1-cyclopropyl-3-hydroxy-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid methylamide | 887774-94-9

• 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-cyclopropyl-3-hydroxy-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid methylamide
• 英文别名: 2-Pyridinecarboxamide, 1-cyclopropyl-1,4-dihydro-3-hydroxy-N,6-dimethyl-4-oxo-；1-cyclopropyl-3-hydroxy-N,6-dimethyl-4-oxopyridine-2-carboxamide
• CAS: 887774-94-9
• 化学式: C₁₁H₁₄N₂O₃
• 分子量: 222.244
• InChiKey: GYWMPYYHESRUBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  iron(III) chloride 、 1-cyclopropyl-3-hydroxy-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid methylamide 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 144.0h， 以66%的产率得到Fe(Apo6619)3
  参考文献：
  名称：

  [EN] CYCLOALKYL DERIVATIVES OF 3-HYDROXY-4-PYRIDINONES
  [FR] DERIVES CYCLOALKYLE DE 3-HYDROXY-4-PYRIDINONES

  摘要：

  本发明提供了一种3-羟基-4-吡啶酮的环烷基衍生物，可用于螯合金属离子，如铁。描述了其制备和用途。特别是，本发明涉及化学和生物系统中铁的去除，包括具有式（I）的螯合剂；其中R1是X，但R2是Y；或R1是T，但R2是W；或R1是X，但R2R5N在一起形成从哌啶基，吗啉基，吡咯烷基或哌嗪基中选择的杂环环，其中哌啶基，吗啉基，吡咯烷基或哌嗪基的基团是未取代或用1至3个C1至C6烷基取代。X是C3-C6环烷基；Y选自由C1至C6环烷基；C1至C6烷基和C1至C6烷基单取代的C3-C6环烷基；T是C1至C6烷基；W是C3-C6环烷基；R3选自氢和C1至C6烷基的群；R4选自氢和C1至C6烷基的群；R5选自氢和C1至C6烷基的群；以及其药学上可接受的盐。这些化合物的制药组合物可用于从铁过载病患者中去除体内过量的铁。

  公开号：

  WO2005049609A1
• 作为产物：
  描述：

  3-benzyloxy-1-cyclopropyl-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid methylamide 在 10% Pd(OH)2/C 氢气 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 1-cyclopropyl-3-hydroxy-6-methyl-4-oxo-1,4-dihydro-pyridine-2-carboxylic acid methylamide
  参考文献：
  名称：

  [EN] CYCLOALKYL DERIVATIVES OF 3-HYDROXY-4-PYRIDINONES
  [FR] DERIVES CYCLOALKYLE DE 3-HYDROXY-4-PYRIDINONES

  摘要：

  本发明提供了一种3-羟基-4-吡啶酮的环烷基衍生物，可用于螯合金属离子，如铁。描述了其制备和用途。特别是，本发明涉及化学和生物系统中铁的去除，包括具有式（I）的螯合剂；其中R1是X，但R2是Y；或R1是T，但R2是W；或R1是X，但R2R5N在一起形成从哌啶基，吗啉基，吡咯烷基或哌嗪基中选择的杂环环，其中哌啶基，吗啉基，吡咯烷基或哌嗪基的基团是未取代或用1至3个C1至C6烷基取代。X是C3-C6环烷基；Y选自由C1至C6环烷基；C1至C6烷基和C1至C6烷基单取代的C3-C6环烷基；T是C1至C6烷基；W是C3-C6环烷基；R3选自氢和C1至C6烷基的群；R4选自氢和C1至C6烷基的群；R5选自氢和C1至C6烷基的群；以及其药学上可接受的盐。这些化合物的制药组合物可用于从铁过载病患者中去除体内过量的铁。

  公开号：

  WO2005049609A1

文献信息

• Cycloalkyl derivatives of 3-hydroxy-4-pyridinones field of the invention
  申请人：Tam Fat Tim

  公开号：US20070082904A1

  公开（公告）日：2007-04-12

  The present invention provides an cycloalkyl derivative of 3-hydroxy-4-pyridinone which is useful for the chelation of metal ions such as iron. Its preparation and use is described. In particular, the invention concerns the removal of iron in chemical and biological systems including chelating agents having the formula (I); wherein R 1 is X with the proviso that R 2 is y; or R 1 is T with the proviso that R 2 is W; or R 1 is X with the proviso that R 2 R 5 N when taken together form a heterocyclic ring selected from piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl, wherein the group piperidinyl, morphoninyl, pyrrolidinyl or piperazinyl is either unsubstituted or substituted with one to three C 1 to C 6 alkyl groups. X is C 3 -C 6 cycloalkyl; Y is selected from the group consisting of C, to C 6 cycloalkyl; C 1 to C 6 alkyl, and C 1 to C 6 alkyl monosubstituted with a C 3 -C 6 cycloalkyl; T is C 1 to C 6 alkyl; W is C 3 -C 6 cycloalkyl; R 3 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; R 4 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; R 5 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; and its pharmaceutically acceptable salt thereof. Pharmaceutical compositions of such compounds are useful in the removal of excess body iron from patients with iron overload diseases.

  本发明提供了3-羟基-4-吡啶酮的环烷基衍生物，可用于螯合金属离子，如铁离子。描述了其制备和用途。特别是，本发明涉及化学和生物系统中铁的去除，包括具有式（I）的螯合剂，其中R1为X，但R2为y；或R1为T，但R2为W；或R1为X，但R2R5N在一起形成从哌啶基，吗啉基，吡咯烷基或哌嗪基中选择的杂环环，其中哌啶基，吗啉基，吡咯烷基或哌嗪基的基团是未取代的或用1至3个C1至C6烷基基团取代的。X为C3-C6环烷基；Y选自由C到C6环烷基；C1到C6烷基和C1到C6烷基单取代的C3-C6环烷基；T为C1到C6烷基；W为C3-C6环烷基；R3选自氢和C1到C6烷基的群；R4选自氢和C1到C6烷基的群；R5选自氢和C1到C6烷基的群；以及其药学上可接受的盐。这些化合物的制药组合物可用于治疗铁过载病患者的体内多余铁的去除。
• Process For The Manufacture Of 3-Hydroxy-N-Alkyl-1-Cycloalkyl-6-Alkyl-4-Oxo-1,4-Dihydropyridine-2-Carboxamide And Its Related Analogues
  申请人：Tam Fat Tim

  公开号：US20080096886A1

  公开（公告）日：2008-04-24

  The present invention relates to a novel process for the preparation of 1-alkyl or 1-cycloalkyl derivatives of 3-hydroxy-4-oxo-1,4-dihydropyridine-2-carboxamide of formula I. The process includes reacting an amine R 2 NH 2 with a compound of formula II in a solution of metal hydroxide in water to give a compound of formula III. Subsequent reaction of the compound of formula III with an acid chloride formation reagent in an inert solvent gives compounds of formula I. The acid chloride formation reagent is selected from oxalyl chloride and dimethylformamide, dimethylchloromethylene-ammonium chloride and thionyl chloride and dimethylformamide. If desired, a compound of formula I where R 5 is hydrogen may be formed when an intermediate substituent is used wherein R 5 is an alcohol protective group removable by catalytic hydrogenation.

  本发明涉及一种新型方法，用于制备式I的1-烷基或1-环烷基的3-羟基-4-氧代-1,4-二氢吡啶-2-羧酰胺衍生物。该方法包括将胺R2NH2与式II的化合物在水中的金属氢氧化物溶液中反应，以得到式III的化合物。随后，在惰性溶剂中使用酸氯化物形成试剂与式III的化合物反应，得到式I的化合物。酸氯化物形成试剂选自草酰氯和二甲基甲酰胺、二甲基氯甲基胺盐酸盐和亚磺酰氯和二甲基甲酰胺。如果需要，当使用中间体取代基时，可以形成式I的化合物，其中R5为氢，R5是通过催化氢化可去除的醇保护基。
• Cycloalkyl derivatives of 3-hydroxy-4-pyridinones
  申请人：Tam Tim Fat

  公开号：US20090170850A1

  公开（公告）日：2009-07-02

  The present invention provides an cycloalkyl derivative of 3-hydroxy-4-pyridinone which is useful for the chelation of metal ions such as iron. Its preparation and use is described. In particular, the invention concerns the removal of iron in chemical and biological systems including chelating agents having the formula I wherein R 1 is X with the proviso that R 2 is Y; or R 1 is T with the proviso that R 2 is W; or R 1 is X with the proviso that R 2 R 5 N when taken together form a heterocyclic ring selected from piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl, wherein the group piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl is either unsubstituted or substituted with one to three C 1 to C 6 alkyl groups. X is C 3 -C 6 cycloalkyl; Y is selected from the group consisting of C 1 to C 6 cycloalkyl; C 1 to C 6 alkyl, and C 1 to C 6 alkyl monosubstituted with a C 3 -C 6 cycloalkyl; T is C 1 to C 6 alkyl; W is C 3 -C 6 cycloalkyl; R 3 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; R 4 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; R 5 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; and its pharmaceutically acceptable salt thereof. Pharmaceutical compositions of such compounds are useful in the removal of excess body iron from patients with iron overload diseases.

  本发明提供了3-羟基-4-吡啶酮的环烷基衍生物，可用于螯合金属离子，如铁离子。描述了其制备和使用。具体而言，本发明涉及在化学和生物系统中除铁，包括具有式I的螯合剂，其中R1是X，但R2是Y；或R1是T，但R2是W；或R1是X，但R2和R5N在一起形成从哌啶基，吗啡啉基，吡咯烷基或哌嗪基中选择的杂环环，其中哌啶基，吗啡啉基，吡咯烷基或哌嗪基的基团是未取代或用一到三个C1到C6烷基基团取代。X是C3-C6环烷基；Y选自由C1到C6环烷基；C1到C6烷基；和用C3-C6环烷基单取代的C1到C6烷基。T是C1到C6烷基；W是C3-C6环烷基；R3选自氢和C1到C6烷基的群；R4选自氢和C1到C6烷基的群；R5选自氢和C1到C6烷基的群；以及其药学上可接受的盐。这些化合物的制药组合物对于从铁过载病患者中去除过量体内铁非常有用。
• Methods and compositions for treating bacterial infections with iron chelators
  申请人：Zurawski Daniel

  公开号：US10064858B2

  公开（公告）日：2018-09-04

  The present invention provides methods and compositions for treating or preventing bacterial infections, where a pharmaceutically acceptable iron chelator that reduces biological availability of iron for one or more strains of bacteria, such as VK28 or an analog or derivative thereof is administered to a patient in need of treatment. The method also provides methods and compositions where an iron chelator and an antibiotic are administered to a patient in need of treatment for a bacterial infection.

  本发明提供了治疗或预防细菌感染的方法和组合物，其中向需要治疗的患者施用一种药学上可接受的铁螯合剂，该螯合剂可降低一种或多种菌株铁的生物可用性，如VK28或其类似物或衍生物。该方法还提供了向需要治疗细菌感染的患者施用铁螯合剂和抗生素的方法和组合物。
• EP1687298A4
  申请人：——

  公开号：EP1687298A4

  公开（公告）日：2007-10-17