1-(2-pyridyl)ethane-1,2-bisphosphonate | 652989-80-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1-(2-pyridyl)ethane-1,2-bisphosphonate
• 英文别名: Phosphonic acid, [2-phosphono-1-(2-pyridinyl)ethyl]-；(2-phosphono-1-pyridin-2-ylethyl)phosphonic acid
• CAS: 652989-80-5
• 化学式: C₇H₁₁NO₆P₂
• 分子量: 267.115
• InChiKey: MOGYYGYIIWDQFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.9
• 重原子数：
  16
• 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：
  128
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  [2-(Diethoxy-phosphoryl)-2-pyridin-2-yl-ethyl]-phosphonic acid diethyl ester 在 盐酸 作用下， 以295 mg的产率得到1-(2-pyridyl)ethane-1,2-bisphosphonate
  参考文献：
  名称：

  Effects of Bisphosphonates on the Growth of Entamoeba histolytica and Plasmodium Species in Vitro and in Vivo

  摘要：

  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.

  DOI：

  10.1021/jm030084x

文献信息

• PROCESS FOR TREATING LAMENESS BY ADMINISTRATION OF A BISPHOSPHONIC ACID DERIVATIVE
  申请人：——

  公开号：US20010006960A1

  公开（公告）日：2001-07-05

  The invention relates to a process for treating lameness with an osseous, articular or osteoarticular component, comprising the administration, to a human or to an animal not suffering from arthritis or from fractures, of an effective amount of a bisphosphonic acid derivative of formula: 1 in which: R 1 represents a hydrogen atom, a halogen atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di(C 1 -C 4 )alkylamino; R 2 represents a halogen atom, a linear alkyl comprising from 1 to 5 carbon atoms which is unsubstituted or substituted with a group chosen from a chlorine atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di(C 1 -C 4 )alkylamino; a (C 3 -C 7 ) cycloalkylamino, or R 2 represents a phenoxy, a phenyl, a thiol, a phenylthio, a chlorophenylthio, a pyridyl, a pyridyl-methyl, a 1-pyridyl-1-hydroxymethyl, an imidazolyl-methyl or a 4-thiomorpholinyl, of one of its pharmaceutically acceptable salts or of one of its hydrates.

  本发明涉及一种治疗骨性、关节性或骨关节性跛足的方法，包括向人或未患关节炎或骨折的动物施用有效量的式（1）双膦酸衍生物： 1 其中 R 1 代表氢原子、卤素原子、羟基、氨基、单(C 1 -C 4 )烷基氨基或二(C 1 -C 4 )烷基氨基； R 2 代表卤素原子、由 1 至 5 个碳原子组成的线性烷基，该烷基未被取代或被选 自以下基团的基团取代：氯原子、羟基、氨基、单(C.1-C.4)烷基氨基、(C.1-C.4) 1 -C 4 )烷基氨基或二(C 1 -C 4)烷基氨基。 1 -C 4 )烷基氨基；一种(C 3 -C 7 )环烷基氨基、 或 R 2 代表苯氧基、苯基、硫醇、苯硫基、氯苯硫基、吡啶基、吡啶-甲基、1-吡啶-1-羟甲基、咪唑-甲基或 4-硫代吗啉基、 的一种药学上可接受的盐或其一种水合物。
• Process for increasing the egg production and strengthening the eggshells of poultry
  申请人：——

  公开号：US20030013685A1

  公开（公告）日：2003-01-16

  The present invention relates to a process for increasing the egg production and strengthening the eggshells of poultry, which comprises the administration to the animal of at least one bisphosphonic compound chosen from a bisphosphonic acid, a physiologically acceptable salt thereof, hydrates thereof and mixtures thereof.

  本发明涉及一种提高家禽产蛋量和增强蛋壳强度的工艺，包括向动物施用至少一种双膦化合物，该化合物选自双膦酸、其生理上可接受的盐、其水合物及其混合物。
• Process for treating lameness by administration of a bisphosphonic acid derivative
  申请人：Sanofi Sante Nutrition Animale

  公开号：US20030032627A1

  公开（公告）日：2003-02-13

  The invention relates to a process for treating lameness with an osseous, articular or osteoarticular component, comprising the administration, to a human or to an animal not suffering from arthritis or from fractures, of an effective amount of a bisphosphonic acid derivative of formula: 1 in which: R 1 represents a hydrogen atom, a halogen atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di(C 1 -C 4 ) alkylamino; R 2 represents a halogen atom, a linear alkyl comprising from 1 to 5 carbon atoms which is unsubstituted or substituted with a group chosen from a chlorine atom, a hydroxyl, an amino, a mono (C 1 -C 4 ) alkylamino or a di(C 1 -C 4 ) alkylamino; a (C 3 -C 7 ) cycloalkylamino, or R 2 represents a phenoxy, a phenyl, a thiol, a phenylthio, a chlorophenylthio, a pyridyl, a pyridyl-methyl, a 1-pyridyl-1-hydroxymethyl, an imidazolyl-methyl or a 4-thiomorpholinyl, of one of its pharmaceutically acceptable salts or of one of its hydrates.

  本发明涉及一种治疗骨性、关节性或骨关节性跛足的方法，包括向人或未患关节炎或骨折的动物施用有效量的式（1）双膦酸衍生物： 1 其中 R 1 代表氢原子、卤素原子、羟基、氨基、单(C 1 -C 4 )烷基氨基或二(C 1 -C 4 )烷基氨基； R 2 代表卤素原子、由 1 至 5 个碳原子组成的线性烷基，该烷基未被取代或被选 自以下基团的基团取代：氯原子、羟基、氨基、单（C 1 -C 4 烷基氨基或二(C 1 -C 4 )烷基氨基；一种(C 3 -C 7 环烷基氨基、 或 R 2 代表苯氧基、苯基、硫醇、苯硫基、氯苯硫基、吡啶基、吡啶-甲基、1-吡啶-1-羟甲基、咪唑-甲基或 4-硫代吗啉基、 的一种药学上可接受的盐或其一种水合物。
• Process for treating lameness administration of a bisphosphonic acid derivative
  申请人：Ceva Sante Animale

  公开号：US20040110726A1

  公开（公告）日：2004-06-10

  The invention relates to a process for treating lameness with an osseous, articular or osteoarticular component, comprising the administration, to a human or to an animal not suffering from arthritis or from fractures, of an effective amount of a bisphosphonic acid derivative of formula: 1 in which: R 1 represents a hydrogen atom, a halogen atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di (C 1 -C 4 ) alkylamino; R 2 represents a halogen atom, a linear alkyl comprising from 1 to 5 carbon atoms which is unsubstituted or substituted with a group chosen from a chlorine atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di (C 1 -C 4 )alkylamino; a (C 3 -C 7 ) cycloalkylamino, or R 2 represents a phenoxy, a phenyl, a thiol, a phenylthio, a chlorophenylthio, a pyridyl, a pyridyl-methyl, a 1-pyridyl-1-hydroxymethyl, an imidazolyl-methyl or a 4-thiomorpholinyl, of one of its pharmaceutically acceptable salts or of one of its hydrates.

  本发明涉及一种治疗骨性、关节性或骨关节性跛足的方法，包括向人或未患关节炎或骨折的动物施用有效量的式（1）双膦酸衍生物： 1 其中 R 1 代表氢原子、卤素原子、羟基、氨基、单(C 1 -C 4 )烷基氨基或二(C 1 -C 4 )烷基氨基； R 2 代表卤素原子、由 1 至 5 个碳原子组成的线性烷基，该烷基未被取代或被选 自以下基团的基团取代：氯原子、羟基、氨基、单(C 1 -C 4 )烷基氨基或二(C 1 -C 4 )烷基氨基；一种(C 3 -C 7 )环烷基氨基、 或 R 2 代表苯氧基、苯基、硫醇、苯硫基、氯苯硫基、吡啶基、吡啶-甲基、1-吡啶-1-羟甲基、咪唑-甲基或 4-硫代吗啉基、 的一种药学上可接受的盐或其一种水合物。
• Process for treating lameness with an osseous, articular or osteoarticular component in human or veterinary medicine, comprising the administration of a bisphosphonic acid derivative
  申请人：Du Mesnil Philippe

  公开号：US20060183717A1

  公开（公告）日：2006-08-17

  The invention relates to a process for treating lameness with an osseous, articular or osteoarticular component, comprising the administration, to a human or to an animal not suffering from arthritis or from fractures, of an effective amount of a bisphosphonic acid derivative of formula: in which: R 1 represents a hydrogen atom, a halogen atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di(C 1 -C 4 )alkylamino; R 2 represents a halogen atom, a linear alkyl comprising from 1 to 5 carbon atoms which is unsubstituted or substituted with a group chosen from a chlorine atom, a hydroxyl, an amino, a mono(C 1 -C 4 )alkylamino or a di(C 1 -C 4 )alkylamino; a (C 3 -C 7 )cycloalkylamino, or R 2 represents a phenoxy, a phenyl, a thiol, a phenylthio, a chlorophenylthio, a pyridyl, a pyridylmethyl, a 1-pyridyl-1-hydroxymethyl, an imidazolylmethyl or a 4-thiomorpholinyl, of one of its pharmaceutically acceptable salts or of one of its hydrates.

  本发明涉及一种治疗骨性、关节性或骨关节性跛足的方法，包括向人或未患关节炎或骨折的动物施用有效量的式双膦酸衍生物： 其中 R 1 代表氢原子、卤素原子、羟基、氨基、单(C 1 -C 4 )烷基氨基或二(C 1 -C 4 )烷基氨基； R 2 代表卤素原子、由 1 至 5 个碳原子组成的线性烷基，该烷基未被取代或被选 自以下基团的基团取代：氯原子、羟基、氨基、单(C.1-C.4)烷基氨基、(C.1-C.4) 1 -C 4 )烷基氨基或二(C 1 -C 4 )烷基氨基；一种(C 3 -C 7 )环烷基氨基、 或 R 2 代表苯氧基、苯基、硫醇、苯硫基、氯苯硫基、吡啶基、吡啶甲基、1-吡啶-1-羟甲基、咪唑甲基或 4-硫代吗啉基、其药学上可接受的盐之一或其水合物之一。