3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carboxamide | 347393-40-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carboxamide
• 英文别名: 3-(benzyloxy)-6-methyl-4-oxo-4H-pyran-2-carboxamide；6-Methyl-4-oxo-3-phenylmethoxypyran-2-carboxamide；6-methyl-4-oxo-3-phenylmethoxypyran-2-carboxamide
• CAS: 347393-40-2
• 化学式: C₁₄H₁₃NO₄
• 分子量: 259.262
• InChiKey: GATJJUIMQJWDDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  78.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carboxamide 在 盐酸 、 溶剂黄146 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 13.08h， 生成 3-hydroxy-6-methyl-2-(oxazol-2-yl)-4H-pyran-4-one
  参考文献：
  名称：

  Structure–Activity Relationships in Metal-Binding Pharmacophores for Influenza Endonuclease

  摘要：

  Metalloenzymes represent an important target space for drug discovery. A limitation to the early development of metalloenzyme inhibitors has been the lack of established structure-activity relationships (SARs) for molecules that bind the metal ion cofactor(s) of a metalloenzyme. Herein, we employed a bioinorganic perspective to develop an SAR for inhibition of the metalloenzyme influenza RNA polymerase PA(N) endonuclease. The identified trends highlight the importance of the electronics of the metal-binding pharmacophore (MBP), in addition to MBP sterics, for achieving improved inhibition and selectivity. By optimization of the MBPs for PA(N) endonuclease, a class of highly active and selective fragments was developed that displays IC50 values <50 nM. This SAR led to structurally distinct molecules that also displayed IC50 values of similar to 10 nM, illustrating the utility of a metal-centric development campaign in generating highly active and selective metalloenzyme inhibitors.

  DOI：

  10.1021/acs.jmedchem.8b01363
• 作为产物：
  描述：

  2-甲酰基-3-苄氧基-6-甲基-吡喃-4(1H)-酮 在 4-二甲氨基吡啶 、 sodium chlorite 、 氨基磺酸 、 氨 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 25.0h， 生成 3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carboxamide
  参考文献：
  名称：

  Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: novel iron chelators with enhanced pFe3+ values

  摘要：

  The synthesis of a range of 2-amido-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pKa values of the ligands together with the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of an amido substituent at the 2-position leads to an appreciable enhancement of the pFe(3+) values. The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a Fe-59-ferritin loaded rat model. The optimal effect was observed with the N-methyl amido derivative 15b, which has an associated pFe(3+) value of 21.7, more than two orders of magnitude higher than that of deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) 1a (pFe(3+) = 19.4). Dose response studies suggest that chelators with high pFe(3+) values scavenge iron more effectively at lower doses when compared with simple dialkyl substituted hydroxypyridinones. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00273-x

文献信息

• [EN] CYCLOALKYL DERIVATIVES OF 3-HYDROXY-4-PYRIDINONES<br/>[FR] DERIVES CYCLOALKYLE DE 3-HYDROXY-4-PYRIDINONES
  申请人：APOTEX INC

  公开号：WO2005049609A1

  公开（公告）日：2005-06-02

  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 R1 is X with the proviso that R2 is Y; or R1 is T with the proviso that R2 is W; or R1 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 C1 to C6 alkyl groups. X is C3-C6 cycloalkyl; Y is selected from the group consisting of C1 to C6 cycloalkyl; C1 to C6 alkyl, and C1 to C6 alkyl monosubstituted with a C3-C6 cycloalkyl; T is C1 to C6 alkyl; W is C3-C6 cycloalkyl; R3 is selected from the group consisting of hydrogen and C1 to C6 alkyl; R4 is selected from the group consisting of hydrogen and C1 to C6 alkyl; R5 is selected from the group consisting of hydrogen and C1 to C6 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。
• 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。
• 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。
• PROCESSES FOR THE MANUFACTURING OF 3-HYDROXY-N,1,6-TRIALKYL-4-OXO-1,4-DIHYDROPYRIDINE-2-CARBOXAMIDE
  申请人：APOTEX INC.

  公开号：EP1440061B1

  公开（公告）日：2007-04-11
• EP1687298A4
  申请人：——

  公开号：EP1687298A4

  公开（公告）日：2007-10-17