and phosphate metabolism and the pharmaceutically-acceptable salts and esters thereof, characterised in that they have the general structure: wherein m and n are integers from 0 to 10; m + n is from 0 to 10; (a) Q is a covalent bond or a moiety selected from O, S, NR1; (b) Y is N+(R8)2 or C(R1)2, and when Y is C(R1)2, at least one R2 must be N+(R8)3; (c) Z is a five-membered saturated, unsaturated, or aromatic, monocyclic carbocycle or heterocycle containing one heteroatom, wherein the heteroatom is nitrogen, (d) R is COOH, SO3H,PO3H2 or P(O)(OH)R4, wherein R4 is alkyl of 1-8 carbon atoms, preferably PO3H2; (e) each R1 is selected from SR6; R9SR6; hydrogen, hydroxy; C1-C8 alkyl; -OR3; -CO2R3; -O2CR3; -NR32; -N(R3)C(O)R3, -C(O)N(R3)2; halogen; -C(O)R3; arylalkyl; nitro; aryl, and combinations thereof, preferably SR6, R9SR6, hydrogen, C1-C8 alkyl, - NR3 2 or CO2R3; (f) each R2 is one or more substituents on the Z moiety independently selected from N+(R8)3; SR6; R9SR6; hydrogen; C1-C8 alkyl; -OR3; -CO2R3; -O2CR3; -NR32;-N(R3)C(O)R3; -C(O)N(R3)2; halogen; hydroxy; -C(O)R3; arylalkyl; nitro; aryl, preferably N+(R8)3, SR6, R9SR6, hydrogen, C1-C8 alkyl; -NR3 2, -OR3, -CO2R3; (g) each R1 is independently selected from hydrogen, alkyl having from 1-8 carbon atoms, and R9SR6, preferably hydrogen, R9SR6 or C1-C8 alkyl. (h) R1 is selected from hydrogen; halogen; SR6; R9SR6, amino; hydroxy; and C1-C8 alkyl, preferably hydrogen, SR6; R9SR6; (i) each R6 is independently selected from H; -C(O)R7;-C(S)R7; -C(O)NR72; -C(S)N(R7)2; -C(S)OR7; -C(O)OR7; wherein R7 is hydrogen or C1-C8 alkyl, preferably hydrogen, -C(O)R7, -C(S)R7; (j ) each R8 is independently selected from nil, alkyl having 1-35 carbon atoms, phenyl, benzyl, or R9 SR6; preferably alkyl having 1-35 carbon atoms; (k) R9 is C1-C8 alkyl.

  1.有助于治疗或预防钙和磷酸盐代谢异常紊乱的含季氮的膦酸盐及其药学上可接受的盐和酯，其特征在于它们具有一般结构： 其中 m 和 n 为 0 至 10 的整数；m + n 为 0 至 10； (a) Q 是共价键或选自 O、S、NR1 的分子； (b) Y 是 N+(R8)2 或 C(R1)2，当 Y 是 C(R1)2 时，至少一个 R2 必须是 N+(R8)3； (c) Z 是含有一个杂原子的五元饱和、不饱和或芳香单环碳环或杂环，其中杂原子为氮、 (d) R 是 COOH、SO3H、PO3H2 或 P(O)(OH)R4，其中 R4 是 1-8 个碳原子的烷基，最好是 PO3H2； (e) 每个 R1 选自 SR6、R9SR6、氢、羟基、C1-C8 烷基、-OR3、-CO2R3、-O2CR3、-NR32、-N(R3)C(O)R3、-C(O)N(R3)2、卤素、-C(O)R3、芳烷基、硝基、芳基及其组合，优选 SR6、R9SR6、氢、C1-C8 烷基、-NR3 2 或 CO2R3； (f) 每个 R2 是 Z 分子上的一个或多个取代基，独立选自 N+(R8)3；SR6；R9SR6；氢；C1-C8 烷基；-OR3；-CO2R3；-O2CR3；-NR32；-N(R3)C(O)R3；-C(O)N(R3)2；卤素；羟基；-C(O)R3；芳烷基；硝基；芳基，优选 N+(R8)3、SR6、R9SR6、氢、C1-C8 烷基；-NR3 2、-OR3、-CO2R3； (g) 每个 R1 独立地选自氢、具有 1-8 个碳原子的烷基和 R9SR6，优选氢、R9SR6 或 C1-C8 烷基。 (h) R1 选自氢、卤素、SR6、R9SR6、氨基、羟基和 C1-C8 烷基，优选氢、SR6、R9SR6； (i) 每个 R6 独立选自 H；-C(O)R7；-C(S)R7；-C(O)NR72；-C(S)N(R7)2；-C(S)OR7；-C(O)OR7；其中 R7 是氢或 C1-C8 烷基，优选氢、-C(O)R7、-C(S)R7； (j) 每个 R8 独立选自零、具有 1-35 个碳原子的烷基、苯基、苄基或 R9 SR6；优选具有 1-35 个碳原子的烷基； (k) R9 是 C1-C8 烷基。
• POLISHING COMPOSITION, POLISHING METHOD USING SAME, AND METHOD FOR PRODUCING SEMICONDUCTOR DEVICE
  申请人：Fujimi Incorporated

  公开号：EP2693460A1

  公开（公告）日：2014-02-05

  The polishing composition of the present invention contains an oxidizing agent and a scratch-reducing agent represented by general formula (1) or (2) below. In the formulas, X1 and X2 are each independently a hydrogen atom, a hydroxyl group, a carboxyl group, a phosphate group, an alkyl group, an aryl group, an alkyl polyamine group, an alkyl polyphosphate group, an alkyl polycarboxylate group, an alkyl polyaminopolyphosphate group, or an alkyl polyaminopolycarboxylate group.

  本发明的抛光组合物含有一种氧化剂和一种划痕还原剂，由以下通式（1）或（2）表示。 在这些通式中，X1 和 X2 各自独立地为氢原子、羟基、羧基、磷酸基、烷基、芳基、烷基多胺基、烷基多磷酸基、烷基多羧酸基、烷基多胺多磷酸基或烷基多胺多羧酸基。
• Bisphosphonates Inhibit the Growth of <i>Trypanosoma </i><i>b</i><i>rucei</i>, <i>Trypanosoma </i><i>c</i><i>ruzi</i>, <i>Leishmania </i><i>d</i><i>onovani</i>, <i>Toxoplasma </i><i>g</i><i>ondii</i>, and <i>Plasmodium </i><i>f</i><i>alciparum</i>:  A Potential Route to Chemotherapy
  作者：Michael B. Martin、Joshua S. Grimley、Jared C. Lewis、Huel T. Heath、Brian N. Bailey、Howard Kendrick、Vanessa Yardley、Aura Caldera、Renee Lira、Julio A. Urbina、Silvia N. J. Moreno、Roberto Docampo、Simon L. Croft、Eric Oldfield

  DOI：10.1021/jm0002578

  日期：2001.3.1

  We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC50 activity values against parasite replication (e.g. o-risedronate, IC50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.
• Neue Diphosphonsäurederivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel
  申请人：BOEHRINGER MANNHEIM GMBH

  公开号：EP0170228B1

  公开（公告）日：1988-12-28