1-hydroxy-2-(2-pyridinyl)ethylidenebisphosphonic acid monosodium | 334708-63-3

• 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-2-(2-pyridinyl)ethylidenebisphosphonic acid monosodium
• 英文别名: risedronate sodium；1-Hydroxy-2-(2-pyridyl)ethane-1,1-diphosphonic acid monosodium salt；sodium;hydroxy-(1-hydroxy-1-phosphono-2-pyridin-2-ylethyl)phosphinate
• CAS: 334708-63-3
• 化学式: C₇H₁₀NO₇P₂*Na
• 分子量: 305.096
• InChiKey: VJJUOVKYUVGIFX-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -4.0
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  151
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  P,P'-[1-羟基-2-(2-吡啶基)亚乙基]二膦酸 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.0h， 生成 1-hydroxy-2-(2-pyridinyl)ethylidenebisphosphonic acid monosodium
  参考文献：
  名称：

  Microwave-assisted efficient synthesis of bisphosphonate libraries: a useful procedure for the preparation of bisphosphonates containing nitrogen and sulfur

  摘要：

  Microwave-assisted rapid and efficient procedure for the synthesis of bisphosphonate and their libraries is described in solvent-free medium. Bisphosphonates having nitrogen and sulfur are synthesized following this new procedure. This procedure is simple and can be useful for the generation of compound libraries of a class of bone-resorptive inhibitors such as N- and N-, S- containing bisphosphonates.

  DOI：

  10.1007/s00044-012-0153-4

文献信息

• 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。
• 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：EP0646119B1

  公开（公告）日：1998-07-15
• US5391743A
  申请人：——

  公开号：US5391743A

  公开（公告）日：1995-02-21
• [EN] QUATERNARY NITROGEN-CONTAINING PHOSPHONATE COMPOUNDS FOR TREATING ABNORMAL CALCIUM AND PHOSPHATE METABOLISM AS WELL AS DENTAL CALCULUS AND PLAQUE<br/>[FR] COMPOSES QUATERNAIRES DE PHOSPHONATE CONTENANT DE L'AZOTE ET SERVANT A TRAITER LE METABOLISME ANORMAL DU CALCIUM ET DU PHOSPHATE AINSI QUE LE TARTRE ET LA PLAQUE DENTAIRE
  申请人：PROCTER & GAMBLE PHARMACEUTICALS, INC.

  公开号：WO1993024498A1

  公开（公告）日：1993-12-09

  (EN) The present invention relates to quaternary nitrogen-containing phosphonate compounds, and the pharmaceutically-acceptable salts and esters thereof and having general structure (I). The present invention further relates to pharmaceutical compositions containing a safe and effective amount of a compound of the present invention, and pharmaceutically-acceptable excipients. Finally, the present invention relates to methods for treating or preventing pathological conditions characterized by abnormal calcium and phosphate metabolism such as osteoporosis, rheumatoid arthritis, and osteoarthritis in humans or other mammals and to methods for treating or preventing dental calculus, plaque and gingivitis. This method comprises administering to a human or other mammal in need of such treatment a safe and effective amount of a compound or composition of the present invention.(FR) L'invention se rapporte à des composés quaternaires de phosphonate contenant de l'azote, ainsi qu'à leur sels et esters acceptables pharmaceutiquement, représentés par la formule (I). L'invention se rapporte, de plus, à des compositions pharmaceutiques contenant une quantité efficace et sans danger d'un composé décrit par l'invention, ainsi que des excipients acceptables pharmaceutiquement. Enfin, l'invention se rapporte à des procédés de traitement ou de prévention d'états pathologiques caractérisés par un métabolisme anormal du calcium et du phosphate, tels que l'ostéoporose, la polyarthrite rhumatoïde et l'ostéoarthtrite chez l'homme ou d'autres mammifères, ainsi qu'à des procédés de traitement ou de prévention du tartre dentaire, de la plaque dentaire et de la gengivite. Le procédé comprend l'administration à l'homme ou à un autre mammifère d'une quantité efficace et sans danger d'un composé ou d'une composition décrit par l'invention.
• Microwave-assisted efficient synthesis of bisphosphonate libraries: a useful procedure for the preparation of bisphosphonates containing nitrogen and sulfur
  作者：Racha Lenin、Rallabandi Madusudan Raju、Divvela V. N. Srinivasa Rao、Uttam Kumar Ray

  DOI：10.1007/s00044-012-0153-4

  日期：2013.4

  Microwave-assisted rapid and efficient procedure for the synthesis of bisphosphonate and their libraries is described in solvent-free medium. Bisphosphonates having nitrogen and sulfur are synthesized following this new procedure. This procedure is simple and can be useful for the generation of compound libraries of a class of bone-resorptive inhibitors such as N- and N-, S- containing bisphosphonates.